JP2004325265A

JP2004325265A - Method and apparatus for analyzing polymer

Info

Publication number: JP2004325265A
Application number: JP2003120759A
Authority: JP
Inventors: Hiroaki Sato; 浩昭佐藤; Hiroaki Tao; 博明田尾; Nobuyuki Ichieda; 信之市枝; Hajime Otani; 肇大谷; Keigo Aoi; 啓悟青井
Original assignee: National Institute of Advanced Industrial Science and Technology AIST
Current assignee: National Institute of Advanced Industrial Science and Technology AIST
Priority date: 2003-04-24
Filing date: 2003-04-24
Publication date: 2004-11-18
Anticipated expiration: 2023-04-24
Also published as: JP3837543B2

Abstract

<P>PROBLEM TO BE SOLVED: To provide a method and an apparatus for measuring the absolute molecular weight distribution, absolute molecular weight, which comprises a combination of size exclusion chromatography and mass spectrometry, and which is unaffected by the effects caused by the diffusion of a sample in a flow path in size exclusion chromatographic separation, the interaction between a filler and a sample in a separation column, or the like. <P>SOLUTION: A polymer sample is separated and dispensed by size exclusion chromatography. A peak intensity in a mass spectrum obtained by performing mass spectrometry on each fraction is corrected on the basis of the detector signal intensity of size exclusion chromatography observed for the corresponding fraction. <P>COPYRIGHT: (C)2005,JPO&NCIPI

Description

【０００１】
【発明の属する技術分野】
本発明は、高分子重合物の分析方法及び分析装置、更に詳しくは、高分子重合物の絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成を測定する方法及び分析装置に関する。
【０００２】
【従来の技術】
高分子重合物は、単一成分あるいは複数のモノマー成分が重合して得られるものである。この高分子化合物を構成する成分に応じて、高分子化合物の分子量はある特定の範囲をもって分子量が表現される。例えば、ポリエチレンであれば、特定の分子量のものが何パーセント、特定の分子量のものが何パーセントというように分子量に応じてその組成割合が表現され、その分布として分子量は表される。また、複数のモノマー、例えば、アクリルニトリルとブタジエンからなる共重合体であれば、構成するアクリルニトリルとブタジエンについて、分子量に応じて組成割合に応じた分子量の数値が算出され、表現され、数平均分子量或いは重量平均分子量などの平均分子量又は分子量分布として表現される。その起源により重合物は、天然高分子重合物と合成高分子重合物に大別されるが、分子量については平均分子量或いは分子量分布として表現されることに関しては、同じである。このように、高分子重合物は、その合成過程における統計的偶然性によって分子量分布をもっており、このことは高分子重合物の各種性質・特性に大きく影響するため、その平均分子量及び分子量分布を正確に測定することは、高分子重合物の特性を把握し、品質管理、性能評価等を行う上で非常に重要である。そのために、分子量の測定方法は、いろいろと検討されてきた。
【０００３】
従来、高分子重合物の平均分子量及び分子量分布を比較的簡単に測定する方法として、ＳＥＣを利用されている。ＳＥＣを用いる場合には、高分子重合物を溶解した試料溶液として、細孔をもつゲル状の充填剤を充填した分離カラムを通過させると、充填剤は、分子量（サイズ）の小さな部分に関しては、ゲルの細孔内部に入り込みやすいが分子量（サイズ）の大きな部分はゲルの細孔内部に入り込みにくい性質があるので、高分子重合体は充填剤中に取り込まれる状態が相違する。取込まれた高分子化合物を溶出させようとする場合には、分子サイズが小さいほど分離カラムから溶出する時間が遅れる結果となる。この現象を利用して、分離カラムで分子サイズごとに分離された成分を、示差屈折検出器（以下、ＲＩ検出器という）や紫外可視分光検出器（以下、ＵＶ検出器という）などを用いて検出することによってクロマトグラムを観測する。このようにして分子量に応じた分布を調べることができる。
高分子重合物の分子量分布は、ＳＥＣにより観測されたクロマトグラムから解析することができるが、そのクロマトグラムは、ＳＥＣ装置の流路内での試料の拡散現象、分離カラム内の充填剤及びその細孔のサイズ分布、充填剤や流路を構成する材料と試料との間に生じる吸着あるいは反発などの相互作用など不可避の様々な要因により大きく影響を受け、しかも、その影響の度合いは、高分子重合物の種類、分子量、分子量分布、濃度などによって異なるとされている（非特許文献１）。そのため、上記の要因による影響を可能な限り低減することが重要であり、該技術分野では、ＳＥＣの移動相溶媒の種類を検討することにより（特許文献１、特許文献２、特許文献３、特許文献４、特許文献５、特許文献６）、又は検量線の作成方法（特許文献７）などの検討を行って、前記の低減が行われてきた。しかしながら、これらの方法では、上記要因を完全に打ち消すことは困難であるうえに、下記の理由により、得られる分析値の信頼性は低いという問題点がある。
すなわち、ＳＥＣを用いた高分子重合物の平均分子量の解析は、平均分子量が既知である複数の標準物質を測定した後に、それぞれの標準物質の溶出時間と平均分子量の対数をプロットすることによって得られる較正曲線を用いて、測定試料のクロマトグラムを較正することによって、初めて平均分量の決定が行われる。そのための標準物質は、測定試料と同一の分子構造をもつものであることが望ましいが、市販品として一般に入手が容易な標準物質は、ポリスチレン、ポリメタクリル酸メチル、ポリエチレングリコール、プルランなど数種に限られている。従って、通常のＳＥＣで求められる平均分子量とは、試料の分子量に基づく絶対平均分子量ではなく、標準物質を測定した条件で得られた較正曲線によって換算された相対平均分子量であるため、その値の信頼性は低い。
【０００４】
高分子重合物の平均分子量及び分子量分布を測定する別の方法として、マトリックス支援レーザー脱離イオン化法やエレクトロスプレーイオン化法などのソフトイオン化法を用いたＭＳ測定により、高分子重合物の構成成分を分子量ごとにマススペクトル上で分離して観測し、各成分のピーク質量数及びピーク強度の分布から、信頼性の高い絶対平均分子量及び絶対分子量分布を測定する方法が提案されている［非特許文献２］。しかしながら、ソフトイオン化ＭＳでは、高分子化合物は、イオン化効率や検出器の感度などに分子量依存性があるため、正確な測定値を求めることができる試料は、分子量分布が狭い高分子重合物に限定されることとなる（非特許文献３）。
【０００５】
そこで、標準物質が必要なＳＥＣと、分子量分布の狭い試料しか測定できないソフトイオン化ＭＳの短所を補完する方法として、ＳＥＣで狭い分子量分布をもつ画分を細かく分取し、それらをソフトイオン化ＭＳにより分析することによって各画分に存在する成分の平均分子量を求め、それらの値を用いてＳＥＣの較正曲線を作成することによって絶対平均分子量を測定する方法（以下、ＳＥＣ−ＭＳという）が提案されている（非特許文献４）。
このＳＥＣ−ＭＳを用いる方法は、標準物質を用いることなく絶対平均分子量及び絶対分子量分布を解析できる点で、一般に使用されるＳＥＣよりは優れているが、その解析結果が、信頼性の低いＳＥＣの分離能に依存していることは、大きな欠点である。さらに、このＳＥＣ−ＭＳを用いる方法では、高分子重合物を構成する成分の組成や、同族体列が複数含まれる高分子重合物については、同族体列ごとの平均分子量及び分子量分布、分子量に応じた組成を求めることはできないという問題点がある。
【０００６】
【特許文献１】特開平０６−３１７５７５
【特許文献２】特開平０６−２８８９９７
【特許文献３】特開平０６−１０９７１５
【特許文献４】特開平０５−１４２２１８
【特許文献５】特開平０５−１４２２１７
【特許文献６】特開平０５−０８７７９７
【特許文献７】特開平０９−２８１０９７
【非特許文献１】サイズ排除クロマトグラフィー、森定雄著、共立出版（１９９１）
【非特許文献２】Ｅｕｒ．ＭａｓｓＳｐｅｃｔｒｏｍ．，１，２９３（１９９５）
【非特許文献３】ＲａｐｉｄＣｏｍｍｕｎ．ＭａｓｓＳｐｅｃｔｒｏｍ．，９，４５３（１９９５）
【非特許文献４】ＭａｓｓＳｐｅｃｔｒｏｍ．Ｒｅｖ．，１６，２８３（１９９７）
【０００７】
【発明が解決しようとする課題】
本発明の課題は、ＳＥＣ−ＭＳを用いて高分子重合体の分子量及び分子量分布を測定する方法において、より実際の状態を表すと考えられる高分子重合体の絶対平均分子量分布及び絶対平均分子量の測定方法、絶対平均分子量の測定方法、複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法、及び高分子重合物を構成する成分の絶対組成を測定する方法、及びＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法を提供することである。
【０００８】
【課題を解決するための手段】
そこで、本発明者らは、測定値の信頼性がＳＥＣの分離能に依存するという従来技術のＳＥＣ−ＭＳの問題を克服するために検討を重ね、従来技術のＳＥＣ−ＭＳで行われてきたクロマトグラムの分子量較正操作を行わない、新しいＳＥＣ−ＭＳの解析方法を発明した。具体的には、ＳＥＣ装置の検出器が画分に含まれる成分の物質量の総和を正確に分析できるという長所に着目し、ＳＥＣにより分取された各画分をＭＳ測定して得られたマススペクトルのピーク強度を、対応する画分に対して観測されたＳＥＣの検出器信号強度に基づいて感度補正し、それらを合算することによって該高分子重合物を構成する成分ごとの分子量と物質量の関係を解析できることを見出した。
【０００９】
この解析によれば、分子量の計算結果は、ＳＥＣの分離能に依存することがないので、ＳＥＣの分離能に依存することがなく、絶対分子量分布、絶対平均分子量、及び組成が決定でき、さらに従来技術のＳＥＣおよびＳＥＣ−ＭＳでは特殊な場合を除き不可能であった、末端基化学構造等の微細化学構造が異なる複数の同族体列からなる高分子重合物や、複数の高分子重合物からなる高分子ブレンドなど、同族体列が複数含まれる高分子重合物についても、絶対分子量分布、絶対平均分子量、及び組成を決定することが可能となったものである。
【００１０】
本発明によれば、以下の発明が提供される。
（１）高分子重合物の絶対分子量分布を測定する方法において、サイズ排除クロマトグラフィー（以下、ＳＥＣとも言う）による分析方法、質量分析装置（以下、ＭＳとも言う）による分析方法及びこれらの分析方法によるデータ処理からなり、ＳＥＣによる分析方法により（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の工程による処理を行い、次に（Ｃ）の工程により分取された画分についてＭＳによる分析方法により（Ｅ）および（Ｆ）の工程による処理を行い、（Ｄ）、（Ｅ）、及び（Ｆ）の工程による測定結果から、データ処理により（Ｇ）の工程の処理を行い、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理により（Ｈ）の工程の操作を行い、これらの結果からデータ処理により（Ｉ）の工程の処理を行うことによりＭＳによる分析方法の測定結果をＳＥＣによる分析の測定方法の結果によって補正することを特徴とする高分子重合物の絶対分子量分布を測定する方法。
（Ａ）高分子重合物をＳＥＣで分離する工程
（Ｂ）工程（Ａ）により分離された高分子重合物を検出する工程
（Ｃ）工程（Ａ）により分離された高分子重合物を、工程（Ｂ）と同時あるいは直後に連続的に分取する工程
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程
（Ｅ）工程（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する工程
（Ｆ）工程（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する工程
（Ｇ）工程（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、工程（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する工程
（Ｈ）工程（Ｄ）から（Ｇ）までの操作を、工程（Ｃ）により分取された全画分について行う工程
（Ｉ）工程（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める工程
（２）前記工程（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する方式によることを特徴とする（１）記載の高分子重合物の分子量分布を測定する方法。
（３）前記検出が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（２）記載の高分子重合物の分子量分布を測定する方法。
（４）前記工程（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含することを特徴とする（１）記載の高分子重合物の分子量分布を測定する方法。
（５）前記工程（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化を用いて行われることを特徴とする（４）記載の高分子重合物の分子量分布を測定する方法。
（６）前記イオン化法が、マトリックス支援レーザー脱離イオン化法、エレクトロスプレーイオン化法、電界脱離イオン化法、プラズマディソープションイオン化法、または高速粒子衝撃イオン化法により行われることを特徴とする（５）記載の高分子重合物の分子量分布を測定する方法。
（７）前記工程（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析方式を用いて行われることを特徴とする（１）記載の高分子重合物の分子量分布を測定する方法。
【００１１】
（８）高分子重合物の絶対平均分子量を測定する方法において、
ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理からなり、ＳＥＣによる分析方法により（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の工程による処理を行い、次に（Ｃ）の工程により分取された画分についてＭＳによる分析方法により（Ｅ）および（Ｆ）の工程による処理を行い、（Ｄ）、（Ｅ）、及び（Ｆ）の工程による測定結果から、データ処理により（Ｇ）の処理を行い、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理により（Ｈ）の工程の操作を行い、これらの結果からデータ処理により（Ｉ）の工程の処理を行うことにより、ＭＳによる分析方法の測定結果をＳＥＣの測定結果によって補正することを特徴とする高分子重合物の絶対平均分子量の測定方法。
（Ａ）高分子重合物をＳＥＣで分離する工程
（Ｂ）工程（Ａ）により分離された高分子重合物を検出する工程
（Ｃ）工程（Ａ）により分離された高分子重合物を、工程（Ｂ）と同時あるいは直後に連続的に分取する工程
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程
（Ｅ）工程（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する工程
（Ｆ）工程（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する工程
（Ｇ）工程（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、工程（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する工程
（Ｈ）工程（Ｄ）から（Ｇ）までの操作を、工程（Ｃ）により分取された全画分について行う工程
（Ｉ）工程（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める工程
（９）前記工程（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する方式によることを特徴とする（８）記載の高分子重合物の絶対平均分子量の測定方法。
（１０）前記検出が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（９）記載の高分子重合物の絶対平均分子量の測定方法。
（１１）前記工程（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含することを特徴とする（８）記載の高分子重合物の絶対平均分子量の測定方法。
（１２）前記工程（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化を用いて行われることを特徴とする（８）記載の高分子重合物の絶対平均分子量の測定方法。
（１３）前記イオン化法が、マトリックス支援レーザー脱離イオン化法、エレクトロスプレーイオン化法、電界脱離イオン化法、プラズマディソープションイオン化法、または高速粒子衝撃イオン化法により行われることを特徴とする（１２）記載の高分子重合物の絶対平均分子量の測定方法。
（１４）前記工程（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析方式を用いて行われることを特徴とする（８）記載の高分子重合物の絶対平均分子量の測定方法。
【００１２】
（１５）高分子重合物を構成する成分の組成を測定する方法において、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理からなり、ＳＥＣによる分析により（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の工程による処理を行い、次に（Ｃ）の工程により分取された画分についてＭＳを用いる分析方法により（Ｅ）および（Ｆ）の工程による処理を行い、（Ｄ）、（Ｅ）及び（Ｆ）の工程による測定結果から、データ処理により（Ｇ）の工程の処理を行い、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理により（Ｈ）の工程の操作を行い、これらの結果からデータ処理により（Ｉ）の工程の処理を行うことによりＭＳによる分析方法の記測定結果をＳＥＣによる分析方法による測定結果によって分子量に依存した組成を補正することを特徴とする高分子重合物を構成する成分の組成を測定する方法。
（Ａ）高分子重合物をＳＥＣで分離する工程
（Ｂ）工程（Ａ）により分離された高分子重合物を検出する工程
（Ｃ）工程（Ａ）により分離された高分子重合物を、工程（Ｂ）と同時あるいは直後に連続的に分取する工程
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程
（Ｅ）工程（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する工程
（Ｆ）工程（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する工程
（Ｇ）工程（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、工程（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する工程
（Ｈ）工程（Ｄ）から（Ｇ）までの操作を、工程（Ｃ）により分取された全画分について行う工程
（Ｉ）工程（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める工程
（１６）前記工程（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出することを特徴とする（１５）記載の高分子重合物を構成する成分の組成を測定する方法。
（１７）前記検出することが、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（１６）記載の高分子重合物を構成する成分の組成を測定する方法。
（１８）前記工程（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含することを特徴とする請求項１５記載の高分子重合物を構成する成分の組成を測定する方法。
（１９）前記工程（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化により行われることを特徴とする（１５）記載の高分子重合物を構成する成分の組成を測定する方法。
（２０）前記イオン化が、マトリックス支援レーザー脱離イオン化、エレクトロスプレーイオン化、電界脱離イオン化、プラズマディソープションイオン化、または高速粒子衝撃イオン化により行われることを特徴とする（１９）記載の高分子重合物を構成する成分の組成を測定する方法。
（２１）前記工程（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析方法を用いて行われることを特徴とする（１５）記載の高分子重合物を構成する成分の組成を測定する方法。
【００１３】
（２２）複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの測定方法において、ＳＥＣによる分析方法、ＭＳによる分析方法及びこれらの分析方法によるデータ処理からなり、ＳＥＣにより分析方法により（Ａ）、（Ｂ）、（Ｃ）及び（Ｄ）の工程による処理を行い、次に（Ｃ）の工程により分取された画分についてＭＳによる分析方法により（Ｅ）および（Ｆ）の工程による処理を行い、（Ｄ）、（Ｅ）、及び（Ｆ）の工程による測定結果から、データ処理により（Ｇ）の工程の処理を行い、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理により（Ｈ）の工程の操作を行い、これらの測定結果からデータ処理により（Ｉ）の処理を行うことにより分子量に依存した組成を測定することを特徴とする複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの測定方法。
（Ａ）高分子重合物をＳＥＣで分離する工程
（Ｂ）工程（Ａ）により分離された高分子重合物を検出する工程
（Ｃ）工程（Ａ）により分離された高分子重合物を、工程（Ｂ）と同時あるいは直後に連続的に分取する工程
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程
（Ｅ）工程（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する工程
（Ｆ）工程（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する工程
（Ｇ）工程（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、工程（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する工程
（Ｈ）工程（Ｄ）から（Ｇ）までの操作を、工程（Ｃ）により分取された全画分について行う工程を行い、
（Ｉ）前記工程（Ｆ）において得られた高分子重合物を構成する各成分の分子量から高分子重合物に存在する同族体列を帰属し、解析される全画分に存在する同族体列ごとの数分率あるいは数分率に比例した値の総和を求めることを特徴とする複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法。
（２３）前記工程（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する方式によることを特徴とする（２２）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法。
（２４）前記検出が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（２３）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法。
（２５）前記工程（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含することを特徴とする（２２）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法。
（２６）前記工程（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化を用いて行われることを特徴とする（２２）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法。
（２７）前記イオン化法が、マトリックス支援レーザー脱離イオン化法、エレクトロスプレーイオン化法、電界脱離イオン化法、プラズマディソープションイオン化法、または高速粒子衝撃イオン化法により行われることを特徴とする（２６）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法。
（２８）前記工程（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析方式を用いて行われることを特徴とする（２２）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析方法。
【００１４】
（２９）高分子重合物を構成する成分ごとの溶出挙動を測定する方法において、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理からなり、ＳＥＣによる分析法により（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の処理を行い、次に（Ｃ）の操作により分取された画分についてＭＳを用いる分析方法により（Ｅ）および（Ｆ）の処理を行い、（Ｄ）、（Ｅ）、及び（Ｆ）から得られる結果から、データ処理により（Ｇ）の処理を行い、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理により（Ｈ）の処理を行い、これらの結果からデータ処理により（Ｉ）の処理を行うことを特徴とする高分子重合物を構成する成分ごとの溶出挙動を測定することを方法。
（Ａ）高分子重合物をＳＥＣで分離する工程
（Ｂ）工程（Ａ）により分離された高分子重合物を検出する工程
（Ｃ）工程（Ａ）により分離された高分子重合物を、工程（Ｂ）と同時あるいは直後に連続的に分取する工程
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程を行い、
（Ｅ）工程（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する工程
（Ｆ）工程（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する工程
（Ｇ）工程（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、工程（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する工程
（Ｈ）工程（Ｄ）から（Ｇ）までの操作を、工程（Ｃ）により分取された全画分について行う工程を行い、高分子重合物を構成する各成分の数分率あるいは数分率に比例した値を、画分を分取した時間に対して求めることを特徴とするＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
（３０）前記工程（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する方式によることを特徴とする（２９）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
（３１）前記検出が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（３０）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
（３２）前記工程（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含することを特徴とする（２９）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
（３３）前記工程（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化を用いて行われることを特徴とする（２９）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
（３４）前記イオン化法が、マトリックス支援レーザー脱離イオン化法、エレクトロスプレーイオン化法、電界脱離イオン化法、プラズマディソープションイオン化法、または高速粒子衝撃イオン化法により行われることを特徴とする（３３）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
【００１５】
（３６）高分子重合物の絶対分子量分布を測定する装置において、ＳＥＣ、ＭＳ及びデータ処理装置から構成され、ＳＥＣにより（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の処理を行う装置、次に（Ｃ）の工程により分取された画分についてＭＳを用いて（Ｅ）および（Ｆ）の処理を行う装置、前記（Ｄ）、（Ｅ）、及び（Ｆ）の装置から得られる結果から、データ処理装置により（Ｇ）の処理を行う装置、ＳＥＣ、ＭＳ及びデータ処理装置からなる（Ｈ）の処理を行う装置、及びこれらの結果からデータ処理装置の（Ｉ）の処理装置により、ＭＳの測定結果をＳＥＣの測定結果によって補正する装置から構成されることを特徴とする高分子重合物の絶対分子量分布を測定装置。
（Ａ）高分子重合物をＳＥＣで分離する装置
（Ｂ）装置（Ａ）により分離された高分子重合物を検出する装置
（Ｃ）装置（Ａ）により分離された高分子重合物を、装置（Ｂ）と同時あるいは直後に連続的に分取する装置
（Ｄ）装置（Ｃ）により分取された画分の数分率あるいは重量分率を、装置（Ｂ）により検出された信号強度から解析する装置
（Ｅ）装置（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する装置
（Ｆ）装置（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する装置
（Ｇ）装置（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、装置（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する装置
（Ｈ）装置（Ｄ）から（Ｇ）までの操作を、工程（Ｃ）により分取された全画分について行う装置
（Ｉ）装置（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める装置。
（３７）前記装置（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する装置によることを特徴とする（３６）記載の
高分子重合物の絶対分子量分布を測定装置。
（３８）前記検出する装置が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（３７）記載の高分子重合物の絶対分子量分布を測定する装置。
（３９）前記装置（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含する装置が設けられていることを特徴とする（３６）記載の高分子重合物の絶対分子量分布の測定装置。
（４０）前記装置（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化を用いて行われる装置であることを特徴とする（３９）記載の高分子重合物の絶対分子量分布を測定装置。
（４１）前記イオン化を用いて行われる装置が、マトリックス支援レーザー脱離イオン装置、エレクトロスプレーイオン化装置、電界脱離イオン化装置、プラズマディソープションイオン化装置、または高速粒子衝撃イオン化装置により行われることを特徴とする（４０）記載の高分子重合物の絶対分子量分布の測定装置。
（４２）前記装置（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析装置を用いて行われることを特徴とする請求項３６記載の高分子重合物の絶対分子量分布の測定装置。
【００１６】
（４３）高分子重合物の絶対平均分子量を測定する装置において、ＳＥＣ、ＭＳ及びデータ処理装置から構成され、ＳＥＣにより（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の処理を行う装置、次に（Ｃ）の装置により分取された画分についてＭＳを用いて（Ｅ）および（Ｆ）の処理を行う装置、前記（Ｄ）、（Ｅ）、及び（Ｆ）の装置から得られる結果から、データ処理装置により（Ｇ）の処理を行う装置、
ＳＥＣ、ＭＳ及びデータ処理装置を用いて（Ｈ）の操作を行い、これらの結果らデータ処理装置による（Ｉ）の処理装置により、ＭＳの測定結果をＳＥＣの測定結果によって補正する装置から構成されることを特徴とする高分子重合物の絶対平均分子量の測定装置。
（Ａ）高分子重合物をＳＥＣで分離する装置
（Ｂ）装置（Ａ）により分離された高分子重合物を検出する装置
（Ｃ）装置（Ａ）により分離された高分子重合物を、装置（Ｂ）と同時あるいは直後に連続的に分取する装置
（Ｄ）装置（Ｃ）により分取された画分の数分率あるいは重量分率を、装置（Ｂ）により検出された信号強度から解析する装置
（Ｅ）装置（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する装置
（Ｆ）装置（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する装置
（Ｇ）装置（Ｅ）により測定された信号強度を、装置（Ｄ）による解析に基づき補正することによって、装置（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する装置
（Ｈ）装置（Ｄ）から（Ｇ）までの操作を、装置（Ｃ）により分取された全画分について行う工程
（Ｉ）装置（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める装置
（４４）前記装置（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する装置によることを特徴とする（４３）記載の高分子重合物の絶対平均分子量の測定装置。
（４５）前記検出する装置が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（４４）記載の高分子重合物の絶対平均分子量の測定装置。
（４６）前記装置（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含する装置が設けられていることを特徴とする（４３）記載の高分子重合物の絶対平均分子量の測定装置。
（４７）前記装置（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化装置を用いて行われることを特徴とする（４３）記載の高分子重合物の絶対平均分子量の測定装置。
（４８）前記イオン化装置が、マトリックス支援レーザー脱離イオン化装置、エレクトロスプレーイオン化装置、電界脱離イオン化装置、プラズマディソープションイオン化装置、または高速粒子衝撃イオン化装置により行われることを特徴とする（４７）記載の高分子重合物の絶対平均分子量の測定装置。
（４９）前記装置（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析装置を用いて行われることを特徴とする（４８）記載の高分子重合物の絶対平均分子量の測定装置。
【００１７】
（５０）高分子重合物を構成する成分の組成を測定する装置において、ＳＥＣ、ＭＳ及びデータ処理装置から構成され、ＳＥＣにより（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の処理を行う装置、次に（Ｃ）の装置により分取された画分についてＭＳを用いて（Ｅ）および（Ｆ）の処理を行う装置、（Ｄ）、（Ｅ）、及び（Ｆ）の測定装置から得られる結果から、データ処理装置により（Ｇ）の処理を行う装置、ＳＥＣ、ＭＳ及びデータ処理装置を用いて（Ｈ）の操作を行い、これらの結果からデータ処理装置により（Ｉ）の処理を行うことにより、ＭＳの測定結果をＳＥＣの測定結果によって分子量に依存した組成を補正する装置から構成されることを特徴とする高分子重合物を構成する成分の組成を測定装置。
（Ａ）高分子重合物をＳＥＣで分離する装置
（Ｂ）装置（Ａ）により分離された高分子重合物を検出する装置
（Ｃ）装置（Ａ）により分離された高分子重合物を、装置（Ｂ）と同時あるいは直後に連続的に分取する装置
（Ｄ）装置（Ｃ）により分取された画分の数分率あるいは重量分率を、装置（Ｂ）により検出された信号強度から解析する装置
（Ｅ）装置（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する装置
（Ｆ）装置（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する装置
（Ｇ）装置（Ｅ）により測定された信号強度を、装置（Ｄ）による解析に基づき補正することによって、装置（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する装置
（Ｈ）装置（Ｄ）から（Ｇ）による操作を、装置（Ｃ）により分取された全画分について行う装置
（Ｉ）装置（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める装置
（５１）前記装置（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する装置によることを特徴とする（５０）記載の高分子重合物を構成する成分の組成を測定装置。
（５２）前記検出する装置が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（５１）記載の高分子重合物を構成する成分の組成を測定する装置。
（５３）前記装置（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含する装置が設けられていることを特徴とする（５０）記載の高分子重合物を構成する成分の組成を測定する装置。
（５４）前記装置（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化装置を用いて行われることを特徴とする（５０）記載の高分子重合物を構成する成分の組成を測定装置。
（５５）前記イオン化装置が、マトリックス支援レーザー脱離イオン化装置、エレクトロスプレーイオン化装置、電界脱離イオン化装置、プラズマディソープションイオン化装置、または高速粒子衝撃イオン化装置により行われることを特徴とする（５４）記載の高分子重合物を構成する成分の組成を測定装置。
（５６）前記装置（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析装置を用いて行われることを特徴とする（５０）記載の高分子重合物を構成する成分の組成を測定装置。
【００１８】
（５７）複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの測定装置において、サイズ排除クロマトグラフィー（以下、ＳＥＣ）、質量分析装置（以下、ＭＳ）及びデータ処理装置から構成され、ＳＥＣにより分析装置により（Ａ）、（Ｂ）、（Ｃ）及び（Ｄ）の装置による処理を行い、次に（Ｃ）の装置により分取された画分についてＭＳによる分析装置により（Ｅ）および（Ｆ）の装置による処理を行い、（Ｄ）、（Ｅ）、及び（Ｆ）の装置による測定結果から、データ処理装置の（Ｇ）の装置による処理を行い、ＳＥＣ、ＭＳ及びデータ処理装置による（Ｈ）の装置による処理操作を行い、これらの測定結果からデータ処理装置により（Ｉ）の装置による処理を行うことにより分子量に依存した組成を補正することを特徴とする複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの測定装置。
（Ａ）高分子重合物をＳＥＣで分離する装置
（Ｂ）装置（Ａ）により分離された高分子重合物を検出する装置
（Ｃ）装置（Ａ）により分離された高分子重合物を、装置（Ｂ）と同時あるいは直後に連続的に分取する装置
（Ｄ）装置（Ｃ）により分取された画分の数分率あるいは重量分率を、装置（Ｂ）により検出された信号強度から解析する装置
（Ｅ）装置（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析装置によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する装置
（Ｆ）装置（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する装置
（Ｇ）装置（Ｅ）により測定された信号強度を、装置（Ｄ）による解析に基づき補正することによって、装置（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する装置
（Ｈ）装置（Ｄ）から（Ｇ）までの処理による操作を、装置（Ｃ）により分取された全画分について行う装置による処理を行い、
（Ｉ）前記装置（Ｆ）において得られた高分子重合物を構成する各成分の分子量から高分子重合物に存在する同族体列を帰属し、解析される全画分に存在する同族体列ごとの数分率あるいは数分率に比例した値の総和を求める装置から構成されることを特徴とする複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つを測定する高分子重合物の分析装置。
（５８）前記装置（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する装置によることを特徴とする（５７）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つを測定する高分子重合物の分析装置。
（５９）前記検出する装置が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（５８）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つを測定する高分子重合物の分析装置。
（６０）前記装置（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すステップを包含する装置を設けることを特徴とする（５７）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つを測定する高分子重合物の分析装置。
（６１）前記装置（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化装置を用いて行われることを特徴とする（５７）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つを測定する高分子重合物の分析装置。
（６２）前記イオン化装置が、マトリックス支援レーザー脱離イオン化装置、エレクトロスプレーイオン化装置、電界脱離イオン化装置、プラズマディソープションイオン化装置、または高速粒子衝撃イオン化装置により行われることを特徴とする（６１）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの方法を測定する高分子重合物の分析装置。
（６３）前記装置（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析装置を用いて行われることを特徴とする（５７）記載の複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの装置によりを測定する高分子重合物の分析装置。
【００１９】
（６４）高分子重合物を構成する成分ごとの溶出挙動を測定する装置において、ＳＥＣ、ＭＳ及びデータ処理装置から構成され、ＳＥＣにより（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の処理を行う装置、次に（Ｃ）の装置により分取された画分についてＭＳを用いて（Ｅ）および（Ｆ）の処理を行う装置、（Ｄ）、（Ｅ）、及び（Ｆ）の測定装置から得られる結果から、データ処理装置により（Ｇ）の処理を行う装置、（Ｈ）及び（Ｉ）の処理装置により分子量に依存した組成を測定する装置から構成されることを特徴とする高分子重合物を構成する成分の組成を測定する装置。
（Ａ）高分子重合物をＳＥＣで分離する装置
（Ｂ）装置（Ａ）により分離された高分子重合物を検出する装置
（Ｃ）装置（Ａ）により分離された高分子重合物を、装置（Ｂ）と同時あるいは直後に連続的に分取する装置
（Ｄ）装置（Ｃ）により分取された画分の数分率あるいは重量分率を、装置（Ｂ）により検出された信号強度から解析する工程を行い、
（Ｅ）装置（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する装置
（Ｆ）装置（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する装置
（Ｇ）装置（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、装置（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する装置
（Ｈ）工程（Ｄ）から（Ｇ）までの操作を、工程（Ｃ）により分取された全画分について行う装置により、高分子重合物を構成する各成分の数分率あるいは数分率に比例した値を、画分を分取した時間に対して求める装置から構成されることを特徴とするＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
（６５）前記工程（Ｂ）が、数分率または重量分率に基づいた物質量に比例した信号を検出する方式によることを特徴とする（６４）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する方法。
（６６）前記検出する装置が、示差屈折検出器あるいは紫外可視検出器により行われることを特徴とする（６５）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する装置。
（６７）前記装置（Ｅ）で質量／電荷比を測定する前に、さらに前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施す装置が設けられていることを特徴とする（６４）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する装置。
（６８）前記装置（Ｅ）が、画分に含まれる成分の分子量分布を反映した分子量関連イオンを生成するイオン化を用いて行われることを特徴とする（６４）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する装置。
（６９）前記イオン化装置が、マトリックス支援レーザー脱離イオン化装置、エレクトロスプレーイオン化装置、電界脱離イオン化装置、プラズマディソープションイオン化装置、または高速粒子衝撃イオン化装置により行われることを特徴とする（６８）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する装置。
（７０）前記装置（Ｅ）が、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、及びこれらの複合型よりなるグループより選択される質量分析装置を用いて行われることを特徴とする（６４）記載のＳＥＣ測定における高分子重合物を構成する成分ごとの溶出挙動を測定する装置。
【００２０】
【発明の実施の形態】
本発明の方法を実施する装置構成の一例を図面に基づいて説明する。
図１は、本発明を実施する装置の一例である。
ＳＥＣ装置（Ａ）は、移動相貯留槽１、送液ポンプ２、オートサンプラー３、カラムオーブン４、分離カラム５、ＲＩ検出器６、及び排出口７から構成されている。ＭＳ装置（Ｂ）は、ＭＡＬＤＩ−ＴＯＦＭＳを用い、試料プレート９、試料室１０、紫外レーザー１１、引き出し電極１２、フライトチューブ１３、及びマルチチャンネル検出器１４から構成されている。
前記ＳＥＣ装置（Ａ）及びＭＳ装置（Ｂ）から得られるデータの処理装置（Ｃ）は、前記各装置に接続されており、ＭＳ用データ処理装置１５及びＳＥＣ用データ処理装置８並びにＳＥＣとＭＳのデータを受けて、両者を併せてデータ処理するためのデータ処理装置１６から構成されている。
なお、この図では、ＳＥＣ装置とＭＳ装置は、物理的に分離しているが、実際に装置を組み立てる場合には、排出口７から得られる分離された高分子重合物（分取された画分に存在する高分子重合物）を、ＭＳ装置の試料プレート９に供給することの手段により接続することができる。その接続部分には、ＭＳ装置により質量／電荷比を測定する前に、前処理として乾燥、濃縮、希釈、脱塩、誘導体化、ないしはイオン化に必要な試薬の添加を施すための手段を設置することができる。
【００２１】
ＳＥＣ測定および分取に際しては、移動相貯留槽１からポンプ２によりあらかじめ移動相を流し、定常状態を作る。次に、オートサンプラー３から試料を注入する。注入された試料は、移動相によりカラムオーブン４中の分離カラム５に導入されて分子量分離された後、ＲＩ検出器６で検出され、排出口７から排出される。この分子量に応じて分離された試料成分を含む移動相を、排出口７で一定時間ごとに連続して分取し、各画分をＭＳ測定に供する。なお、ＲＩ検出器６で得られたデータは、ＳＥＣ用データ処理装置８で処理し、クロマトグラムを描き、各画分の重量分率を計算することができる。
【００２２】
ＳＥＣの工程は、以下の工程から構成され、又、本発明の装置は以下の装置から構成される。
（Ａ）高分子重合物をＳＥＣで分離する工程及び装置
（Ｂ）工程（Ａ）により分離された高分子重合物を検出する工程及び装置
（Ｃ）工程（Ａ）により分離された高分子重合物を、工程（Ｂ）と同時あるいは直後に連続的に分取する工程及び装置
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程及び装置
【００２３】
ＳＥＣ装置および分離カラム（前記工程（Ａ）から（Ｃ））については、分子量分布を反映したマススペクトルが観測できる画分が分取できるものであればよい。例えば、ＭＳ装置にＭＡＬＤＩ−ＴＯＦＭＳを用いる場合では、測定する画分の分子量分布は、多分散度（重量平均分子量と数平均分子量の比）が１．１以下であることが好ましい（前出非特許文献３）とされるが、このような画分は、一般に分析用のＳＥＣ測定で行われている典型的な分離条件で１０〜１０００μｌ程度を分取することによって、比較的容易に得ることができる。ここでいう典型的な分離条件とは、分離カラムの充填剤として、通常のゲルパーミエーションクロマトグラフィー（有機溶媒を用いたＳＥＣ）に用いられている多孔性スチレン−ジビニルベンゼン系共重合体粒子や、ゲルフィルトレーションクロマトグラフィー（水系溶媒を用いたＳＥＣ）に用いられる多孔性メタクリル酸エステル系共重合体や多孔性ビニルアルコール系共重合体粒子などを用い、その平均粒子径は３〜３０μｍの範囲にあり、充填剤を充填した分離カラムの内径は４．６〜７．８ｍｍで長さが７．５〜３０ｃｍの範囲にあり、測定条件としては、試料濃度が０．１〜１．０ｍｇ／ｍｌで流速０．３５〜１．０ｍｌ／分の移動相溶媒中に試料溶液を１０〜２００μｌの範囲で注入した場合である。もちろん、これは典型例であって、本発明はこのＳＥＣ分離の条件に制限されるものではない。さらに加えるならば、通常のＳＥＣ測定では不適当と判断される、流路内での拡散現象や試料とカラム充填剤との相互作用などがある程度起こる分離条件であってさえも、本発明では、分子量分布を反映したマススペクトルが観測される画分が分取できる分離条件を満たすのであれば許容されるため、本発明におけるＳＥＣの分離条件はむしろ一般のＳＥＣおよびＳＥＣ−ＭＳの場合よりも寛容である。
【００２４】
ＳＥＣ装置の検出器（前記工程（Ｄ））は、各画分の物質量に比例した応答値を得ることができるものであればよい。例えば、ＲＩ検出器は試料の化学構造によらず単位時間当たりに検出器を通過する成分の重量分率に比例した応答を示すため、好ましい検出器として挙げられる。また、ＵＶ検出器は、単位時間当たりに検出器を通過する成分の重量分率あるいは数分率に比例した応答が得られる試料を測定する場合にあっては、好ましい検出器として挙げられる。もちろん、所期の目的を達成できるものであれば、ＳＥＣ検出器の種類は上記に限定されない。
【００２５】
ＭＳ測定に際しては、ＭＳ測定の前処理として、各画分の試料溶液をマトリックス剤及びカチオン化剤と混合し、試料プレート９に滴下して乾燥させる。次に、試料プレート９を高真空に保たれた試料室１０へ導入し、試料、マトリックス剤、及びカチオン化剤の混合結晶の表面へ、紫外レーザー１１から発振された紫外レーザー光線を照射し、試料分子をイオン化する。イオンは、試料プレート９と引き出し電極１２の間の電位差によって加速され、フライトチューブ１３を飛行する過程で質量分離され、マルチチャンネルプレート検出器１４で検出される。このデータを、ＭＳ用データ処理装置１５で処理し、マススペクトルを得る。
【００２６】
ＭＳ装置については、分取された各画分の分子量分布を反映した分子量関連ピークから構成されるマススペクトルが得られるものであればよく、そのためのソフトイオン化法としてマトリックス支援レーザー脱離イオン化方法及び装置、エレクトロスプレーイオン化方法及び装置、電解脱離イオン化方法及び装置、プラズマディソープションイオン化方法及び装置、高速粒子衝撃法などが挙げられ、また、分子量関連イオンをその質量／電荷比の違いにより質量分離する方法及び装置として、飛行時間型、四重極型、イオントラップ型、セクター型、フーリエ変換型、あるいはそれらを組み合わせた複合型などが挙げられるが、所期の目的を達成できるものであれば、イオン化法及び装置、並びに質量分離部の種類は上記に限定されず、またそれらの組み合わせは任意である。このうち、現在好ましいのは、マトリックス支援レーザー脱離イオン化法及び装置と飛行時間型の質量分離部を組み合わせたＭＡＬＤＩ−ＴＯＦＭＳや、エレクトロスプレーイオン化法及び装置と四重極型あるいは飛行時間型の質量分離部を組み合わせたＥＳＩ−ＭＳである。
【００２７】
ＭＳの工程は、以下の工程から構成され、又、本発明の装置は以下の装置から構成される。
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程
（Ｅ）工程（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、質量分析によって質量／電荷比に基づいて分離し、それぞれの信号強度を測定する工程
（Ｆ）工程（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する工程
【００２８】
ＳＥＣ装置（Ａ）及びＭＳ装置（Ｂ）から得られるデータの処理装置（Ｃ）は、ＭＳ用データ処理装置１５及びＳＥＣ用データ処理装置８並びにＳＥＣとＭＳのデータを受けて、両者を併せてデータ処理するためのデータ処理装置１６から構成されている。具体的には、前記（Ｄ）、（Ｅ）、及び（Ｆ）の工程又は装置から得られる結果から、データ処理装置により以下の（Ｇ）の処理を行う工程又は装置である。
（Ｇ）工程又は装置（Ｅ）により測定された信号強度を、工程又は装置（Ｄ）による解析に基づき補正することによって、工程又は装置（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する工程又は装置
そして、ＳＥＣ、ＭＳ及びデータ処理装置を用いて「（Ｈ）工程又は装置による（Ｄ）から工程又は装置による（Ｇ）までの操作を、工程又は装置（Ｃ）により分取された全画分について行う工程又は装置」により行う。
次に、これらの結果からデータ処理装置により（Ｉ）の処理を行うことによりＭＳの測定結果をＳＥＣの測定結果によって補正する。「（Ｉ）工程又は装置（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める工程又は装置」。
【００２９】
本発明の方法の高分子重合物の絶対分子量分布及び絶対平均分子量を解析する方法を説明する。
ＳＥＣを用いて
（Ａ）高分子重合物をＳＥＣで分離する工程。
具体的には、高分子重合物の試料溶液をＳＥＣ装置に注入し、分離カラムで分離する。
次に、（Ｂ）前記（Ａ）により分離された高分子重合物を検出する工程。
具体的には、検出器により分離された成分の物質量に比例した信号を検出してＳＥＣクロマトグラムを測定する。
（Ｃ）工程（Ａ）により分離された高分子重合物を、工程（Ｂ）と同時あるいは直後に連続的に分取する工程
具体的には、検出器を通過した成分を連続的に分取する。あるいは、分離カラムの後で流路を分割し、一方の流路で分離された成分を検出し、もう一方で分取しても良い。いずれの場合でも、分離された成分の検出と分取の時間差が短いことが望ましい。
（Ｄ）工程（Ｃ）により分取された画分の数分率あるいは重量分率を、工程（Ｂ）により検出された信号強度から解析する工程
（Ｅ）工程（Ｃ）により分取された画分に存在する高分子重合物を構成する各成分を、ＭＳを用いて質量／電荷比に基づいて分離し、それぞれの信号強度を測定する工程
【００３０】
得られたＳＥＣクロマトグラム及びマススペクトルから絶対分子量分布及び絶対平均分子量を解析する方法は、ＳＥＣ装置の検出器の特性によって解析方法が若干異なるため、それぞれの場合に分けて説明する
［解析方法１］ＳＥＣ検出器が数分率による物質量に比例した応答を示す場合
これは、検出器を通過した成分の分子数に比例した信号を検出する場合に相当し、例えば高分子重合物の末端に特異的に存在する官能基を選択的にＵＶ検出器で検出する場合が挙げられる。
ある画分ｆに存在する成分の物質量の数分率Ｎ_ｆは、その画分に存在する成分ｉの分子数の数分率ｎ_ｆｉの和である。

一方、数分率ｎ_ｆｉは、画分ｆについて観測されたマススペクトル上の成分ｉのピーク強度Ｉ_ｆｉに比例するので、式（２）で表される。

式（１）及び式（２）から、比例係数ｋ_ｆを求める式（３）が導かれる。

Ｎ_ｆはＳＥＣクロマトグラム上の全ピーク面積に対する画分ｆに対応する部分の面積比として求められ（前記工程（Ｄ））、Ｉ_ｆｉはＭＳ測定（前記工程（Ｅ））の解析（工程（Ｆ）工程（Ｅ）により測定された質量／電荷比から高分子重合物を構成する各成分の分子量を決定する工程））により求められるので、結局、ｋ_ｆは計算により求めることができる（工程（Ｇ）工程（Ｅ）により測定された信号強度を、工程（Ｄ）による解析に基づき補正することによって、工程（Ｆ）で分子量が決定された各成分の数分率あるいは数分率に比例した値を解析する工程）
このｋ_ｆを、全ての画分について求める（前記工程（Ｈ））。
成分ｉは複数の画分に存在しているので、成分ｉの数分率の総和をｍ_ｉとすると、式（４）で表される（工程（Ｉ）工程（Ｈ）の操作を行うことによって解析される全画分に存在する各成分ごとに、数分率あるいは数分率に比例する値の総和を求める工程。）。

こうして求められるｍ_ｉは、成分ｉの組成（ｍｏｌ％）である。
成分ｉの分子量Ｍ_ｉは、前記工程（Ｆ）において成分ｉに対して測定された質量／電荷比およびＭＳ測定の測定条件等から決定されるので、ｍ_ｉをＭ_ｉに対してプロットすれば、絶対分子量分布を図示することができる。
さらに、ｍ_ｉとＭ_ｉから、高分子重合物の数平均分子量（Ｍ_ｎ）及び重量平均分子量（Ｍ_ｗ）を、それぞれ式（５）および式（６）により計算することができる。

また、分子量分布を表す指標である多分散度は、Ｍ_ｗとＭ_ｎの比で求められる。
【００３１】
［解析方法２］ＳＥＣ検出器が重量分率による物質量に比例した応答を示す場合
これは、ＳＥＣ測定に際して、例えば、ＲＩ検出器を用いる場合や、高分子重合物のモノマー単位が特異的に吸収する波長に設定したＵＶ検出器を用いる場合が挙げられる。
ある画分ｆに存在する成分の物質量の重量分率Ｗ_ｆは、その画分に存在する成分ｉの数分率ｎ_ｆｉと分子量Ｍ_ｆｉの積の和に比例する。

ここで、ａは比例係数である。
一方、数分率ｎ_ｆｉは、画分ｆについて観測されたマススペクトル上の成分ｉのピーク強度Ｉ_ｆｉに比例するので、式（８）で表される。

式（７）及び式（８）から、式（９）が導かれる。

Ｗ_ｆはＳＥＣクロマトグラム上の全ピーク面積に対する画分ｆに対応する部分の面積比として求められ（前記工程（Ｄ））、Ｉ_ｆｉ及びＭ_ｆｉはＭＳ測定（前記工程（Ｅ））の解析（前記工程（Ｆ））により求められるので、ｋ’_ｆは計算により求めることができる（前記工程（Ｇ））。このｋ’_ｆを、全ての画分について求める（前記工程（Ｈ））。
成分ｉは複数の画分に存在しているので、その数分率の総和をｍ_ｉとすると、式（１０）で表される（前記工程（Ｉ））。

しかし、比例係数ａが未知である場合は式（１０）によりｍ_ｉを求めることはできないので、一旦、式（１１）により数分率の総和に比例した値ｍ’_ｉを求める。

そして、式（１２）によりｍ’_ｉの百分率を計算すればａは消去され、成分ｉの組成ｍ_ｉがｍｏｌ％として求められる。

このようにして求めたｍ_ｉをＭ_ｉに対してプロットすれば、絶対分子量分布を図示することができる。
平均分子量の解析については、これ以降、Ｍ_ｎは式（５）を、Ｍ_ｗは式（６）を用いて求める。なお、比例係数ａは、Ｍ_ｎ及びＭ_ｗの計算過程で消去されるので、式（５）及び式（６）でｍ_ｉの代わりにｍ’_ｉを用いても良い。
以上の様に、本発明では、使用するＳＥＣ検出器の特性によって解析方法１あるいは２いずれかの方法により、ＳＥＣクロマトグラムとマススペクトルから、標準物質を用いずに絶対分子量分布、絶対平均分子量、及び組成を求めることができる
【００３２】
高分子重合物を構成する成分の組成を測定する方法では、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理からなり、ＳＥＣによる分析により（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の工程による処理を行い、次に（Ｃ）の工程により分取された画分についてＭＳを用いる分析方法により（Ｅ）および（Ｆ）の工程による処理を行い、（Ｄ）、（Ｅ）及び（Ｆ）の工程による測定結果から、データ処理により（Ｇ）の工程の処理を行い、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理により（Ｈ）の工程の操作を行い、これらの結果からデータ処理により（Ｉ）の工程の処理を行うことによりＭＳによる分析方法の記測定結果をＳＥＣによる分析方法による測定結果によって分子量に依存した組成を補正することにより高分子重合物を構成する成分の組成を測定する。
【００３３】
複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの測定方法では、以下、ＳＥＣによる分析方法、以下、ＭＳによる分析方法及びこれらの分析方法によるデータ処理からなり、ＳＥＣにより分析方法により（Ａ）、（Ｂ）、（Ｃ）及び（Ｄ）の工程による処理を行い、次に（Ｃ）の工程により分取された画分についてＭＳによる分析方法により（Ｅ）および（Ｆ）の工程による処理を行い、（Ｄ）、（Ｅ）、及び（Ｆ）の工程による測定結果から、データ処理により（Ｇ）の工程の処理を行い、ＳＥＣによる分析方法、ＭＳによる分析方法及びデータ処理により（Ｈ）の工程の操作を行い、これらの測定結果からデータ処理により（Ｉ）の処理を行うことにより分子量に依存した組成を測定することにより複数の同族体列からなる混合物である高分子重合物に含まれる同族体列ごとの絶対分子量分布、絶対平均分子量、及び高分子重合物を構成する成分の組成の中の少なくとも１つの測定を行う。
【００３４】
高分子重合物を構成する成分ごとの溶出挙動を測定する方法では、ＳＥＣ、ＭＳ及びデータ処理により、ＳＥＣにより（Ａ）、（Ｂ）、（Ｃ）、及び（Ｄ）の処理を行い、次に（Ｃ）の操作により分取された画分についてＭＳを用いて（Ｅ）および（Ｆ）の処理を行い、（Ｄ）、（Ｅ）、及び（Ｆ）の測定装置から得られる結果から、データ処理装置により（Ｇ）の処理を行い、ＳＥＣ、ＭＳ及びデータ処理装置を用いて（Ｈ）及びこれらの結果からデータ処理装置により（Ｉ）の処理を行うことにより、高分子重合物を構成する成分ごとの溶出挙動を測定する。
【００３５】
【実施例】
以下に、上記装置を用いて行った本発明について代表的な実施例を示し、さらに具体的に説明する。なお、これらは説明のための単なる例示であって、本発明はこれらになんら制限されるものではない。
実施例１
分子量が異なる２種類のＳＥＣ用標準ポリスチレン（市販品、東ソー（株）製）を混合した試料の絶対平均分子量、絶対分子量分布、及び組成について、以下の条件で分析を行った。
（１）試料調製
ポリスチレン▲１▼：Ｍ_ｎ＝９．３０×１０^３、Ｍ_ｗ＝９．４９×１０^３、Ｍ_ｗ／Ｍ_ｎ＝１．０２（以上、標準ポリスチレンを分子量較正に用いたＳＥＣ測定による）、Ｍ_ｗ＝１．０２×１０^４（光散乱法による）
ポリスチレン▲２▼：Ｍ_ｎ＝１．７０×１０^４、Ｍ_ｗ＝１．７１×１０^４、Ｍ_ｗ／Ｍ_ｎ＝１．０１（以上、標準ポリスチレンを分子量較正に用いたＳＥＣ測定による）、Ｍ_ｗ＝１．８１×１０^４（光散乱法による）
なお、上記の平均分子量は製造者（東ソー（株））より提供された参照値である。
ポリスチレン▲１▼１ｍｇ及び▲２▼１ｍｇを混合し、２ｍｌのクロロホルムに溶解して、試料溶液とした。
（２）分析条件
（２）−１ＳＥＣ測定及び分取
測定装置：ＨＬＣ−８２２０ＧＰＣ（東ソー（株）製）
分離カラム：ＴＳＫｇｅｌＧ−５０００Ｈｘｌ＋３０００Ｈｘｌ＋２０００Ｈｘｌ（東ソー（株）製）内径：７．８ｍｍ，長さ：１本あたり３０ｃｍ
カラム温度：４０℃
移動相：クロロホルム（流速：１ｍｌ／ｍｉｎ）
検出器：ＲＩ検出器（測定装置内蔵）
試料の注入量：１００μｌ
分取間隔：５秒（約８３μｌ）
【００３６】
（２）−２ＭＡＬＤＩ−ＴＯＦＭＳ測定
分取された各画分の溶出液を乾燥し、１０μｌのクロロホルムで再溶解した。その１μｌと、マトリックス溶液（１０ｍｇのジスラノールをクロロホルム１ｍｌに溶解した溶液）４μｌ、及びカチオン化剤溶液（１ｍｇのトリフルオロ酢酸を１ｍｌのアセトンに溶解した溶液）１μｌを混合し、その混合溶液１μｌを試料プレートに塗布、乾燥して結晶化させた。その試料プレートをＶｏｙａｇｅｒＤＥ−ＰＲＯＭＡＬＤＩ−ＴＯＦＭＳ（アプライドバイオシステムズジャパン（株）製）のイオン化室内に設置し、マススペクトルを得た。上記のＭＡＬＤＩ−ＴＯＦＭＳ測定を、ＳＥＣ測定におけるＲＩ検出器で応答が得られた全ての画分について行った。
【００３７】
（３）測定及び解析過程
上記ポリスチレン混合試料を分析した工程を、以下具体的に説明する。
前記工程（Ａ）として、ポリスチレン混合試料を図１中ＳＥＣ装置のオートサンプラー３から移動相に注入し、分離カラム５で分離した。
前記工程（Ｂ）として、分離された試料をＲＩ検出器６で検出し、図２に示すクロマトグラムを得た。
前記工程（Ｃ）として、分離された試料を５秒の間隔で約８３μｌづつ分画し、全３６画分を分取した。
前記工程（Ｄ）として、図２に示すクロマトグラムを解析し、工程（Ｃ）で分取された各画分の重量分率を求めた。
前記工程（Ｅ）として、各画分について、ＭＡＬＤＩ−ＴＯＦＭＳ測定し、マススペクトルを得た。図３には、一例として、溶出時間２１．３分付近で分取された画分のマススペクトルを示す。
前記工程（Ｆ）として、マススペクトルを解析し、各ピークの質量／電荷比（ｍ／ｚ）から分子量を決定した。すなわち、ＭＳ測定に際して、カチオン化剤としてトリフルオロ酢酸銀を使用したことから、観測されたイオンは銀カチオンの付加体であるので、各成分の分子量は、各ピークのｍ／ｚ値から銀カチオンの質量数１０７．９を引いた値である。
前記工程（Ｇ）として、式（９）により、前記工程（Ｅ）で得られたマススペクトルの信号強度を数分率に比例した値に補正する係数ｋ’_ｆを求めた。
前記工程（Ｈ）として、前記工程（Ｄ）から（Ｇ）までの操作を、前記工程（Ｃ）で分取された全３６画分について行った。
前記工程（Ｉ）として、式（１１）により、複数の画分に存在している各成分の数分率に比例する値の総和を求め、さらに式（１２）により、各成分の数分率を求めた。この結果から、絶対分子量分布、絶対平均分子量、組成、及び構成成分ごとの溶出挙動を解析した結果を以下に示す。
【００３８】
（３）−１絶対分子量分布
上記の工程によって求められた各成分の数分率を分子量に対してプロットして得られた、ポリスチレン混合試料の絶対分子量分布を図４に示す。また、比較のために、図５に従来技術のＳＥＣ−ＭＳにより解析された結果を示す。ここで、図５ａは従来技術のＳＥＣ−ＭＳにより得られた図２のクロマトグラムの較正曲線を示したものであり、図５ｂはその較正曲線を用いて解析された分子量分布を示したものである。図４及び図５ｂのいずれにおいても、二峰性の分子量分布が観測されており、低分子量側がポリスチレン▲１▼に、高分子量側がポリスチレン▲２▼に対応している。本実施例で用いたポリスチレン▲１▼及び▲２▼の分子量分布はほとんど重複しないことが予め分っているものであるが、従来技術による場合（図５ｂ）では、分子量分布の大きな重複が認められている。これは、ＳＥＣ分離に際して、流路内における拡散や分離カラム内における相互作用など好ましくない効果により、図５ａに示したようにクロマトグラム上で各ピークが大きく重なり、さらに較正曲線が大きく屈曲していることを原因としている。一方、本発明の方法（図４）では、ポリスチレン▲１▼と▲２▼の分子量分布は明瞭に分離されている。これは、ＳＥＣ分離で好ましくない効果が起こっても、本発明の方法ではＳＥＣクロマトグラムの較正を行わないために、その影響を受けることなく解析できることを明示している。
【００３９】
（３）−２絶対均分子量
図４に示す絶対分子量分布から、ポリスチレン▲１▼及び▲２▼の絶対平均分子量を解析した結果、
ポリスチレン▲１▼：Ｍ_ｎ＝１．００×１０^４、Ｍ_ｗ＝１．０１×１０^４、Ｍ_ｗ／Ｍ_ｎ＝１．０１
ポリスチレン▲２▼：Ｍ_ｎ＝１．７８×１０^４、Ｍ_ｗ＝１．７９×１０^４、Ｍ_ｗ／Ｍ_ｎ＝１．０１
であり、製造者より提供された参照値とよく一致した値が求められた。特に、本発明によるＭ_ｗ値は、絶対平均分子量を測定する光散乱法による参照値と非常によく一致していることは注目に値し、本発明による方法が正確な絶対平均分子量を与えるものであることを明示している。
【００４０】
（３）−３高分子重合物を構成する成分の組成の測定方法
図４に示す分子量分布の各点（○）は重合度が異なる各成分に対応しており、縦軸はその組成（ｍｏｌ％）である。すなわち、図４は、本発明の方法により、高分子重合物を構成する各成分の組成を求めることができることを示している。一方、従来技術によるＳＥＣ−ＭＳでは、ＳＥＣクロマトグラムの横軸を分子量に変換しただけであるので、各成分ごとの組成を求めることはできない。
本発明の方法による組成分析の妥当性を確認するために、図４の結果に基づいてポリスチレン▲１▼及び▲２▼の組成を解析したところ、
ポリスチレン▲１▼：ポリスチレン▲２▼＝６１：３９（モル比）
であり、仕込みより計算される参照値（６４：３６モル比）とよく一致しており、ほぼ正確に組成が定量できることが分った。
【００４１】
（３）−４構成成分ごとの溶出挙動
本発明の方法では、高分子重合物を構成する成分ごとのＳＥＣ分離に際する溶出挙動を解析することができることも特徴としている。その例として、図６にポリスチレンの９５量体（分子量１００６０）と１７０量体（分子量１７８７０）の溶出挙動を示す。いずれの成分とも、ピークの幅広がりとテーリングが観測されている。ピークの幅広がりは、流路内での拡散に起因し、テーリングは分離カラム内における相互作用によるものであると考えられる。このような解析を行うことによって、ＳＥＣの分離条件や分離カラムの性能を詳細に評価することが可能になる。
【００４２】
【発明の効果】
本発明によれば、高分子重合物の平均分子量及び分子量分布において、ＳＥＣ−ＭＳによって分析する際に問題となっていた、ＳＥＣ分離における流路内での拡散や分離カラム内での相互作用などの好ましくない効果による影響を受けることなく、絶対分子量分布、絶対平均分子量、及び組成を正確に測定することを可能にする。さらに、本発明によるＳＥＣ−ＭＳでは、複数の同族体列からなる高分子重合物について、同族体列ごとの絶対分子量分布、絶対平均分子量、及び組成の測定まで可能としている。また、高分子重合物の構成成分ごとの溶出挙動を解析することによって、ＳＥＣの分離条件や分離カラムの性能を詳細に評価することが可能になる。
【図面の簡単な説明】
【図１】本発明の方法を実施する装置構成の一例を示す図
【図２】ポリスチレン混合試料のＳＥＣクロマトグラムを示す図
【図３】ポリスチレン混合試料について分取された画分のマススペクトルの一例を示す図
【図４】本発明の方法により解析されたポリスチレン混合試料の絶対分子量分布を示す図。
【図５】従来技術による比較例を示す図図５ａは、従来技術によるＳＥＣ−ＭＳにおけるＳＥＣクロマトグラムと較正曲線である。図５ｂは、その較正曲線を用いて解析されたポリスチレン混合試料の分子量分布を示す図
【図６】ＳＥＣ分離におけるポリスチレン混合試料の溶出挙動を、分子量の異なる成分ごとに解析した結果を示す図
【符号の簡単な説明】
ＡＳＥＣ装置
１移動相貯留槽
２送液ポンプ
３オートサンプラー
４カラムオーブン
５分離カラム
６ＲＩ検出器
７排出口
ＢＭＳ装置
９試料プレート
１０試料室
１１紫外レーザー
１２引き出し電極
１３フライトチューブ
１４マルチチャンネル検出器
Ｃデータの処理装置
１５ＭＳ用データ処理装置
８ＳＥＣ用データ処理装置
１６ＳＥＣとＭＳのデータを受けて、両者を併せてデータ処理するためのデータ処理装置[0001]
TECHNICAL FIELD OF THE INVENTION
The present invention relates to a method and an apparatus for analyzing a polymer, and more particularly, a method and an apparatus for measuring the absolute molecular weight distribution and the absolute average molecular weight of a polymer and the composition of components constituting the polymer. About.
[0002]
[Prior art]
The high molecular weight polymer is obtained by polymerizing a single component or a plurality of monomer components. The molecular weight of the polymer compound is expressed in a specific range according to the components constituting the polymer compound. For example, in the case of polyethylene, the composition ratio is expressed according to the molecular weight, such as what percentage of a specific molecular weight and what percentage of a specific molecular weight, and the molecular weight is represented as a distribution. In addition, for a plurality of monomers, for example, a copolymer composed of acrylonitrile and butadiene, for the constituent acrylonitrile and butadiene, the numerical value of the molecular weight according to the composition ratio according to the molecular weight is calculated and expressed, and the number average Expressed as average molecular weight or molecular weight distribution such as molecular weight or weight average molecular weight. Polymers are roughly classified into natural high molecular weight polymers and synthetic high molecular weight polymers according to their origin, but the same is true in terms of molecular weight expressed as an average molecular weight or a molecular weight distribution. As described above, a high molecular weight polymer has a molecular weight distribution due to statistical coincidence in the synthesis process, and this greatly affects various properties and characteristics of the high molecular weight polymer. The measurement is very important in understanding the characteristics of the polymer and performing quality control and performance evaluation. For this purpose, various methods for measuring the molecular weight have been studied.
[0003]
Conventionally, SEC has been used as a method for relatively easily measuring the average molecular weight and the molecular weight distribution of a polymer. In the case of using SEC, when a sample solution in which a high molecular weight polymer is dissolved is passed through a separation column filled with a gel-like filler having pores, the filler has a small molecular weight (size). However, since the portion having a high molecular weight (size) which easily enters the inside of the pores of the gel is hard to enter the inside of the pores of the gel, the state in which the high-molecular polymer is taken into the filler is different. When trying to elute the incorporated polymer compound, the smaller the molecular size, the longer the elution time from the separation column. Utilizing this phenomenon, the components separated for each molecular size by the separation column can be separated using a differential refraction detector (hereinafter, referred to as RI detector) or an ultraviolet-visible spectroscopic detector (hereinafter, referred to as UV detector). Observe the chromatogram by detecting. Thus, the distribution according to the molecular weight can be examined.
The molecular weight distribution of the high molecular weight polymer can be analyzed from the chromatogram observed by SEC, and the chromatogram is based on the diffusion phenomenon of the sample in the flow path of the SEC device, the filler in the separation column, and the It is greatly affected by various unavoidable factors such as the pore size distribution, the interaction such as adsorption or repulsion generated between the filler and the material constituting the flow path and the sample, and the degree of the effect is high. It is said to differ depending on the type, molecular weight, molecular weight distribution, concentration, etc. of the molecular polymer (Non-Patent Document 1). Therefore, it is important to reduce the influence of the above factors as much as possible. In this technical field, by examining the type of the mobile phase solvent of SEC (Patent Document 1, Patent Document 2, Patent Document 3, The above-mentioned reduction has been carried out by examining literature 4, patent literature 5, patent literature 6) or a method of preparing a calibration curve (patent literature 7). However, these methods have a problem that it is difficult to completely cancel the above factors, and the reliability of the obtained analysis value is low for the following reasons.
That is, the analysis of the average molecular weight of a high molecular weight polymer using SEC is obtained by measuring a plurality of standard substances having known average molecular weights and plotting the elution time of each standard substance and the logarithm of the average molecular weight. The average amount is determined only by calibrating the chromatogram of the measurement sample using the calibration curve obtained. For this purpose, it is desirable that the standard substance has the same molecular structure as the measurement sample.However, standard substances that are generally easily available as commercial products include polystyrene, polymethyl methacrylate, polyethylene glycol, and pullulan. limited. Therefore, the average molecular weight determined by ordinary SEC is not an absolute average molecular weight based on the molecular weight of a sample, but a relative average molecular weight converted by a calibration curve obtained under the conditions of measuring a standard substance. Reliability is low.
[0004]
As another method for measuring the average molecular weight and the molecular weight distribution of the polymer, the components of the polymer are analyzed by MS using a soft ionization method such as matrix-assisted laser desorption ionization or electrospray ionization. There has been proposed a method of measuring the absolute average molecular weight and the absolute molecular weight distribution with high reliability from the distribution of the peak mass number and the peak intensity of each component by separately observing the molecular weight on a mass spectrum [Non-patent Document 2]. However, in soft ionization MS, since high molecular compounds have molecular weight dependence in ionization efficiency and detector sensitivity, etc., samples for which accurate measurement values can be obtained are limited to high molecular polymers with narrow molecular weight distributions. (Non-Patent Document 3).
[0005]
Therefore, as a method to complement the disadvantages of SEC, which requires a standard substance, and soft ionization MS, which can measure only a sample with a narrow molecular weight distribution, fractions having a narrow molecular weight distribution are finely separated by SEC, and they are separated by soft ionization MS. A method has been proposed in which the average molecular weight of the components present in each fraction is determined by analysis, and the absolute average molecular weight is measured by creating a SEC calibration curve using those values (hereinafter referred to as SEC-MS). (Non-Patent Document 4).
This method using SEC-MS is superior to SEC generally used in that the absolute average molecular weight and the absolute molecular weight distribution can be analyzed without using a standard substance. Is a major drawback. Furthermore, in the method using this SEC-MS, the composition of the components constituting the high molecular weight polymer, and for the high molecular weight polymer including a plurality of homologous series, the average molecular weight, the molecular weight distribution, and the molecular weight of each homologous series are reduced. There is a problem that an appropriate composition cannot be obtained.
[0006]
[Patent Document 1] Japanese Patent Application Laid-Open No. 06-317575
[Patent Document 2] JP-A-06-288997
[Patent Document 3] JP-A-06-109715
[Patent Document 4] Japanese Patent Application Laid-Open No. 05-142218
[Patent Document 5] Japanese Patent Application Laid-Open No. 05-142217
[Patent Document 6] Japanese Patent Laid-Open No. 05-087797
[Patent Document 7] JP-A-09-281097
[Non-patent document 1] Size exclusion chromatography, written by Sadao Mori, Kyoritsu Shuppan (1991)
[Non-Patent Document 2] Eur. Mass Spectrom. , 1, 293 (1995)
[Non-Patent Document 3] Rapid Commun. Mass Spectrom. , 9, 453 (1995)
[Non-Patent Document 4] Mass Spectrom. Rev .. , 16, 283 (1997)
[0007]
[Problems to be solved by the invention]
An object of the present invention is to provide a method for measuring the molecular weight and molecular weight distribution of a polymer using SEC-MS, wherein the absolute average molecular weight distribution and the absolute average molecular weight of the polymer which are considered to represent a more actual state are described. Measuring method, measuring method of absolute average molecular weight, absolute molecular weight distribution for each homologous sequence included in the high molecular polymer that is a mixture consisting of a plurality of homologous sequences, absolute average molecular weight, and the components constituting the high molecular weight polymer A method for analyzing a polymer that measures at least one of the compositions, a method for measuring the absolute composition of a component that constitutes the polymer, and a method for measuring the component that constitutes the polymer in the SEC measurement. It is to provide a method for measuring the dissolution behavior.
[0008]
[Means for Solving the Problems]
Therefore, the present inventors have repeatedly studied to overcome the problem of the prior art SEC-MS that the reliability of the measured value depends on the resolution of the SEC, and have been conducted with the prior art SEC-MS. We have invented a new SEC-MS analysis method that does not perform the molecular weight calibration of the chromatogram. Specifically, focusing on the advantage that the detector of the SEC device can accurately analyze the sum of the amounts of the components contained in the fractions, each fraction fractionated by the SEC was obtained by MS measurement. The peak intensity of the mass spectrum is subjected to sensitivity correction based on the SEC detector signal intensity observed for the corresponding fraction, and by adding them together, the molecular weight and substance of each component constituting the high molecular weight polymer are calculated. It has been found that the relationship between the quantities can be analyzed.
[0009]
According to this analysis, since the calculation result of the molecular weight does not depend on the separation ability of SEC, the absolute molecular weight distribution, the absolute average molecular weight, and the composition can be determined without depending on the separation ability of SEC. A high molecular weight polymer composed of a plurality of homologous series having different fine chemical structures such as terminal group chemical structures, and a plurality of high molecular weight polymers, which were not possible except in special cases with SEC and SEC-MS of the prior art. It has become possible to determine the absolute molecular weight distribution, the absolute average molecular weight, and the composition of a high molecular weight polymer containing a plurality of homologous series, such as a high molecular weight blend composed of
[0010]
According to the present invention, the following inventions are provided.
(1) In a method for measuring the absolute molecular weight distribution of a polymer, an analysis method by size exclusion chromatography (hereinafter, also referred to as SEC), an analysis method by a mass spectrometer (hereinafter, also referred to as MS), and these analysis methods The data are subjected to the processes of (A), (B), (C), and (D) by the SEC analysis method, and then the fraction obtained by the process of (C) is subjected to MS. (E) and (F) are performed by the analysis method according to (1). Based on the measurement results obtained in the steps (D), (E), and (F), the processing in the step (G) is performed by data processing. The operation of the step (H) is performed by the analysis method by the SEC, the analysis method by the MS, and the data processing. A method of measuring the absolute molecular weight distribution of a high molecular weight polymer, wherein the measurement result of the analysis method is corrected by the result of the measurement method of the analysis by SEC.
(A) Step of separating high molecular weight polymer by SEC
(B) a step of detecting the high molecular weight polymer separated in the step (A)
(C) a step of continuously separating the high molecular weight polymer separated in the step (A) simultaneously with or immediately after the step (B)
(D) analyzing the number fraction or the weight fraction of the fraction collected in the step (C) from the signal intensity detected in the step (B)
(E) a step of separating the components constituting the high molecular weight polymer present in the fraction collected in the step (C) based on the mass / charge ratio by mass spectrometry and measuring the respective signal intensities;
(F) a step of determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured in the step (E)
(G) By correcting the signal intensity measured in the step (E) based on the analysis in the step (D), the fraction of each component whose molecular weight is determined in the step (F) is proportional to the fraction or the fraction. Of analyzing the values
(H) a step of performing the operations from steps (D) to (G) on all the fractions collected in step (C)
(I) a step of calculating, for each component present in all the fractions analyzed by performing the operation of the step (H), a fraction or a sum of values proportional to the fraction
(2) measuring the molecular weight distribution of the high molecular weight polymer according to (1), wherein the step (B) is based on a method of detecting a signal proportional to the amount of the substance based on a number fraction or a weight fraction. how to.
(3) The method according to (2), wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.
(4) Before the measurement of the mass / charge ratio in the step (E), the method further includes, as a pretreatment, a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization. The method for measuring the molecular weight distribution of a high molecular weight polymer according to (1), which is characterized in that:
(5) The molecular weight of the high molecular weight polymer according to (4), wherein the step (E) is performed using ionization for generating a molecular weight related ion reflecting a molecular weight distribution of a component contained in the fraction. How to measure the distribution.
(6) The ionization method is performed by a matrix assisted laser desorption ionization method, an electrospray ionization method, an electric field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method. A) measuring the molecular weight distribution of the high molecular weight polymer described above.
(7) The step (E) is performed using a mass spectrometry method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. The method for measuring the molecular weight distribution of a high molecular weight polymer according to (1), which is characterized in that:
[0011]
(8) In the method for measuring the absolute average molecular weight of a polymer,
The method comprises an analysis method by SEC, an analysis method by MS, and data processing. The processes of (A), (B), (C), and (D) are performed by the analysis method by SEC, and then the process of (C) is performed. The fractions collected by the above are subjected to the processing of the steps (E) and (F) by the analysis method using MS, and from the measurement results of the steps (D), (E), and (F), G), the operation of the step (H) is performed by the SEC analysis method, the analysis method by the MS, and the data processing, and the processing of the step (I) is performed by the data processing based on these results. A method for measuring the absolute average molecular weight of a high molecular weight polymer, wherein the measurement result of the analysis method according to (1) is corrected by the measurement result of SEC.
(A) Step of separating high molecular weight polymer by SEC
(B) a step of detecting the high molecular weight polymer separated in the step (A)
(C) a step of continuously separating the high molecular weight polymer separated in the step (A) simultaneously with or immediately after the step (B)
(D) analyzing the number fraction or the weight fraction of the fraction collected in the step (C) from the signal intensity detected in the step (B)
(E) a step of separating the components constituting the high molecular weight polymer present in the fraction collected in the step (C) based on the mass / charge ratio by mass spectrometry and measuring the respective signal intensities;
(F) a step of determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured in the step (E)
(G) By correcting the signal intensity measured in the step (E) based on the analysis in the step (D), the fraction of each component whose molecular weight is determined in the step (F) is proportional to the fraction or the fraction. Of analyzing the values
(H) a step of performing the operations from steps (D) to (G) on all the fractions collected in step (C)
(I) a step of calculating, for each component present in all the fractions analyzed by performing the operation of the step (H), a fraction or a sum of values proportional to the fraction
(9) The absolute average molecular weight of the polymer according to (8), wherein the step (B) is based on a method of detecting a signal proportional to the amount of the substance based on a number fraction or a weight fraction. Measuring method.
(10) The method for measuring an absolute average molecular weight of a polymer according to (9), wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.
(11) Before the measurement of the mass / charge ratio in the step (E), a step of further adding a reagent necessary for drying, concentration, dilution, desalting, derivatization, or ionization as a pretreatment is included. (8) The method for measuring an absolute average molecular weight of a polymer according to (8).
(12) The absolute value of the high molecular weight polymer according to (8), wherein the step (E) is performed by using ionization for generating a molecular weight-related ion reflecting a molecular weight distribution of a component contained in the fraction. Method for measuring average molecular weight.
(13) The ionization method is performed by a matrix-assisted laser desorption ionization method, an electrospray ionization method, a field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method (12). A) a method for measuring the absolute average molecular weight of the high molecular weight polymer described in the above.
(14) The step (E) is performed using a mass spectrometry method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. (8) The method for measuring an absolute average molecular weight of a polymer according to (8).
[0012]
(15) The method for measuring the composition of the components constituting the high molecular weight polymer comprises an analysis method by SEC, an analysis method by MS, and data processing, and (A), (B), (C), And (D), and then the fractions collected in the step (C) are subjected to the treatments in the steps (E) and (F) by an analytical method using MS, thereby obtaining (D), From the measurement results of the steps (E) and (F), the processing of the step (G) is performed by data processing, and the operation of the step (H) is performed by the analysis method by SEC, the analysis method by MS, and the data processing, Based on these results, the processing of the step (I) is performed by data processing to correct the measurement result of the analysis method by MS to the composition depending on the molecular weight by the measurement result by the analysis method by SEC. A method for measuring the composition of components constituting a high molecular weight polymer.
(A) Step of separating high molecular weight polymer by SEC
(B) a step of detecting the high molecular weight polymer separated in the step (A)
(C) a step of continuously separating the high molecular weight polymer separated in the step (A) simultaneously with or immediately after the step (B)
(D) analyzing the number fraction or the weight fraction of the fraction collected in the step (C) from the signal intensity detected in the step (B)
(E) a step of separating the components constituting the high molecular weight polymer present in the fraction collected in the step (C) based on the mass / charge ratio by mass spectrometry and measuring the respective signal intensities;
(F) a step of determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured in the step (E)
(G) By correcting the signal intensity measured in the step (E) based on the analysis in the step (D), the fraction of each component whose molecular weight is determined in the step (F) is proportional to the fraction or the fraction. Of analyzing the values
(H) a step of performing the operations from steps (D) to (G) on all the fractions collected in step (C)
(I) a step of calculating, for each component present in all the fractions analyzed by performing the operation of the step (H), a fraction or a sum of values proportional to the fraction
(16) The step (B) comprises detecting a signal proportional to the substance amount based on a number fraction or a weight fraction, wherein the composition of the component constituting the high molecular polymer according to (15) is How to measure.
(17) The method according to (16), wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.
(18) Before the measurement of the mass / charge ratio in the step (E), a step of further adding a reagent necessary for drying, concentration, dilution, desalting, derivatization, or ionization as a pretreatment is included. The method for measuring the composition of a component constituting a high-molecular polymer according to claim 15, wherein
(19) The component constituting the high molecular weight polymer according to (15), wherein the step (E) is performed by ionization for generating a molecular weight-related ion reflecting the molecular weight distribution of the component contained in the fraction. Of measuring the composition of
(20) The polymer polymerization according to (19), wherein the ionization is performed by matrix-assisted laser desorption ionization, electrospray ionization, electric field desorption ionization, plasma desorption ionization, or high-speed particle impact ionization. A method for measuring the composition of components constituting an object.
(21) The step (E) is performed using a mass spectrometric method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a combination thereof. (15) A method for measuring a composition of a component constituting a high molecular polymer according to (15).
[0013]
(22) At least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of a component constituting the high molecular weight polymer for each homologous sequence included in the high molecular weight polymer which is a mixture including a plurality of homologous number sequences. The measurement method includes an analysis method by SEC, an analysis method by MS, and data processing by these analysis methods, and performs the processes of the steps (A), (B), (C) and (D) by the analysis method by SEC. Then, the fractions collected in the step (C) are subjected to the treatments in the steps (E) and (F) by the analysis method using MS, and the fractions obtained in the steps (D), (E) and (F) are analyzed. From the measurement results, the process of (G) is performed by data processing, the analysis method by SEC, the analysis method by MS, and the operation of (H) are performed by data processing. The molecular weight-dependent composition is measured by performing the treatment of (I) by the data processing, and the absolute molecular weight distribution for each homologous series contained in the high molecular weight polymer, which is a mixture of a plurality of homologous series. , Absolute average molecular weight, and at least one of the components constituting the high molecular weight polymer.
(A) Step of separating high molecular weight polymer by SEC
(B) a step of detecting the high molecular weight polymer separated in the step (A)
(C) a step of continuously separating the high molecular weight polymer separated in the step (A) simultaneously with or immediately after the step (B)
(D) analyzing the number fraction or the weight fraction of the fraction collected in the step (C) from the signal intensity detected in the step (B)
(E) a step of separating the components constituting the high molecular weight polymer present in the fraction collected in the step (C) based on the mass / charge ratio by mass spectrometry and measuring the respective signal intensities;
(F) a step of determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured in the step (E)
(G) By correcting the signal intensity measured in the step (E) based on the analysis in the step (D), the fraction of each component whose molecular weight is determined in the step (F) is proportional to the fraction or the fraction. Of analyzing the values
(H) performing the operation from step (D) to (G) on all the fractions collected in step (C),
(I) A sequence of homologs present in the polymer is assigned based on the molecular weight of each component constituting the polymer obtained in the step (F), and a sequence of homologs present in all fractions to be analyzed. The absolute molecular weight distribution and absolute average of each homologous sequence contained in a high molecular weight polymer which is a mixture of a plurality of homologous sequences characterized by calculating the fractional fraction or the sum of values proportional to the fractional fraction for each A method for analyzing a polymer, comprising measuring at least one of a molecular weight and a composition of components constituting the polymer.
(23) The mixture according to (22), wherein the step (B) is based on a method of detecting a signal proportional to a substance amount based on a number fraction or a weight fraction. A method for analyzing a polymer, comprising measuring at least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the polymer in each homologous series contained in the polymer.
(24) The detection is performed by a differential refraction detector or an ultraviolet-visible detector, wherein each homologue sequence contained in the high molecular weight polymer which is a mixture of a plurality of homologue sequences is described. A method for analyzing a high molecular weight polymer, wherein at least one of the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer is measured.
(25) Before measuring the mass / charge ratio in the step (E), the method further includes, as pretreatment, a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization. (22) The absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture comprising a plurality of homologous type sequences according to (22). A method for analyzing a high molecular weight polymer, wherein at least one method is measured.
(26) The method according to (22), wherein the step (E) is performed using ionization that generates a molecular weight-related ion reflecting a molecular weight distribution of a component contained in the fraction. The absolute molecular weight distribution for each homologous series contained in the high molecular weight polymer, which is a mixture, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer are measured by at least one method. Analysis method.
(27) The ionization method is performed by a matrix-assisted laser desorption ionization method, an electrospray ionization method, a field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method. A) the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence included in the high molecular weight polymer which is a mixture of a plurality of homologous number sequences described in the above. Analytical method of high molecular weight polymer measuring method.
(28) The step (E) is performed using a mass spectrometry method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. (22) The absolute molecular weight distribution, the absolute average molecular weight, and the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture comprising a plurality of homologous type sequences according to (22). A method for analyzing a high molecular weight polymer, which measures at least one method among compositions.
[0014]
(29) The method for measuring the elution behavior of each component constituting the high molecular weight polymer comprises an analysis method by SEC, an analysis method by MS, and data processing, and (A), (B), (B) C) and (D), and then the fractions collected by the operation (C) are subjected to the treatments (E) and (F) by an analytical method using MS to obtain the fractions (D) and (F). From the results obtained from E) and (F), the processing of (G) is performed by data processing, the analysis method by SEC, the analysis method by MS, and the processing of (H) by data processing. A method of measuring the dissolution behavior of each component constituting the high molecular weight polymer, wherein the treatment of (I) is performed by the treatment.
(A) Step of separating high molecular weight polymer by SEC
(B) a step of detecting the high molecular weight polymer separated in the step (A)
(C) a step of continuously separating the high molecular weight polymer separated in the step (A) simultaneously with or immediately after the step (B)
(D) performing a step of analyzing the number fraction or the weight fraction of the fraction collected in the step (C) from the signal intensity detected in the step (B);
(E) a step of separating the components constituting the high molecular weight polymer present in the fraction collected in the step (C) based on the mass / charge ratio by mass spectrometry and measuring the respective signal intensities;
(F) a step of determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured in the step (E)
(G) By correcting the signal intensity measured in the step (E) based on the analysis in the step (D), the fraction of each component whose molecular weight is determined in the step (F) is proportional to the fraction or the fraction. Of analyzing the values
(H) performing steps from (D) to (G) on all the fractions fractionated in step (C) to obtain a fraction or several minutes of each component constituting the high molecular weight polymer. A method for measuring the elution behavior of each component constituting a high-molecular polymer in SEC measurement, wherein a value proportional to the ratio is determined with respect to a time when a fraction is collected.
(30) The high-molecular-weight polymer in the SEC measurement according to (29), wherein the step (B) is based on a method of detecting a signal proportional to a substance amount based on a number fraction or a weight fraction. A method for measuring the dissolution behavior of each component.
(31) The method according to (30), wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.
(32) Before the measurement of the mass / charge ratio in the step (E), a step of further adding a reagent necessary for drying, concentration, dilution, desalting, derivatization, or ionization as a pretreatment is included. (29) The method according to (29), wherein the elution behavior of each component constituting the polymer is measured in the SEC measurement.
(33) The polymer polymerization in the SEC measurement according to (29), wherein the step (E) is performed using ionization that generates molecular weight-related ions reflecting the molecular weight distribution of the components contained in the fraction. A method for measuring the dissolution behavior of each component constituting a substance.
(34) The ionization method is performed by a matrix-assisted laser desorption ionization method, an electrospray ionization method, a field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method (33). A) measuring the elution behavior of each component constituting the high molecular weight polymer in the SEC measurement described in the above.
[0015]
(36) An apparatus for measuring the absolute molecular weight distribution of a high molecular weight polymer, which comprises SEC, MS, and a data processor, and performs the processes (A), (B), (C), and (D) by SEC. The apparatus, and then the apparatus for performing the processing of (E) and (F) using MS on the fraction collected in the step (C), and the apparatus of the above (D), (E), and (F) From the obtained results, an apparatus for performing the processing of (G) by the data processing apparatus, an apparatus for performing the processing of (H) including the SEC, MS, and the data processing apparatus, and the processing of (I) of the data processing apparatus from these results An apparatus for measuring the absolute molecular weight distribution of a high molecular weight polymer, comprising an apparatus for correcting an MS measurement result by an SEC measurement result by an apparatus.
(A) Apparatus for separating high molecular weight polymer by SEC
(B) Apparatus for detecting high molecular weight polymer separated by apparatus (A)
(C) An apparatus for continuously separating the high molecular weight polymer separated by the apparatus (A) simultaneously with or immediately after the apparatus (B)
(D) A device for analyzing the number fraction or the weight fraction of the fraction collected by the device (C) from the signal intensity detected by the device (B).
(E) An apparatus that separates each component constituting the high molecular polymer present in the fraction collected by the apparatus (C) based on the mass / charge ratio by mass spectrometry, and measures the respective signal intensities.
(F) An apparatus for determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured by the apparatus (E)
(G) The signal intensity measured by the device (E) is corrected based on the analysis in the step (D), so that the molecular weight is determined by the device (F). To analyze the value
(H) Apparatus for performing the operations from apparatus (D) to (G) for all fractions collected in step (C)
(I) A device for calculating the fractional fraction or the sum of values proportional to the fractional number for each component present in all the fractions analyzed by performing the operation of the device (H).
(37) The device according to (36), wherein the device (B) is a device that detects a signal proportional to a substance amount based on a number fraction or a weight fraction.
A device for measuring the absolute molecular weight distribution of high molecular weight polymers.
(38) The apparatus for measuring an absolute molecular weight distribution of a polymer according to (37), wherein the apparatus for detecting is performed by a differential refraction detector or an ultraviolet-visible detector.
(39) An apparatus including a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment before measuring the mass / charge ratio with the apparatus (E). The apparatus for measuring an absolute molecular weight distribution of a high molecular weight polymer according to (36), wherein
(40) The polymer polymerization according to (39), wherein the apparatus (E) is an apparatus that uses ionization to generate molecular weight-related ions reflecting the molecular weight distribution of components contained in the fraction. A device for measuring the absolute molecular weight distribution of an object.
(41) The apparatus performed by using the ionization is performed by a matrix-assisted laser desorption ionization apparatus, an electrospray ionization apparatus, a field desorption ionization apparatus, a plasma desorption ionization apparatus, or a high-speed particle impact ionization apparatus. An apparatus for measuring the absolute molecular weight distribution of a high molecular weight polymer according to (40).
(42) The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a combination thereof. The apparatus for measuring the absolute molecular weight distribution of a polymer according to claim 36.
[0016]
(43) An apparatus for measuring the absolute average molecular weight of a high molecular weight polymer, which comprises SEC, MS, and a data processor, and performs the processes (A), (B), (C), and (D) by SEC. Apparatus, and then the apparatus for performing the processing of (E) and (F) using MS on the fraction collected by the apparatus of (C), and the apparatus of (D), (E), and (F). From the obtained results, a device for performing the process (G) by the data processing device,
The operation of (H) is performed by using the SEC, the MS, and the data processing device, and the processing device of (I) by the data processing device is used to correct the MS measurement result by the SEC measurement result. An apparatus for measuring the absolute average molecular weight of a high molecular weight polymer.
(A) Apparatus for separating high molecular weight polymer by SEC
(B) Apparatus for detecting high molecular weight polymer separated by apparatus (A)
(C) An apparatus for continuously separating the high molecular weight polymer separated by the apparatus (A) simultaneously with or immediately after the apparatus (B)
(D) A device for analyzing the number fraction or the weight fraction of the fraction collected by the device (C) from the signal intensity detected by the device (B).
(E) An apparatus that separates each component constituting the high molecular polymer present in the fraction collected by the apparatus (C) based on the mass / charge ratio by mass spectrometry, and measures the respective signal intensities.
(F) An apparatus for determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured by the apparatus (E)
(G) The signal intensity measured by the device (E) is corrected based on the analysis by the device (D), so that the molecular weight is determined by the device (F). To analyze the value
(H) a step of performing the operations from the devices (D) to (G) on all the fractions collected by the device (C)
(I) Apparatus for calculating the fractional fraction or the sum of values proportional to the fractional number for each component present in all fractions analyzed by performing the operation of the apparatus (H)
(44) The apparatus (B) according to (43), wherein the apparatus (B) detects a signal proportional to the amount of the substance based on a number fraction or a weight fraction. measuring device.
(45) The apparatus for measuring an absolute average molecular weight of a high molecular weight polymer according to (44), wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.
(46) An apparatus including a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment before measuring the mass / charge ratio with the apparatus (E). The apparatus for measuring an absolute average molecular weight of a high molecular polymer according to (43), further comprising:
(47) The apparatus according to (43), wherein the apparatus (E) is performed using an ionization apparatus that generates molecular weight-related ions reflecting the molecular weight distribution of components contained in the fraction. Measurement device for absolute average molecular weight.
(48) The ionization apparatus is performed by a matrix-assisted laser desorption ionization apparatus, an electrospray ionization apparatus, a field desorption ionization apparatus, a plasma desorption ionization apparatus, or a fast particle impact ionization apparatus (47). A) an apparatus for measuring the absolute average molecular weight of the high molecular weight polymer described in the above.
(49) The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. An apparatus for measuring an absolute average molecular weight of a high molecular weight polymer according to (48), wherein:
[0017]
(50) An apparatus for measuring the composition of components constituting a high molecular weight polymer, which comprises SEC, MS, and a data processing device, and performs the processing of (A), (B), (C), and (D) by SEC , And then the apparatus for performing the processes (E) and (F) using MS on the fraction collected by the apparatus (C), and measuring (D), (E), and (F). From the results obtained from the apparatus, the operation of (H) is performed using the apparatus for performing the processing of (G) by the data processing apparatus, the SEC, the MS, and the data processing apparatus, and from the results, the operation of (I) is performed by the data processing apparatus. An apparatus for measuring a composition of a component constituting a high molecular weight polymer, comprising an apparatus for correcting a composition depending on a molecular weight based on an SEC measurement result based on an MS measurement result by performing a process.
(A) Apparatus for separating high molecular weight polymer by SEC
(B) Apparatus for detecting high molecular weight polymer separated by apparatus (A)
(C) An apparatus for continuously separating the high molecular weight polymer separated by the apparatus (A) simultaneously with or immediately after the apparatus (B)
(D) A device for analyzing the number fraction or the weight fraction of the fraction collected by the device (C) from the signal intensity detected by the device (B).
(E) An apparatus that separates each component constituting the high molecular polymer present in the fraction collected by the apparatus (C) based on the mass / charge ratio by mass spectrometry, and measures the respective signal intensities.
(F) An apparatus for determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured by the apparatus (E)
(G) The signal intensity measured by the device (E) is corrected based on the analysis by the device (D), so that the molecular weight is determined by the device (F). To analyze the value
(H) Apparatus for performing the operations by apparatuses (D) to (G) for all fractions collected by apparatus (C)
(I) Apparatus for calculating the fractional fraction or the sum of values proportional to the fractional number for each component present in all fractions analyzed by performing the operation of the apparatus (H)
(51) The device (B) according to (50), wherein the device (B) is a device that detects a signal proportional to a substance amount based on a number fraction or a weight fraction. Device for measuring composition.
(52) The apparatus for measuring a composition of a component constituting a high molecular polymer according to (51), wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.
(53) An apparatus including a step of performing drying, concentration, dilution, desalting, derivatization, or addition of a reagent necessary for ionization as a pretreatment before measuring the mass / charge ratio with the apparatus (E). An apparatus for measuring the composition of a component constituting a high molecular polymer according to (50), wherein the apparatus is provided with:
(54) The polymer according to (50), wherein the apparatus (E) is performed using an ionization apparatus that generates molecular weight-related ions reflecting the molecular weight distribution of components contained in the fraction. A device for measuring the composition of the constituent components.
(55) The ionization device is performed by a matrix-assisted laser desorption ionization device, an electrospray ionization device, a field desorption ionization device, a plasma desorption ionization device, or a high-speed particle impact ionization device (54). A) a device for measuring the composition of the components constituting the high molecular weight polymer described in the above).
(56) The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a combination thereof. An apparatus for measuring the composition of a component constituting the high-molecular polymer according to (50), which is characterized in that:
[0018]
(57) At least one of the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture composed of a plurality of homologous number sequences. The measuring device is composed of a size exclusion chromatography (hereinafter, SEC), a mass spectrometer (hereinafter, MS) and a data processor, and (A), (B), (C) and (D) are analyzed by the SEC by the analyzer. Then, the fractions collected by the apparatus of (C) are processed by the apparatus of (E) and (F) by the analyzer using MS, and the fractions obtained by the apparatus of (D), (E), and Based on the measurement results obtained by the apparatus (F), the data processing apparatus performs processing using the apparatus (G), and performs SEC, MS, and processing operations using the apparatus (H) using the data processing apparatus. A data processing device that performs a process using the device (I) to correct the composition depending on the molecular weight, wherein each homolog sequence contained in the high molecular weight polymer is a mixture of a plurality of homolog sequences. At least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting a high molecular weight polymer.
(A) Apparatus for separating high molecular weight polymer by SEC
(B) Apparatus for detecting high molecular weight polymer separated by apparatus (A)
(C) An apparatus for continuously separating the high molecular weight polymer separated by the apparatus (A) simultaneously with or immediately after the apparatus (B)
(D) A device for analyzing the number fraction or the weight fraction of the fraction collected by the device (C) from the signal intensity detected by the device (B).
(E) A device that separates each component constituting the high molecular polymer present in the fraction collected by the device (C) based on the mass / charge ratio by a mass spectrometer, and measures each signal intensity.
(F) An apparatus for determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured by the apparatus (E)
(G) The signal intensity measured by the device (E) is corrected based on the analysis by the device (D), so that the molecular weight is determined by the device (F). To analyze the value
(H) performing the processing by the apparatus (D) to the processing by the apparatus (G) on all the fractions collected by the apparatus (C);
(I) A sequence of homologs present in the polymer is assigned based on the molecular weight of each component constituting the polymer obtained in the apparatus (F), and a sequence of homologs present in all fractions to be analyzed. An absolute value for each homologous sequence contained in a high molecular weight polymer, which is a mixture of a plurality of homologous sequences, characterized by comprising a device for calculating a fractional fraction or a sum of values proportional to the fractional fraction for each An apparatus for analyzing a high molecular weight polymer, which measures at least one of a molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the high molecular weight polymer.
(58) The mixture according to (57), wherein the device (B) is a device that detects a signal proportional to a substance amount based on a number fraction or a weight fraction. An apparatus for analyzing a high molecular weight polymer, which measures at least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the high molecular weight polymer for each homologous series contained in the high molecular weight polymer.
(59) The homolog contained in the high molecular weight polymer which is a mixture of a plurality of homologous strings according to (58), wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector. A high molecular weight polymer analyzer for measuring at least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the high molecular weight polymer for each row.
(60) An apparatus including a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment before measuring the mass / charge ratio with the apparatus (E). Wherein the absolute molecular weight distribution, the absolute average molecular weight, and the high molecular weight of each homologous sequence contained in the high molecular weight polymer which is a mixture of a plurality of homologous sequences described in (57) are constituted. A high molecular weight polymer analyzer for measuring at least one of the component compositions.
(61) The plurality of homologous sequences according to (57), wherein the apparatus (E) is performed using an ionization apparatus that generates molecular weight-related ions reflecting the molecular weight distribution of components contained in the fraction. Absolute molecular weight distribution for each homologous series contained in the high molecular weight polymer, which is a mixture consisting of the high molecular weight polymer, the absolute average molecular weight, and at least one of the compositions of the components constituting the high molecular weight polymer are measured. Analysis equipment.
(62) The ionization device is performed by a matrix assisted laser desorption ionization device, an electrospray ionization device, a field desorption ionization device, a plasma desorption ionization device, or a fast particle impact ionization device. A) the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence included in the high molecular weight polymer which is a mixture of a plurality of homologous number sequences described in the above. High molecular weight polymer analyzer for measuring method.
(63) The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a combination thereof. (57) The absolute molecular weight distribution, the absolute average molecular weight, and the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture comprising a plurality of homologous type sequences according to (57). An apparatus for analyzing a high molecular weight polymer, wherein the composition is measured by at least one apparatus in the composition.
[0019]
(64) An apparatus for measuring the elution behavior of each component constituting the high molecular weight polymer, which is composed of SEC, MS, and a data processing device, and is used for (A), (B), (C), and (D) by SEC. (D), (E), and (F), which perform the processing of (E) and (F) using MS on the fraction collected by the apparatus of (C). From the results obtained from the measurement device of (1), a device for performing the process (G) by the data processing device, and a device for measuring the composition depending on the molecular weight by the processing device of (H) and (I). For measuring the composition of the components constituting the high molecular weight polymer.
(A) Apparatus for separating high molecular weight polymer by SEC
(B) Apparatus for detecting high molecular weight polymer separated by apparatus (A)
(C) An apparatus for continuously separating the high molecular weight polymer separated by the apparatus (A) simultaneously with or immediately after the apparatus (B)
(D) analyzing the number fraction or weight fraction of the fraction collected by the device (C) from the signal intensity detected by the device (B),
(E) An apparatus that separates each component constituting the high molecular polymer present in the fraction collected by the apparatus (C) based on the mass / charge ratio by mass spectrometry, and measures the respective signal intensities.
(F) An apparatus for determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured by the apparatus (E)
(G) The signal intensity measured by the device (E) is corrected based on the analysis in the step (D), so that the molecular weight is determined by the device (F). To analyze the value
(H) An apparatus for performing the operations from the steps (D) to (G) on all the fractions collected in the step (C) by using a fraction or a fraction of each component constituting the high molecular weight polymer. A method for measuring the elution behavior of each component constituting a high molecular weight polymer in SEC measurement, characterized by comprising an apparatus for determining a value proportional to the above with respect to the time of fractionation.
(65) The step (B) comprises a method of detecting a signal proportional to the amount of a substance based on a number fraction or a weight fraction to constitute a high molecular weight polymer in SEC measurement according to (64). A method for measuring the dissolution behavior of each component.
(66) The apparatus for measuring the elution behavior of each component constituting a high molecular polymer in the SEC measurement according to (65), wherein the apparatus for detecting is performed by a differential refraction detector or an ultraviolet-visible detector. .
(67) Before the mass / charge ratio is measured by the device (E), a device for performing drying, concentration, dilution, desalting, derivatization, or addition of a reagent necessary for ionization as a pretreatment is provided. An apparatus for measuring an elution behavior of each component constituting a high molecular weight polymer in the SEC measurement according to (64), wherein:
(68) The polymer polymerization in the SEC measurement according to (64), wherein the apparatus (E) is performed using ionization that generates molecular weight-related ions reflecting the molecular weight distribution of components contained in the fraction. A device that measures the dissolution behavior of each component of a product.
(69) The ionization device is performed by a matrix assisted laser desorption ionization device, an electrospray ionization device, a field desorption ionization device, a plasma desorption ionization device, or a high-speed particle impact ionization device. An apparatus for measuring the elution behavior of each component constituting the high molecular weight polymer in the SEC measurement described in (1).
(70) The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a combination thereof. An apparatus for measuring the elution behavior of each component constituting a high molecular polymer in the SEC measurement according to (64), wherein:
[0020]
BEST MODE FOR CARRYING OUT THE INVENTION
An example of an apparatus configuration for implementing the method of the present invention will be described with reference to the drawings.
FIG. 1 is an example of an apparatus for implementing the present invention.
The SEC device (A) includes a mobile phase storage tank 1, a liquid sending pump 2, an autosampler 3, a column oven 4, a separation column 5, an RI detector 6, and an outlet 7. The MS device (B) uses MALDI-TOFMS and includes a sample plate 9, a sample chamber 10, an ultraviolet laser 11, an extraction electrode 12, a flight tube 13, and a multi-channel detector 14.
A data processing device (C) for data obtained from the SEC device (A) and the MS device (B) is connected to each of the devices, and includes a data processing device 15 for MS, a data processing device 8 for SEC, and SEC and MS. And a data processing device 16 for receiving the data and processing the data together.
In this figure, the SEC device and the MS device are physically separated from each other. However, when the device is actually assembled, the separated high-molecular polymer obtained from the outlet 7 (the separated The high molecular weight polymer present in the sample apparatus can be connected to the sample plate 9 of the MS device by means of supplying the sample plate 9 to the sample plate 9. At the connection part, before the mass / charge ratio is measured by the MS device, means for performing drying, concentration, dilution, desalting, derivatization, or addition of a reagent necessary for ionization as a pretreatment is provided. be able to.
[0021]
At the time of SEC measurement and fractionation, the mobile phase is flowed in advance from the mobile phase storage tank 1 by the pump 2 to create a steady state. Next, a sample is injected from the autosampler 3. The injected sample is introduced into the separation column 5 in the column oven 4 by the mobile phase and subjected to molecular weight separation, thereafter detected by the RI detector 6 and discharged from the outlet 7. The mobile phase containing the sample component separated according to the molecular weight is continuously collected at predetermined intervals at the outlet 7, and each fraction is subjected to MS measurement. The data obtained by the RI detector 6 can be processed by the SEC data processor 8 to draw a chromatogram and calculate the weight fraction of each fraction.
[0022]
The SEC process comprises the following steps, and the apparatus of the present invention comprises the following apparatus.
(A) Process and apparatus for separating a polymer by SEC
(B) a step and an apparatus for detecting the high molecular weight polymer separated in the step (A)
(C) A step and an apparatus for continuously separating the high molecular weight polymer separated in the step (A) simultaneously with or immediately after the step (B)
(D) Step and apparatus for analyzing the fraction or weight fraction of the fraction collected in step (C) from the signal intensity detected in step (B)
[0023]
The SEC device and the separation column (the above steps (A) to (C)) may be any as long as a fraction capable of observing a mass spectrum reflecting a molecular weight distribution can be collected. For example, when MALDI-TOFMS is used for the MS device, the molecular weight distribution of the fraction to be measured preferably has a polydispersity (ratio of weight average molecular weight to number average molecular weight) of 1.1 or less (see above). Such a fraction can be obtained relatively easily by fractionating about 10 to 1000 μl under typical separation conditions generally used for SEC measurement for analysis. Can be. The typical separation conditions referred to here are porous styrene-divinylbenzene-based copolymer particles used in ordinary gel permeation chromatography (SEC using an organic solvent) as a filler for a separation column. A porous methacrylate-based copolymer or a porous vinyl alcohol-based copolymer particle used for gel filtration chromatography (SEC using an aqueous solvent) is used, and the average particle diameter thereof is 3 to 30 μm. The inner diameter of the separation column packed with the packing material is in a range of 4.6 to 7.8 mm and the length is in a range of 7.5 to 30 cm. This is the case where the sample solution was injected in the range of 10 to 200 μl into the mobile phase solvent at a flow rate of 0.35 to 1.0 ml / min. Of course, this is a typical example, and the present invention is not limited to this SEC separation condition. In addition, in the present invention, even in the case of separation conditions in which diffusion phenomena in the flow path and interaction between the sample and the column packing material occur to some extent, which are judged to be inappropriate by ordinary SEC measurement, It is permissible that the fraction in which the mass spectrum reflecting the molecular weight distribution is observed satisfies the separation conditions that can be fractionated. It is.
[0024]
The detector of the SEC device (the step (D)) may be any as long as it can obtain a response value proportional to the amount of the substance in each fraction. For example, an RI detector is a preferred detector because it shows a response proportional to the weight fraction of components passing through the detector per unit time regardless of the chemical structure of the sample. Further, the UV detector is a preferable detector when measuring a sample in which a response proportional to a weight fraction or a several fraction of a component passing through the detector per unit time is obtained. Of course, the type of the SEC detector is not limited to the above as long as the intended purpose can be achieved.
[0025]
At the time of MS measurement, as a pretreatment for MS measurement, a sample solution of each fraction is mixed with a matrix agent and a cationizing agent, dropped on the sample plate 9 and dried. Next, the sample plate 9 is introduced into the sample chamber 10 maintained in a high vacuum, and the surface of the mixed crystal of the sample, the matrix agent, and the cationizing agent is irradiated with an ultraviolet laser beam oscillated from the ultraviolet laser 11 to obtain a sample. Ionize molecules. The ions are accelerated by a potential difference between the sample plate 9 and the extraction electrode 12, are mass-separated during the flight through the flight tube 13, and are detected by the multi-channel plate detector 14. This data is processed by the MS data processor 15 to obtain a mass spectrum.
[0026]
As for the MS device, any device capable of obtaining a mass spectrum composed of molecular weight related peaks reflecting the molecular weight distribution of the fractionated fractions may be obtained. As a soft ionization method therefor, a matrix assisted laser desorption ionization method and Apparatus, electrospray ionization method and apparatus, electrolytic desorption ionization method and apparatus, plasma desorption ionization method and apparatus, high-speed particle bombardment method, and the like. Examples of the method and apparatus for separation include a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, or a combination type combining them, but it is possible to achieve the intended purpose. If, for example, the type of ionization method and apparatus, and mass separation unit is not limited to the above, The combination of these is arbitrary. Among these, currently preferred are MALDI-TOFMS combining a matrix-assisted laser desorption ionization method and apparatus with a time-of-flight mass separator, and a quadrupole or time-of-flight mass with an electrospray ionization method and apparatus. It is an ESI-MS combined with a separation unit.
[0027]
The MS process includes the following steps, and the apparatus of the present invention includes the following apparatus.
(D) analyzing the number fraction or the weight fraction of the fraction collected in the step (C) from the signal intensity detected in the step (B)
(E) a step of separating the components constituting the high molecular weight polymer present in the fraction collected in the step (C) based on the mass / charge ratio by mass spectrometry and measuring the respective signal intensities;
(F) a step of determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured in the step (E)
[0028]
The processing device (C) for the data obtained from the SEC device (A) and the MS device (B) receives the MS data processing device 15 and the SEC data processing device 8 and the data of the SEC and the MS, and combines them. It comprises a data processing device 16 for performing data processing. Specifically, it is a step or apparatus for performing the following processing (G) by a data processing apparatus based on the results obtained from the steps or apparatuses (D), (E), and (F).
(G) By correcting the signal intensity measured by the process or the device (E) based on the analysis by the process or the device (D), the fraction of each component whose molecular weight is determined by the process or the device (F) Or a process or device that analyzes a value proportional to a fraction
Then, using the SEC, MS, and data processing device, “(H) the operation from (D) by the process or the device to (G) by the process or the device is performed for all fractions fractionated by the process or the device (C). Or a device or apparatus to perform the above.
Next, based on these results, the processing of (I) is performed by the data processing device to correct the MS measurement results by the SEC measurement results. "(I) Step or apparatus for obtaining a fraction or a sum of values proportional to the fraction for each component present in all fractions analyzed by performing the operation of the step or apparatus (H)".
[0029]
The method of analyzing the absolute molecular weight distribution and the absolute average molecular weight of the high molecular weight polymer according to the method of the present invention will be described.
Using SEC
(A) A step of separating a polymer by SEC.
Specifically, a sample solution of a polymer is injected into a SEC device and separated by a separation column.
Next, (B) a step of detecting the high molecular weight polymer separated by the above (A).
Specifically, a signal proportional to the substance amount of the component separated by the detector is detected, and the SEC chromatogram is measured.
(C) a step of continuously separating the high molecular weight polymer separated in the step (A) simultaneously with or immediately after the step (B)
Specifically, the components that have passed through the detector are continuously collected. Alternatively, the flow path may be divided after the separation column, the component separated in one flow path may be detected, and the other may be fractionated. In any case, it is desirable that the time difference between detection and separation of the separated components is short.
(D) analyzing the number fraction or the weight fraction of the fraction collected in the step (C) from the signal intensity detected in the step (B)
(E) a step of separating each component constituting the high molecular polymer present in the fraction collected in the step (C) based on the mass / charge ratio using MS and measuring the signal intensity of each component;
[0030]
The method of analyzing the absolute molecular weight distribution and the absolute average molecular weight from the obtained SEC chromatogram and mass spectrum is slightly different depending on the characteristics of the detector of the SEC device, and will be described separately for each case.
[Analysis method 1] When the SEC detector shows a response proportional to the amount of substance by fraction
This corresponds to the case where a signal proportional to the number of molecules of the component that has passed through the detector is detected.For example, when a functional group specifically present at the terminal of the polymer is selectively detected by a UV detector. Is mentioned.
The fraction N of the amount of the substance of the component present in a certain fraction f _f Is the number fraction n of the number of molecules of component i present in the fraction _fi Is the sum of

On the other hand, the fraction n _fi Is the peak intensity I of the component i on the mass spectrum observed for the fraction f. _fi Therefore, it is expressed by equation (2).

From Equations (1) and (2), the proportional coefficient k _f Equation (3) for determining

N _f Is determined as the area ratio of the portion corresponding to the fraction f to the total peak area on the SEC chromatogram (the step (D)). _fi Is determined by analysis of the MS measurement (the step (E)) (the step of determining the molecular weight of each component constituting the polymer) from the mass / charge ratio measured in the step (F) and the step (E). So, after all, k _f Can be obtained by calculation (step (G), by correcting the signal intensity measured in step (E) based on the analysis in step (D), to obtain the molecular weight of each component whose molecular weight has been determined in step (F). Process of analyzing fractions or values proportional to fractions)
This k _f Is determined for all the fractions (step (H)).
Since the component i exists in a plurality of fractions, the sum of the fractions of the component i is represented by m _i Then, for each component present in all the fractions analyzed by performing the operation of the step (I) and the step (H) represented by the equation (4), the fraction is proportional to the fraction or the fraction. Step of calculating the sum of the values.)

M obtained in this way _i Is the composition (mol%) of component i.
Molecular weight M of component i _i Is determined from the mass / charge ratio measured for the component i in the step (F), the measurement conditions of the MS measurement, and the like. _i To M _i If plotted against, the absolute molecular weight distribution can be illustrated.
Furthermore, m _i And M _i From the number average molecular weight (M _n ) And weight average molecular weight (M _w ) Can be calculated by equations (5) and (6), respectively.

The polydispersity, which is an index representing the molecular weight distribution, is M _w And M _n It is determined by the ratio of
[0031]
[Analysis method 2] When the SEC detector shows a response proportional to the substance amount by weight fraction
This includes, for example, the case of using an RI detector or the case of using a UV detector set at a wavelength that is specifically absorbed by the monomer unit of the high molecular polymer in the SEC measurement.
The weight fraction W of the substance amount of the component present in a certain fraction f _f Is the number fraction n of the component i present in the fraction _fi And molecular weight M _fi Is proportional to the sum of the products of

Here, a is a proportional coefficient.
On the other hand, the fraction n _fi Is the peak intensity I of the component i on the mass spectrum observed for the fraction f. _fi Therefore, it is expressed by equation (8).

Equation (9) is derived from equations (7) and (8).

W _f Is determined as the area ratio of the portion corresponding to the fraction f to the total peak area on the SEC chromatogram (the step (D)). _fi And M _fi Is determined by analysis of the MS measurement (the step (E)) (the step (F)). _f Can be obtained by calculation (the step (G)). This k ' _f Is determined for all the fractions (step (H)).
Since the component i is present in a plurality of fractions, the sum of its fractions is represented by m _i Then, it is represented by the formula (10) (the step (I)).

However, if the proportionality coefficient a is unknown, m _i Can not be obtained, so once using equation (11), a value m ′ proportional to the sum of the fractions _i Ask for.

Then, according to equation (12), m ′ _i A is eliminated and the composition m of component i _i Is determined as mol%.

M obtained in this way _i To M _i If plotted against, the absolute molecular weight distribution can be illustrated.
For the analysis of the average molecular weight, M _n Expresses equation (5) as M _w Is determined using equation (6). Note that the proportional coefficient a is M _n And M _w Is eliminated in the calculation process of m, so that m in equations (5) and (6) _i M 'instead of _i May be used.
As described above, according to the present invention, the absolute molecular weight distribution, the absolute average molecular weight, and the SEC chromatogram and the mass spectrum can be obtained from the SEC chromatogram and the mass spectrum by any of the

analysis methods

1 and 2 depending on the characteristics of the SEC detector to be used. And composition can be determined
[0032]
The method of measuring the composition of the components constituting the high molecular weight polymer includes an analysis method by SEC, an analysis method by MS, and data processing, and the analysis by SEC includes (A), (B), (C), and (D). ), And then the fractions collected in the step (C) are subjected to the processing in the steps (E) and (F) by an analytical method using MS, thereby obtaining the fractions in the steps (D) and (E). And, from the measurement results of the step (F), the processing of the step (G) is performed by data processing, the analysis method by SEC, the analysis method by MS, and the operation of the step (H) by data processing. By performing the process of step (I) by data processing, the measurement result of the analysis method by MS is corrected by the measurement result by the analysis method by SEC to correct the composition depending on the molecular weight. Measuring the composition of the components constituting the molecular polymer.
[0033]
At least one method for measuring the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture of a plurality of homologous molecular sequences is used. In the following, an analysis method by SEC, an analysis method by MS, and data processing by these analysis methods are included, and the processing by the steps (A), (B), (C), and (D) is performed by the SEC analysis method. Then, the fractions collected in the step (C) are subjected to the treatments in the steps (E) and (F) by the analysis method using MS, and the steps (D), (E), and (F) are performed. Based on the measurement results, the processing of the step (G) is performed by data processing, the analysis method by SEC, the analysis method by MS, and the operation of the step (H) by data processing. By performing the treatment of (I) by the data treatment, the composition depending on the molecular weight is measured, and thereby the absolute molecular weight distribution and the absolute average of each homologous series contained in the high molecular weight polymer which is a mixture composed of a plurality of homologous series At least one of the molecular weight and the composition of the components constituting the polymer is measured.
[0034]
In the method for measuring the elution behavior of each component constituting the high molecular weight polymer, the SEC, MS, and data processing are used to perform the processes (A), (B), (C), and (D) by SEC. The fractions collected by the operation of (C) are subjected to the processing of (E) and (F) using MS, and the results obtained from the measuring devices of (D), (E), and (F) are used. The processing of (G) is performed by the data processing device, the processing of (H) is performed by using the SEC, MS, and the data processing device, and the processing of (I) is performed by the data processing device based on the results. The elution behavior of each component is measured.
[0035]
【Example】
Hereinafter, typical examples of the present invention performed using the above-described apparatus will be described, and the present invention will be described more specifically. These are merely examples for explanation, and the present invention is not limited to these.
Example 1
Samples obtained by mixing two types of SEC standard polystyrene having different molecular weights (commercially available, manufactured by Tosoh Corporation) were analyzed for the absolute average molecular weight, absolute molecular weight distribution, and composition under the following conditions.
(1) Sample preparation
Polystyrene (1): M _n = 9.30 × 10 ³ , M _w = 9.49 × 10 ³ , M _w / M _n = 1.02 (above, by SEC measurement using standard polystyrene for molecular weight calibration), M _w = 1.02 × 10 ⁴ (By light scattering method)
Polystyrene (2): M _n = 1.70 × 10 ⁴ , M _w = 1.71 x 10 ⁴ , M _w / M _n = 1.01 (above, by SEC measurement using standard polystyrene for molecular weight calibration), M _w = 1.81 × 10 ⁴ (By light scattering method)
The above average molecular weight is a reference value provided by the manufacturer (Tosoh Corporation).
1 mg of polystyrene (1) and 1 mg of (2) were mixed and dissolved in 2 ml of chloroform to prepare a sample solution.
(2) Analysis conditions
(2) -1 SEC measurement and fractionation
Measurement device: HLC-8220GPC (manufactured by Tosoh Corporation)
Separation column: TSKgel G-5000Hxl + 3000Hxl + 2000Hxl (manufactured by Tosoh Corporation) Inner diameter: 7.8 mm, length: 30 cm per one
Column temperature: 40 ° C
Mobile phase: chloroform (flow rate: 1 ml / min)
Detector: RI detector (built-in measuring device)
Sample injection volume: 100 μl
Separation interval: 5 seconds (about 83 μl)
[0036]
(2) -2 MALDI-TOFMS measurement
The eluate of each fraction collected was dried and redissolved in 10 μl of chloroform. 1 μl of the mixture, 4 μl of a matrix solution (a solution of 10 mg of disulanol in 1 ml of chloroform) and 1 μl of a cationizing agent solution (a solution of 1 mg of trifluoroacetic acid in 1 ml of acetone) were mixed, and 1 μl of the mixed solution was mixed. It was applied to a sample plate, dried and crystallized. The sample plate was placed in an ionization chamber of Voyager DE-PRO MALDI-TOFMS (manufactured by Applied Biosystems Japan Co., Ltd.) to obtain a mass spectrum. The above-described MALDI-TOFMS measurement was performed on all fractions for which a response was obtained with the RI detector in the SEC measurement.
[0037]
(3) Measurement and analysis process
The process of analyzing the polystyrene mixed sample will be specifically described below.
In the step (A), a polystyrene mixed sample was injected into the mobile phase from the autosampler 3 of the SEC device in FIG.
In the step (B), the separated sample was detected by the RI detector 6, and a chromatogram shown in FIG. 2 was obtained.
In the step (C), the separated sample was fractionated at intervals of 5 seconds by about 83 μl to collect all 36 fractions.
In the step (D), the chromatogram shown in FIG. 2 was analyzed, and the weight fraction of each fraction collected in the step (C) was determined.
In the step (E), each fraction was subjected to MALDI-TOFMS measurement to obtain a mass spectrum. FIG. 3 shows, as an example, a mass spectrum of a fraction collected at an elution time of about 21.3 minutes.
In the step (F), the mass spectrum was analyzed, and the molecular weight was determined from the mass / charge ratio (m / z) of each peak. That is, since silver trifluoroacetate was used as a cationizing agent during the MS measurement, the observed ion was an adduct of silver cation. 107.9 is subtracted from the mass number of 107.9.
In the step (G), a coefficient k ′ for correcting the signal intensity of the mass spectrum obtained in the step (E) to a value proportional to a fraction by equation (9). _f I asked.
As the step (H), the operations from the steps (D) to (G) were performed on all 36 fractions collected in the step (C).
In the step (I), the sum of values proportional to the number fraction of each component present in a plurality of fractions is calculated by equation (11), and the number fraction of each component is calculated by equation (12). I asked. From the results, the results of analyzing the absolute molecular weight distribution, the absolute average molecular weight, the composition, and the elution behavior for each component are shown below.
[0038]
(3) -1 Absolute molecular weight distribution
FIG. 4 shows the absolute molecular weight distribution of the polystyrene mixed sample obtained by plotting the number fractions of each component obtained in the above steps with respect to the molecular weight. For comparison, FIG. 5 shows the result analyzed by SEC-MS of the related art. Here, FIG. 5a shows a calibration curve of the chromatogram of FIG. 2 obtained by the conventional SEC-MS, and FIG. 5b shows a molecular weight distribution analyzed using the calibration curve. is there. In both FIGS. 4 and 5b, a bimodal molecular weight distribution is observed, with the low molecular weight side corresponding to polystyrene (1) and the high molecular weight side corresponding to polystyrene (2). It is known in advance that the molecular weight distributions of the polystyrenes (1) and (2) used in this example hardly overlap, but in the case of the prior art (FIG. 5b), a large overlap of the molecular weight distributions was recognized. Have been. This is because, during SEC separation, due to unfavorable effects such as diffusion in the flow path and interaction in the separation column, each peak greatly overlaps on the chromatogram as shown in FIG. Is caused by that. On the other hand, in the method of the present invention (FIG. 4), the molecular weight distributions of polystyrene (1) and (2) are clearly separated. This clearly indicates that even if an undesired effect occurs in the SEC separation, the method of the present invention can be analyzed without being affected by the calibration of the SEC chromatogram, which is not performed.
[0039]
(3) -2 Absolute molecular weight
As a result of analyzing the absolute average molecular weights of polystyrene (1) and (2) from the absolute molecular weight distribution shown in FIG.
Polystyrene (1): M _n = 1.00 × 10 ⁴ , M _w = 1.01 × 10 ⁴ , M _w / M _n = 1.01
Polystyrene (2): M _n = 1.78 × 10 ⁴ , M _w = 1.79 × 10 ⁴ , M _w / M _n = 1.01
Thus, a value that was in good agreement with the reference value provided by the manufacturer was obtained. In particular, M according to the invention _w It is noteworthy that the values correspond very well with the reference values obtained by light scattering, which measures the absolute average molecular weight, clearly indicating that the method according to the invention gives an accurate absolute average molecular weight. I have.
[0040]
(3) -3 Method for measuring composition of components constituting high molecular weight polymer
Each point (○) of the molecular weight distribution shown in FIG. 4 corresponds to each component having a different degree of polymerization, and the vertical axis represents the composition (mol%). That is, FIG. 4 shows that the composition of each component constituting the high molecular weight polymer can be obtained by the method of the present invention. On the other hand, in the SEC-MS according to the prior art, the horizontal axis of the SEC chromatogram is simply converted into the molecular weight, and therefore the composition of each component cannot be obtained.
In order to confirm the validity of the composition analysis by the method of the present invention, the composition of polystyrene (1) and (2) was analyzed based on the results of FIG.
Polystyrene (1): Polystyrene (2) = 61:39 (molar ratio)
This was in good agreement with the reference value (64:36 molar ratio) calculated from the preparation, and it was found that the composition could be quantified almost accurately.
[0041]
(3) -4 Dissolution behavior for each component
The method of the present invention is also characterized in that the elution behavior at the time of SEC separation for each component constituting the polymer can be analyzed. As an example, FIG. 6 shows the elution behavior of polystyrene 95-mers (molecular weight 10060) and 170-mers (molecular weight 17870). For all the components, peak broadening and tailing are observed. It is considered that the broadening of the peak is caused by diffusion in the channel, and the tailing is due to interaction in the separation column. By performing such an analysis, the SEC separation conditions and the performance of the separation column can be evaluated in detail.
[0042]
【The invention's effect】
According to the present invention, the average molecular weight and molecular weight distribution of a high molecular weight polymer, which have been problematic when analyzed by SEC-MS, such as diffusion in a flow channel in SEC separation and interaction in a separation column Allows accurate measurement of absolute molecular weight distribution, absolute average molecular weight, and composition without being affected by undesired effects. Furthermore, the SEC-MS according to the present invention enables measurement of the absolute molecular weight distribution, the absolute average molecular weight, and the composition of a high molecular weight polymer composed of a plurality of homologous rows. Further, by analyzing the elution behavior for each component of the high molecular weight polymer, it becomes possible to evaluate the SEC separation conditions and the performance of the separation column in detail.
[Brief description of the drawings]
FIG. 1 is a diagram showing an example of an apparatus configuration for implementing a method of the present invention.
FIG. 2 is a diagram showing a SEC chromatogram of a polystyrene mixed sample.
FIG. 3 is a diagram showing an example of a mass spectrum of a fraction collected from a polystyrene mixed sample.
FIG. 4 is a view showing an absolute molecular weight distribution of a polystyrene mixed sample analyzed by the method of the present invention.
FIG. 5a shows a comparative example according to the prior art. FIG. 5a shows a SEC chromatogram and a calibration curve in SEC-MS according to the prior art. FIG. 5b is a diagram showing a molecular weight distribution of a polystyrene mixed sample analyzed using the calibration curve.
FIG. 6 is a diagram showing the results of analyzing the elution behavior of a polystyrene mixed sample in SEC separation for each component having a different molecular weight
[Brief description of reference numerals]
A SEC device
1 Mobile phase storage tank
2 Liquid sending pump
3 Autosampler
4 Column oven
5 Separation column
6 RI detector
7 outlet
B MS equipment
9 Sample plate
10 Sample room
11 Ultraviolet laser
12 Leader electrode
13 Flight Tube
14 Multi-channel detector
C data processing device
Data processing device for 15MS
8 SEC data processor
16 A data processing device for receiving SEC and MS data and processing the data together

Claims

In the method for measuring the absolute molecular weight distribution of a polymer, an analysis method by size exclusion chromatography (hereinafter, also referred to as SEC), an analysis method by a mass spectrometer (hereinafter, also referred to as MS), and data processing by these analysis methods And performing the treatments in the steps (A), (B), (C), and (D) by the SEC analysis method, and then analyzing the fraction collected in the step (C) by MS. Performs the processing in the steps (E) and (F), performs the processing in the step (G) by data processing from the measurement results in the steps (D), (E), and (F), and analyzes the data by SEC. The operation of the step (H) is performed by the method, the analysis method by the MS, and the data processing, and the processing of the step (I) is performed by the data processing based on these results, whereby the separation by the MS is performed. Method of measuring the absolute molecular weight distribution of the polymer polymer, characterized in that the measurement result of the method for correcting the results of the measurement method of analysis by SEC.
(A) a step of separating the polymer by SEC (B) a step of detecting the polymer separated by the step (A) (C) a step of separating the polymer separated by the step (A) Step (D) of continuously fractionating simultaneously or immediately after (B) the number fraction or weight fraction of the fraction fractionated in step (C) is determined from the signal intensity detected in step (B). Analyzing step (E) The components constituting the high molecular polymer present in the fraction collected in step (C) are separated based on the mass / charge ratio by mass spectrometry, and the respective signal intensities are measured. (F) Step of determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured in the step (E) (G) The signal intensity measured in the step (E) is determined by the step (E). By correcting based on the analysis according to D), the process Step (H) of analyzing the fraction or the value proportional to the fraction of each of the components whose molecular weights have been determined in (F) (H) The operations from steps (D) to (G) are separated by step (C) Step (I) Performed on All Fractions Determined By performing the operation of step (H), for each component present in all fractions analyzed, the fractional fraction or the sum of values proportional to the fractional fraction is determined. Process

2. The method for measuring the molecular weight distribution of a high molecular weight polymer according to claim 1, wherein the step (B) is based on a method of detecting a signal proportional to the amount of the substance based on a number fraction or a weight fraction.

3. The method according to claim 2, wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.

Before measuring the mass / charge ratio in the step (E), the method further includes a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. A method for measuring the molecular weight distribution of the high molecular weight polymer according to claim 1.

5. The method according to claim 4, wherein the step (E) is performed by using ionization for generating a molecular weight-related ion reflecting a molecular weight distribution of a component contained in the fraction. how to.

The method according to claim 5, wherein the ionization method is performed by a matrix-assisted laser desorption ionization method, an electrospray ionization method, a field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method. A method for measuring the molecular weight distribution of a polymer.

The step (E) is performed using a mass spectrometry method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. The method for measuring the molecular weight distribution of a high molecular weight polymer according to claim 1.

In a method for measuring the absolute average molecular weight of a polymer,
The method comprises an analysis method by SEC, an analysis method by MS, and data processing. The processes of (A), (B), (C), and (D) are performed by the analysis method by SEC, and then the process of (C) is performed. The fractions collected by the above are subjected to the processing of the steps (E) and (F) by the analysis method using MS, and from the measurement results of the steps (D), (E), and (F), G), the operation of the step (H) is performed by the SEC analysis method, the analysis method by the MS, and the data processing, and the processing of the step (I) is performed by the data processing based on these results. A method for measuring the absolute average molecular weight of a high molecular weight polymer, wherein the measurement result of the analysis method according to (1) is corrected by the measurement result of SEC.
(A) a step of separating the polymer by SEC (B) a step of detecting the polymer separated by the step (A) (C) a step of separating the polymer separated by the step (A) Step (D) of continuously fractionating simultaneously or immediately after (B) the number fraction or weight fraction of the fraction fractionated in step (C) is determined from the signal intensity detected in step (B). Analyzing step (E) The components constituting the high molecular polymer present in the fraction collected in step (C) are separated based on the mass / charge ratio by mass spectrometry, and the respective signal intensities are measured. (F) Step of determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured in the step (E) (G) The signal intensity measured in the step (E) is determined by the step (E). By correcting based on the analysis according to D), the process Step (H) of analyzing the fraction or the value proportional to the fraction of each of the components whose molecular weights have been determined in (F) (H) The operations from steps (D) to (G) are separated by step (C) Step (I) Performed on All Fractions Determined By performing the operation of step (H), for each component present in all fractions analyzed, the fractional fraction or the sum of values proportional to the fractional fraction is determined. Process

9. The method for measuring an absolute average molecular weight of a high molecular weight polymer according to claim 8, wherein the step (B) is based on a method of detecting a signal proportional to a substance amount based on a number fraction or a weight fraction.

The method for measuring an absolute average molecular weight of a high molecular weight polymer according to claim 9, wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.

Before measuring the mass / charge ratio in the step (E), the method further includes a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. A method for measuring the absolute average molecular weight of the polymer according to claim 8.

9. The method according to claim 8, wherein the step (E) is performed by using ionization to generate a molecular weight-related ion reflecting a molecular weight distribution of a component contained in the fraction. Measuring method.

The method according to claim 12, wherein the ionization method is performed by a matrix assisted laser desorption ionization method, an electrospray ionization method, a field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method. A method for measuring the absolute average molecular weight of a polymer.

The step (E) is performed using a mass spectrometry method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. The method for measuring an absolute average molecular weight of a polymer according to claim 8.

The method for measuring the composition of the components constituting the high molecular weight polymer comprises an analysis method by SEC, an analysis method by MS, and data processing, and (A), (B), (C), and (D) by analysis by SEC. ), And then the fractions collected in the step (C) are subjected to the processing in the steps (E) and (F) by an analytical method using MS, thereby obtaining the fractions in the steps (D) and (E). And, from the measurement results of the step (F), the processing of the step (G) is performed by data processing, the analysis method by SEC, the analysis method by MS, and the operation of the step (H) by data processing. From the data processing, the processing of the step (I) is performed to correct the measurement result of the analysis method by MS and the composition dependent on the molecular weight by the measurement result by the analysis method by SEC. Method for measuring the composition of the components constituting the high molecular polymer to symptoms.
(A) a step of separating the polymer by SEC (B) a step of detecting the polymer separated by the step (A) (C) a step of separating the polymer separated by the step (A) Step (D) of continuously fractionating simultaneously or immediately after (B) the number fraction or weight fraction of the fraction fractionated in step (C) is determined from the signal intensity detected in step (B). Analyzing step (E) The components constituting the high molecular polymer present in the fraction collected in step (C) are separated based on the mass / charge ratio by mass spectrometry, and the respective signal intensities are measured. (F) Step of determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured in the step (E) (G) The signal intensity measured in the step (E) is determined by the step (E). By correcting based on the analysis according to D), the process Step (H) of analyzing the fraction or the value proportional to the fraction of each of the components whose molecular weights have been determined in (F) (H) The operations from steps (D) to (G) are separated by step (C) Step (I) Performed on All Fractions Determined By performing the operation of step (H), for each component present in all fractions analyzed, the fractional fraction or the sum of values proportional to the fractional fraction is determined. Process

16. The method for measuring the composition of a component constituting a high molecular polymer according to claim 15, wherein the step (B) detects a signal proportional to the amount of the substance based on a number fraction or a weight fraction. .

17. The method according to claim 16, wherein said detecting is performed by a differential refraction detector or an ultraviolet-visible detector.

Before measuring the mass / charge ratio in the step (E), the method further includes a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. A method for measuring the composition of a component constituting the high molecular weight polymer according to claim 15.

The composition of the component constituting the high-molecular polymer according to claim 15, wherein the step (E) is performed by ionization to generate a molecular weight-related ion reflecting the molecular weight distribution of the component contained in the fraction. How to measure.

20. The polymer of claim 19, wherein the ionization is performed by matrix-assisted laser desorption ionization, electrospray ionization, field desorption ionization, plasma desorption ionization, or fast particle impact ionization. A method for measuring the composition of a component to be used.

The step (E) is performed using a mass spectrometric method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. A method for measuring the composition of a component constituting a high-molecular polymer according to claim 15.

In the method for measuring at least one of the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture comprising a plurality of high molecular weight groups. , SEC analysis method, MS analysis method, and data processing by these analysis methods. The SEC performs the processing of the steps (A), (B), (C) and (D) by the analysis method, The fraction collected in the step (C) is subjected to the processing in the steps (E) and (F) by an analysis method using MS, and the measurement results in the steps (D), (E), and (F) are used. , The process of (G) is performed by data processing, the analysis method by SEC, the analysis method by MS, and the process of (H) are performed by data processing, and the data processing is performed from these measurement results. By performing the treatment (I), the composition depending on the molecular weight is measured, and the absolute molecular weight distribution and the absolute molecular weight distribution for each homologous series contained in the high molecular weight polymer which is a mixture of a plurality of homologous series are characterized. At least one method of measuring the average molecular weight and the composition of the components constituting the polymer.
(A) a step of separating the polymer by SEC (B) a step of detecting the polymer separated by the step (A) (C) a step of separating the polymer separated by the step (A) Step (D) of continuously fractionating simultaneously or immediately after (B) the number fraction or weight fraction of the fraction fractionated in step (C) is determined from the signal intensity detected in step (B). Analyzing step (E) The components constituting the high molecular polymer present in the fraction collected in step (C) are separated based on the mass / charge ratio by mass spectrometry, and the respective signal intensities are measured. (F) Step of determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured in the step (E) (G) The signal intensity measured in the step (E) is determined by the step (E). By correcting based on the analysis according to D), the process Step (H) of analyzing the fraction or the value proportional to the fraction of each of the components whose molecular weights have been determined in (F) (H) The operations from steps (D) to (G) are separated by step (C) Perform the process for all the fractions that have been performed,
(I) A sequence of homologs present in the polymer is assigned based on the molecular weight of each component constituting the polymer obtained in the step (F), and a sequence of homologs present in all fractions to be analyzed. The absolute molecular weight distribution and absolute average of each homologous sequence contained in a high molecular weight polymer which is a mixture of a plurality of homologous sequences characterized by calculating the fractional fraction or the sum of values proportional to the fractional fraction for each A method for analyzing a polymer, comprising measuring at least one of a molecular weight and a composition of components constituting the polymer.

23. The polymer according to claim 22, wherein the step (B) is a method of detecting a signal proportional to a substance amount based on a number fraction or a weight fraction. A method for analyzing a polymer, comprising measuring at least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the polymer in each homologous series contained in the polymer.

The absolute molecular weight of each homologous series contained in a high molecular polymer which is a mixture of a plurality of homologous series according to claim 23, wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector. A method for analyzing a polymer, comprising measuring at least one of distribution, absolute average molecular weight, and composition of components constituting the polymer.

Before measuring the mass / charge ratio in the step (E), the method further includes a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. An absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the high molecular weight polymer for each homologous sequence included in the high molecular weight polymer which is a mixture of a plurality of homologous type sequences according to claim 22. A method for analyzing a high molecular weight polymer, wherein at least one method is measured.

23. The mixture according to claim 22, wherein the step (E) is performed by using ionization to generate a molecular weight-related ion reflecting a molecular weight distribution of a component contained in the fraction. A method for analyzing a polymer, comprising measuring at least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the polymer in each homologous series contained in the polymer.

The method according to claim 26, wherein the ionization method is performed by a matrix assisted laser desorption ionization method, an electrospray ionization method, a field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method. Measuring at least one method among the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous group contained in the high molecular weight polymer which is a mixture comprising a plurality of high molecular weight groups. For analyzing high molecular weight polymers.

The step (E) is performed using a mass spectrometry method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. The absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture comprising a plurality of homologous number sequences according to claim 22. A method for analyzing a high molecular weight polymer, wherein at least one method is measured.

The method for measuring the elution behavior of each component constituting the high molecular weight polymer comprises an analysis method by SEC, an analysis method by MS, and data processing. The analysis method by SEC includes (A), (B), (C), And (D), and then the fractions collected by the operation of (C) are subjected to the processing of (E) and (F) by an analytical method using MS to obtain (D), (E), and From the result obtained by the processing of (F), the processing of (G) is performed by data processing, the analysis method by SEC, the analysis method by MS, and the data processing are (H), and from these results, (I) is obtained by data processing. A method for measuring the dissolution behavior of each component constituting a high molecular weight polymer, which is characterized by performing a treatment.
(A) a step of separating the polymer by SEC (B) a step of detecting the polymer separated by the step (A) (C) a step of separating the polymer separated by the step (A) Step (D) of continuously fractionating simultaneously or immediately after (B) the number fraction or weight fraction of the fraction fractionated in step (C) is determined from the signal intensity detected in step (B). Perform the analysis process,
(E) a step of separating the components constituting the high molecular weight polymer present in the fraction collected in the step (C) based on the mass / charge ratio by mass spectrometry, and measuring the respective signal intensities ( F) Step of determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured in Step (E) (G) The signal intensity measured in Step (E) is determined according to Step (D). Step (H) of analyzing the fraction or the value proportional to the fraction of each component whose molecular weight has been determined in the step (F) by correcting based on the analysis. The operation from the steps (D) to (G). Is performed on all the fractions fractionated in step (C), and the fraction of each component constituting the high molecular weight polymer or a value proportional to the fraction is determined by the fractionation time. For SEC measurement A method for measuring the dissolution behavior of each component constituting the copolymer.

30. For each component constituting the high molecular weight polymer in the SEC measurement according to claim 29, wherein the step (B) is based on a method of detecting a signal proportional to a substance amount based on a number fraction or a weight fraction. Method for measuring the dissolution behavior of water.

The method according to claim 30, wherein the detection is performed by a differential refraction detector or an ultraviolet-visible detector.

Before measuring the mass / charge ratio in the step (E), the method further includes a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. 30. The method for measuring the elution behavior of each component constituting a polymer in the SEC measurement according to claim 29.

30. The polymer according to claim 29, wherein the step (E) is performed by using ionization to generate a molecular weight-related ion reflecting a molecular weight distribution of a component contained in the fraction. A method for measuring the dissolution behavior of each component.

The method according to claim 33, wherein the ionization method is performed by a matrix assisted laser desorption ionization method, an electrospray ionization method, a field desorption ionization method, a plasma desorption ionization method, or a fast particle impact ionization method. A method for measuring the elution behavior of each component constituting a polymer in SEC measurement.

The step (E) is performed using a mass spectrometry method selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. 30. The method for measuring the elution behavior of each component constituting a high molecular polymer in the SEC measurement according to claim 29.

An apparatus for measuring the absolute molecular weight distribution of a high molecular weight polymer, which comprises SEC, MS, and a data processing apparatus, and performs (A), (B), (C), and (D) processing by SEC. And (F) using the MS for the fraction collected in the step (C), and the results obtained from the apparatuses (D), (E) and (F). From the above, an apparatus for performing the processing of (G) by the data processing apparatus, an apparatus for performing the processing of (H) including the SEC, MS, and the data processing apparatus, and a processing apparatus of (I) of the data processing apparatus based on these results. An apparatus for measuring the absolute molecular weight distribution of a high molecular weight polymer, comprising an apparatus for correcting an MS measurement result by an SEC measurement result.
(A) Apparatus for separating high-molecular polymer by SEC (B) Apparatus for detecting high-molecular polymer separated by apparatus (A) (C) Apparatus for separating high-molecular polymer separated by apparatus (A) (D) A device that performs continuous fractionation at the same time as or immediately after (B) (D) The number fraction or weight fraction of the fraction fractionated by the device (C) is determined from the signal intensity detected by the device (B). Analyzing device (E) The components constituting the high molecular weight polymer present in the fraction collected by the device (C) are separated by mass spectrometry based on the mass / charge ratio, and the respective signal intensities are measured. (F) A device for determining the molecular weight of each component constituting the high molecular weight polymer from the mass / charge ratio measured by the device (E) (G) The signal intensity measured by the device (E) is determined by the step ( By correcting based on the analysis according to D), the device (H) A device for analyzing the fractional fraction of each component whose molecular weight has been determined in (F) or a value proportional to the fractional fraction (H) The operations from the devices (D) to (G) are separated by the step (C). Apparatus (I) to be performed on all fractions subjected to operation The apparatus (H) is operated to calculate the fractional fraction or the sum of values proportional to the fractional fraction for each component present in all fractions analyzed by the operation of the apparatus (H). apparatus.

37. The apparatus for measuring the absolute molecular weight distribution of a high molecular weight polymer according to claim 36, wherein the apparatus (B) is an apparatus for detecting a signal proportional to a substance amount based on a number fraction or a weight fraction.

38. The apparatus for measuring the absolute molecular weight distribution of a polymer according to claim 37, wherein the apparatus for detecting is performed by a differential refraction detector or an ultraviolet-visible detector.

Before the mass / charge ratio is measured by the device (E), an apparatus is provided which further comprises a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. 37. The apparatus for measuring the absolute molecular weight distribution of a polymer according to claim 36, wherein:

The absolute polymer polymer according to claim 39, wherein the apparatus (E) is an apparatus that uses ionization to generate a molecular weight-related ion reflecting a molecular weight distribution of a component contained in the fraction. Measurement device for molecular weight distribution.

The apparatus performed using the ionization is performed by a matrix-assisted laser desorption ionization apparatus, an electrospray ionization apparatus, a field desorption ionization apparatus, a plasma desorption ionization apparatus, or a fast particle impact ionization apparatus. An apparatus for measuring the absolute molecular weight distribution of a polymer according to claim 40.

The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. The apparatus for measuring the absolute molecular weight distribution of a polymer according to claim 36.

An apparatus for measuring the absolute average molecular weight of a high molecular weight polymer, which comprises SEC, MS, and a data processor, and performs (A), (B), (C), and (D) processing by SEC. And (F) using the MS for the fractions collected by the (C) apparatus, and the results obtained from the (D), (E), and (F) apparatuses. A device for performing the processing of (G) by the data processing device,
The operation of (H) is performed by using the SEC, the MS, and the data processing device, and the processing device of (I) by the data processing device is used to correct the MS measurement result by the SEC measurement result. An apparatus for measuring the absolute average molecular weight of a high molecular weight polymer.
(A) Apparatus for separating high-molecular polymer by SEC (B) Apparatus for detecting high-molecular polymer separated by apparatus (A) (C) Apparatus for separating high-molecular polymer separated by apparatus (A) (D) A device that performs continuous fractionation at the same time as or immediately after (B) (D) The number fraction or weight fraction of the fraction fractionated by the device (C) is determined from the signal intensity detected by the device (B). Analyzing device (E) The components constituting the high molecular weight polymer present in the fraction collected by the device (C) are separated by mass spectrometry based on the mass / charge ratio, and the respective signal intensities are measured. (F) A device for determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured by the device (E) (G) The signal intensity measured by the device (E) is measured by the device ( By correcting based on the analysis according to D), the device (H) A device for analyzing the fractional fraction of each component whose molecular weight has been determined in (F) or a value proportional to the fractional fraction (H) The operations from the devices (D) to (G) are separated by the device (C). Step (I) to be performed on all the fractions obtained by the operation of the apparatus (H) For each component present in all the fractions analyzed by the operation of the apparatus (H), the fractional fraction or the sum of values proportional to the fractional fraction is obtained. apparatus

44. The apparatus for measuring an absolute average molecular weight of a high molecular weight polymer according to claim 43, wherein the apparatus (B) is an apparatus for detecting a signal proportional to the amount of the substance based on a number fraction or a weight fraction.

45. The measuring apparatus for measuring an absolute average molecular weight of a polymer according to claim 44, wherein the detecting device is performed by a differential refraction detector or an ultraviolet-visible detector.

Before the mass / charge ratio is measured by the device (E), an apparatus is provided which further comprises a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. The apparatus for measuring an absolute average molecular weight of a high molecular weight polymer according to claim 43, wherein:

44. The absolute average molecular weight of the high molecular weight polymer according to claim 43, wherein the apparatus (E) is performed using an ionizer that generates molecular weight related ions reflecting the molecular weight distribution of components contained in the fraction. Measuring device.

48. The method of claim 47, wherein the ionization is performed by a matrix assisted laser desorption ionizer, an electrospray ionizer, a field desorption ionizer, a plasma desorption ionizer, or a fast particle impact ionizer. Measurement device for absolute average molecular weight of high molecular weight polymer.

The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. 49. An apparatus for measuring the absolute average molecular weight of a polymer according to claim 48.

An apparatus for measuring the composition of components constituting a high molecular weight polymer, which comprises SEC, MS, and a data processor, and performs the processing of (A), (B), (C), and (D) by SEC Then, the fractions collected by the apparatus of (C) are obtained from the apparatus for performing the processing of (E) and (F) using MS and the measuring apparatuses of (D), (E), and (F). Based on the result obtained, the operation of (H) is performed using the device that performs the processing of (G) by the data processing device, the SEC, the MS, and the data processing device, and the processing of (I) is performed by the data processing device based on these results. An apparatus for measuring the composition of components constituting a high molecular weight polymer, comprising an apparatus for correcting a composition dependent on a molecular weight based on an MS measurement result based on an MS measurement result.
(A) Apparatus for separating high-molecular polymer by SEC (B) Apparatus for detecting high-molecular polymer separated by apparatus (A) (C) Apparatus for separating high-molecular polymer separated by apparatus (A) (D) A device that performs continuous fractionation at the same time as or immediately after (B) (D) The number fraction or weight fraction of the fraction fractionated by the device (C) is determined from the signal intensity detected by the device (B). Analyzing device (E) The components constituting the high molecular weight polymer present in the fraction collected by the device (C) are separated by mass spectrometry based on the mass / charge ratio, and the respective signal intensities are measured. (F) A device for determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured by the device (E) (G) The signal intensity measured by the device (E) is measured by the device ( By correcting based on the analysis according to D), the device (H) A device for analyzing the fractional fraction of each component whose molecular weight is determined in (F) or a value proportional to the fractional ratio (H) The operation by the device (D) to the operation by (G) is separated by the device (C). (I) Apparatus for calculating all fractions for each component present in all fractions analyzed by performing operation of apparatus (H) for calculating fractional fractions or sums of values proportional to fractional fractions

51. The composition of a component constituting a high-molecular polymer according to claim 50, wherein the device (B) is a device that detects a signal proportional to a substance amount based on a number fraction or a weight fraction. apparatus.

52. The apparatus for measuring a composition of a component constituting a high molecular polymer according to claim 51, wherein the apparatus for detecting is performed by a differential refraction detector or an ultraviolet-visible detector.

Before the mass / charge ratio is measured by the device (E), an apparatus is provided which further comprises a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. An apparatus for measuring a composition of a component constituting a high-molecular polymer according to claim 50.

52. The component constituting the high molecular weight polymer according to claim 50, wherein the device (E) is performed using an ionization device that generates a molecular weight related ion reflecting the molecular weight distribution of the component contained in the fraction. For measuring the composition of

55. The method according to claim 54, wherein the ionization device is performed by a matrix assisted laser desorption ionization device, an electrospray ionization device, a field desorption ionization device, a plasma desorption ionization device, or a fast particle impact ionization device. A device for measuring the composition of components constituting a high-molecular polymer.

The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. An apparatus for measuring the composition of a component constituting a high-molecular polymer according to claim 50.

In at least one measuring device of the absolute molecular weight distribution, the absolute average molecular weight, and the composition of components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular weight polymer which is a mixture comprising a plurality of high molecular weight groups. , A size exclusion chromatography (hereinafter, SEC), a mass spectrometer (hereinafter, MS) and a data processing device,
The processing by the apparatus of (A), (B), (C) and (D) is performed by the analyzer by SEC, and the fraction collected by the apparatus of (C) is then processed by the analyzer by MS (E). And (F), the data processing apparatus (G) performs the processing based on the measurement results obtained by the (D), (E), and (F) apparatuses, and performs SEC, MS, and data processing. A plurality of homologues characterized by correcting the composition depending on the molecular weight by performing the processing operation of the apparatus (H) by the apparatus and performing the processing of the apparatus (I) by the data processing apparatus from the measurement results. At least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the high molecular weight polymer for each homologous group contained in the high molecular weight polymer which is a mixture of the high molecular weight polymer;
(A) Apparatus for separating high-molecular polymer by SEC (B) Apparatus for detecting high-molecular polymer separated by apparatus (A) (C) Apparatus for separating high-molecular polymer separated by apparatus (A) (D) A device that performs continuous fractionation at the same time as or immediately after (B) (D) The number fraction or weight fraction of the fraction fractionated by the device (C) is determined from the signal intensity detected by the device (B). Device for analysis (E) The components constituting the high molecular weight polymer present in the fraction collected by the device (C) are separated by a mass spectrometer based on the mass / charge ratio, and the signal intensity of each component is determined. Apparatus for measuring (F) Apparatus for determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured by the apparatus (E) (G) The signal intensity measured by the apparatus (E) is measured. By correcting based on the analysis by (D), A device (H) for analyzing a fraction or a value proportional to the fraction of each component whose molecular weight is determined by the device (F) (H) The operation by the processing from the devices (D) to (G) is performed by the device (C) Perform processing by the device that performs on all fractions fractionated by
(I) A sequence of homologs present in the polymer is assigned based on the molecular weight of each component constituting the polymer obtained in the apparatus (F), and a sequence of homologs present in all fractions to be analyzed. An absolute value for each homologous sequence contained in a high molecular weight polymer, which is a mixture of a plurality of homologous sequences, characterized by comprising a device for calculating a fractional fraction or a sum of values proportional to the fractional fraction for each An apparatus for analyzing a high molecular weight polymer, which measures at least one of a molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the high molecular weight polymer.

58. The polymer according to claim 57, wherein the device (B) is a device for detecting a signal proportional to a substance amount based on a number fraction or a weight fraction. A high molecular weight polymer analyzer for measuring at least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting a high molecular weight polymer for each homologous series contained in the polymer.

The apparatus for detection is performed by a differential refraction detector or an ultraviolet-visible detector, wherein each homologous sequence contained in the high molecular weight polymer is a mixture of a plurality of homologous sequences according to claim 58. A high molecular weight polymer analyzer for measuring at least one of an absolute molecular weight distribution, an absolute average molecular weight, and a composition of components constituting the high molecular weight polymer.

Before the mass / charge ratio is measured by the device (E), a device is provided which further includes a step of drying, concentrating, diluting, desalting, derivatizing, or adding a reagent necessary for ionization as a pretreatment. The absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular polymer which is a mixture comprising a plurality of homologous sequences according to claim 57. A high molecular weight polymer analyzer for measuring at least one of the following.

58. The mixture comprising a plurality of homologous rows according to claim 57, wherein the apparatus (E) is performed using an ionization apparatus that generates molecular weight-related ions reflecting the molecular weight distribution of components contained in the fraction. A high molecular weight polymer analyzer for measuring at least one of the absolute molecular weight distribution, the absolute average molecular weight, and the composition of components constituting the high molecular weight polymer for each homologous series contained in the high molecular weight polymer.

62. The ionizer of claim 61, wherein the ionizer is a matrix assisted laser desorption ionizer, electrospray ionizer, field desorption ionizer, plasma desorption ionizer, or fast particle impact ionizer. Measuring at least one method among the absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous group contained in the high molecular weight polymer which is a mixture comprising a plurality of high molecular weight groups. Of high molecular weight polymer.

The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. The absolute molecular weight distribution, the absolute average molecular weight, and the composition of the components constituting the high molecular weight polymer for each homologous sequence contained in the high molecular polymer which is a mixture comprising a plurality of homologous sequences according to claim 57. An apparatus for analyzing a high molecular weight polymer, which is measured by at least one apparatus of the above.

An apparatus for measuring the dissolution behavior of each component constituting a high molecular weight polymer, which comprises SEC, MS, and a data processing device, and performs the processes (A), (B), (C), and (D) by SEC. The apparatus which performs the processing of (E) and (F) using MS on the fraction collected by the apparatus of (C), and the measuring apparatus of (D), (E) and (F) From the results obtained from (1), a polymer for performing the processing of (G) by the data processing apparatus, and a apparatus for measuring the composition depending on the molecular weight by the processing apparatuses of (H) and (I). An apparatus for measuring the composition of components constituting a polymer.
(A) Apparatus for separating high-molecular polymer by SEC (B) Apparatus for detecting high-molecular polymer separated by apparatus (A) (C) Apparatus for separating high-molecular polymer separated by apparatus (A) (D) A device that performs continuous fractionation at the same time as or immediately after (B) (D) The number fraction or weight fraction of the fraction fractionated by the device (C) is determined from the signal intensity detected by the device (B). Perform the analysis process,
(E) An apparatus that separates each component constituting the high molecular weight polymer present in the fraction collected by the apparatus (C) based on the mass / charge ratio by mass spectrometry, and measures each signal intensity ( F) A device (G) for determining the molecular weight of each component constituting the high molecular polymer from the mass / charge ratio measured by the device (E). The signal intensity measured by the device (E) is determined by the step (D). A device for analyzing a fraction or a value proportional to the fraction of each component whose molecular weight is determined by the device (F) by correcting based on the analysis (H) An operation from the steps (D) to (G) Is carried out on all the fractions fractionated in step (C) by using the fraction of each component constituting the high molecular weight polymer or a value proportional to the fraction to the time at which the fraction was fractionated. SE comprising a device required for A method for measuring the elution behavior of each component constituting the high molecular weight polymer in the C measurement.

65. For each component constituting the high molecular weight polymer in the SEC measurement according to claim 64, wherein the step (B) is a method of detecting a signal proportional to a substance amount based on a number fraction or a weight fraction. Method for measuring the dissolution behavior of water.

66. The apparatus for measuring the elution behavior of each component constituting a polymer in SEC measurement according to claim 65, wherein the apparatus for detecting is performed by a differential refraction detector or an ultraviolet-visible detector.

Before measuring the mass / charge ratio with the device (E), it is necessary to provide a device for adding a reagent necessary for drying, concentration, dilution, desalting, derivatization, or ionization as a pretreatment. The apparatus for measuring the elution behavior of each component constituting a polymer in SEC measurement according to claim 64.

65. The high molecular weight polymer in the SEC measurement according to claim 64, wherein the apparatus (E) is performed using ionization for generating a molecular weight related ion reflecting a molecular weight distribution of a component contained in the fraction. For measuring the dissolution behavior of each component.

69. The ionizer of claim 68, wherein the ionizer is a matrix assisted laser desorption ionizer, electrospray ionizer, field desorption ionizer, plasma desorption ionizer, or fast particle impact ionizer. An apparatus for measuring the elution behavior of each component constituting a high molecular weight polymer in SEC measurement.

The apparatus (E) is performed using a mass spectrometer selected from the group consisting of a time-of-flight type, a quadrupole type, an ion trap type, a sector type, a Fourier transform type, and a composite type thereof. 65. An apparatus for measuring elution behavior of each component constituting a high molecular polymer in SEC measurement according to claim 64.