201232598 六、發明說明： 【發明所屬之技術領域】 本發明有關於-種用於液相層析質譜儀的轉換組件，特別 是指-種用於將液相層析質譜儀的電喷麟離裝置轉換為大 氣壓化學游離裝置的轉換組件，以及一種使用該轉換組件的游 離裝置。 【先前技術】 由於液相層析質譜儀（Liquid Chromatography-Mass Spectrometer，LC/MS)具有靈敏度高以及選擇性佳的優點，因此 近年來已成為分析生物樣品最主要的儀器，並廣泛地應用於諸 如食品中之維生素、防腐劑、農藥、生長激素以及有害添加劑 含量的檢測；生物體的藥物代謝分析、疾病的筛檢以及人體内 毒品含量的檢測等。 液相層析質譜儀（LC/MS)主要是將液相層析儀(Liquid Chromatography, LC)與質譜儀(Mass Spectr〇meter，MS)結合，透 過液相層析儀分離出樣品中的待測物，再利用質譜儀進行分 析。質譜儀主要包括有-游離裝置、一質量分析器以及一偵測 器，並且，依據樣品的物理與化學特性不同，適用的游離裝置 也不相同，一般而言’當待測物極性較高時，通常使用電喷灑 游離(electrospmy i〇nization，ESI)裝置；而當待測物為中、低 極丨生時，則夕使用大氣壓力化學游離(atm〇spheric chemical ionization，APCI)裝置。 第一圖所示者，為商業化電喷灑游離裝置1〇的游離機制 201232598 示意圖’電喷灑游離裝置ίο具有一喷頭⑴彳 貝頌Wp) u，其内穿設有 (metal capillary) 13 , ~^,ta||(Nebulizer201232598 VI. Description of the Invention: [Technical Field] The present invention relates to a conversion component for a liquid chromatography mass spectrometer, and more particularly to an electrospray ionization of a liquid chromatography mass spectrometer The device converts to a conversion assembly of an atmospheric pressure chemical free device, and a free device that uses the conversion assembly. [Prior Art] Because Liquid Chromatography-Mass Spectrometer (LC/MS) has the advantages of high sensitivity and good selectivity, it has become the most important instrument for analyzing biological samples in recent years and is widely used. Such as the detection of vitamins, preservatives, pesticides, growth hormones and harmful additives in food; drug metabolism analysis of organisms, screening of diseases and detection of drug content in human body. Liquid chromatography mass spectrometry (LC/MS) mainly combines Liquid Chromatography (LC) with mass spectrometer (MS), and separates the sample to be separated by liquid chromatography. The object is measured and then analyzed by a mass spectrometer. The mass spectrometer mainly includes a free-free device, a mass analyzer and a detector, and depending on the physical and chemical characteristics of the sample, the applicable free device is also different, generally speaking, when the polarity of the analyte is high. Usually, an electrospray ionization (ESI) device is used; and when the test object is a medium or low pole ablation, an atmospheric pressure chemical ionization (APCI) device is used. As shown in the first figure, the free mechanism for the commercial electrospray free device 1 2012 201232598 Schematic 'Electrical sprinkler free device ίο has a nozzle (1) mussel 颂 Wp) u, which has a metal capillary 13 , ~^,ta||(Nebulizer
Gas) 60可自喷頭U仙；金屬毛崎13的管口端i3i對應 質量分析器50之進樣錐51的進樣口 53,杏# A ^ 爾她加向電壓於噴頭 U與質量分析器50的進樣錐Μ時’金屬毛細管。的管口端 ⑶與質量分析器50的進樣口 53之間會形成約侧至麵 伏特的電位差，之後，金屬毛細管13内的待剩樣品溶液川會 受到電場作用力與液體表面張力的影響，形成泰勒錐阳舞 Cone) T ’當電場侧力大於液體表面張力時，就會發生電喷 灑現象，產生帶有電荷的微液滴7卜當微液滴71内的溶劑經 霧化氣體60吹拂而逐漸揮發後，就會形成分析物離子73，之 後經進樣口 53進入質量分析器50内，最終得到質譜圖。 第二圖所不者，為商業化大氣壓化學游離裝置2游離 機制示意圖，大氣壓化學游離裝置2〇具有一金屬管 caPmary)2卜係穿設於一加熱套管(heater)23内金屬管2ι的 管口端211對應質量分析器50的進樣口 53,當金屬管以内的 待測樣品溶液70從管口端211流出時，與金屬管21同軸設置 的一霧化氣體60會分散樣品溶液70,而加熱套管23會使樣品 溶液7G巾的分析減賴氣化為氣態分子，之後透過電源供 應器p將高電壓施予不鏽鋼放電針(corona discharge needle) 8〇 進行電暈放電，使分析物與溶劑的氣態分子游離，再經由質子 轉移(proton transfer)等反應，以形成單電荷分析物離子71，再 進入質量分析器50内，得到質譜圖。 如前所述，由於實際檢測過程中必須針對分析物的結構特 201232598 性選擇適當的游離裝置，以致需要時料換游 ^生且^雜t，導致檢測過程複雜且耗時，徒增檢測二= 性。除此之外，商業化城壓化學游離裝 套管經過長時間使用後，放電針容 料以及加熱 供“袖f —a 电卞谷易積石反而導致離子訊號降 :，而加熱套管也谷跡所以需要時常清洗以及拋光放電 針’使用上較不方便且不易保養。 【發明内容】 有4a於此，本發明之主要目的在於提供一種轉換組件，其 可直接於電喷灑游離裝置的麵，藉以將電喷丨麗游離裝置 轉換為大氣壓化學游離裝置。 本發明之另-目的在於提供—種使用前述轉換組件的游 離裝置僅能夠達成與商業化大氣壓化學雜裝置相近的檢 測結果，且使用較為方便也不需費工保養。 為達成前揭目的，本發明所提供之一種轉換組件，係裝設 於-電嘴_離裝置的噴頭，該噴頭内部穿設有一部分突出於 该喷頭開D端的金屬毛細管，且—霧化氣體可自喷頭開口端喷 出，該電噴灑游離裝置安裝於一質譜儀内，而該質譜儀包括有 一具有一進樣口的質量分析器；前述轉換組件主要包括有一用 以套設於前述噴頭外侧的金屬罩，使該金屬毛細管的一管口端 位於該金屬罩内，以及一同軸地設置於該金屬罩的惰性金屬 絲，其一端位於該霧化氣體的嘴出路經上，I對應前述質量分 析器的進樣Π。藉此，本發明的轉換組件能夠成功地將電喷激 游離裝置轉換為大氣壓化學游離裝置。 201232598 ▲在本發明所提供之轉換組件巾，該金屬罩具有一開口端， 而-亥金屬^的開σ端與該金屬毛細管的管口端係間隔地設 置’並且前述兩者之間的距離範圍較佳為2mm至4mm。 另外’该金屬罩可為一金屬網體、一金屬殼體或其類似物。 在本^明所提供之轉換組件巾，該金屬罩還包括有一組交 人簧片《亥、、且簧片係設置於該金屬罩的内壁面使該組箸片可 ’丨於《亥喷頭的外壁面與該金屬罩的内壁面之間。藉此，透過該 晉片自身的彈性’使該轉換組件能方便且快速地拆裝於該喷 頭。 在本發明所提供之轉換組件中，該惰性金屬絲可為一種選 自始、銀、金、餓、銳、鍊、姥、釕、前述金屬之合金以及不 鏽鋼所構成之族群中的金屬；此外，該惰性金屬絲的外徑範圍 較佳為1〇〇 μη!至15〇 μηι，更且，本發明最佳宜使用外徑1〇〇 的鉑絲。 另一方面’本發明還提供一種使用前述轉換組件的游離裝 置八包括有一内部穿設有一金屬毛細管的喷頭、一套設於該 ，頭卜側的金屬罩、以及—同軸地設置於該金屬罩的惰性金屬 ’、其中該喷頭具有—用以供—霧化氣體喷出的開口端，該 金^毛細f具有—管口端，係突出於該噴顯口端，且可供-，’合液喷灑出’並j_，該金屬毛細管的管口端位於該金屬罩 内而韻性金屬絲的一端位於該霧化氣體的喷出路徑上，並 對應該質#分析!!的進樣σ。藉此，本發明的游離裝置可達成 與商業化大氣魏學游離裝置相近的檢測結果。 有關本發明所提供之轉触件以及_裝置的詳細構造 201232598 堂:下將列舉實施例並配合圖式，在可使本發明領域 ^有通f知識者能_單實施本發明實_的範圍内進行 說明。 【實施方式】 以下簡單說明本發明配合實施例所採用之圖式的内容，其Gas) 60 can be from the nozzle U Xian; the mouth of the metal Maosaki 13 i3i corresponds to the inlet 53 of the sample cone 51 of the mass analyzer 50, apricot # A ^ 尔 her voltage to the nozzle U and mass analysis The injection cone of the device 50 is a 'metal capillary. A potential difference from the side to the surface volt is formed between the nozzle end (3) and the inlet 53 of the mass analyzer 50. Thereafter, the remaining sample solution in the metal capillary 13 is affected by the electric field force and the surface tension of the liquid. , when the electric field side force is greater than the liquid surface tension, an electric spray phenomenon occurs, generating a charged micro-droplet 7 when the solvent in the micro-droplet 71 is atomized by the gas After the 60 is blown and gradually volatilized, the analyte ions 73 are formed, and then enter the mass analyzer 50 through the inlet 53 to finally obtain a mass spectrum. The second figure is a schematic diagram of the free mechanism of the commercial atmospheric pressure chemical free device 2, the atmospheric pressure chemical free device 2 has a metal tube caPmary) 2 is threaded through a heating tube 23 in the metal tube 2 The nozzle end 211 corresponds to the inlet 53 of the mass analyzer 50. When the sample solution 70 to be tested flows out of the nozzle end 211 within the metal tube, an atomizing gas 60 disposed coaxially with the metal tube 21 disperses the sample solution 70. The heating sleeve 23 vaporizes the analysis of the sample solution 7G towel into gaseous molecules, and then applies a high voltage to the corona discharge needle 8 透过 through the power supply p to perform corona discharge. The gaseous molecules of the substance and the solvent are freed, and then reacted by proton transfer or the like to form the singly charged analyte ion 71, and then enter the mass analyzer 50 to obtain a mass spectrum. As mentioned above, since the actual free detection device must select the appropriate free device for the structure of the analyte, so that the need to change the game and the miscellaneous t, resulting in a complex and time-consuming detection process, = sex. In addition, after the commercialization of the commercial pressurization chemical free casing for a long time, the discharge needle material and the heating for the "sleeve f-a electric glutinous grain easy stone cause the ion signal to drop:, and the heating casing also has a trace Therefore, it is necessary to clean and polish the discharge needle from time to time, which is inconvenient and difficult to maintain. [Invention] The main object of the present invention is to provide a conversion assembly which can directly spray the surface of the free device. In order to convert the EFI device to an atmospheric pressure chemical free device. Another object of the present invention is to provide a free device using the foregoing conversion module, which can only achieve a detection result similar to that of a commercial atmospheric pressure chemical device, and In order to achieve the foregoing object, a conversion assembly provided by the present invention is mounted on a nozzle of a device, and a portion of the nozzle is internally provided with a protrusion protruding from the nozzle. a metal capillary at the end, and - the atomizing gas can be ejected from the open end of the nozzle, and the electrospray free device is installed in a mass spectrometer, and the mass spectrometer The utility model comprises a mass analyzer having an inlet; the conversion assembly mainly comprises a metal cover disposed outside the nozzle, such that a nozzle end of the metal capillary is located in the metal cover, and a coaxial arrangement is provided An inert wire of the metal cover, one end of which is located on the nozzle of the atomizing gas, and I corresponds to the injection port of the mass analyzer. Thereby, the conversion assembly of the invention can successfully apply the electrospray device Converted to an atmospheric pressure chemical free device. 201232598 ▲ In the conversion kit of the present invention, the metal cover has an open end, and the open σ end of the -metal is disposed at a distance from the nozzle end of the metal capillary. The distance between the two is preferably from 2 mm to 4 mm. In addition, the metal cover may be a metal mesh body, a metal casing or the like. The conversion cover towel provided in the present invention, the metal cover The utility model further comprises a set of reed reeds, and the reed is disposed on the inner wall surface of the metal cover so that the set of crotch pieces can be disposed on the outer wall surface of the sea nozzle and the inner wall surface of the metal cover. Thereby, the conversion component can be easily and quickly disassembled into the nozzle through the elasticity of the piece itself. In the conversion assembly provided by the invention, the inert wire can be selected from the beginning and the silver. , gold, hungry, sharp, chain, bismuth, bismuth, alloy of the foregoing metal and metal in the group consisting of stainless steel; in addition, the outer diameter of the inert wire preferably ranges from 1 〇〇μη! to 15 〇μηι, Moreover, it is preferable in the present invention to use a platinum wire having an outer diameter of 1 。. On the other hand, the present invention also provides a free device 8 using the foregoing conversion assembly, which comprises a nozzle having a metal capillary inside, and a set. In this case, the metal cover on the head side, and the inert metal disposed coaxially on the metal cover, wherein the shower head has an open end for the atomizing gas to be ejected, and the gold capillary has f- The nozzle end protrudes from the nozzle end and is available for -, 'liquid sprayed out' and j_, the nozzle end of the metal capillary is located in the metal cover and one end of the rhyme wire is located in the mist The gas is ejected on the path and The qualitative analysis # !! injector σ. Thereby, the free device of the present invention can achieve a detection result similar to that of the commercial atmospheric Wei Xue free device. Detailed configuration of the contact member and the device provided by the present invention 201232598: The following examples will be enumerated and the drawings will be used to enable those skilled in the art to practice the invention. Explain inside. [Embodiment] Hereinafter, the contents of the drawings adopted by the present invention in conjunction with the embodiments will be briefly described.
第三圖為一立體圖，顯示依據本發明 轉換組件； 一較佳實施例所為之 第四圖為第三圖的剖視圖； 頭以 第五圖為-示意圖，顯示本發明之轉換組件套設於 及與質量分析器相對位置的態樣； 示本發明之轉換組件套設於喷頭 ’顯示依據本發明另一較佳實施例3 is a perspective view showing a conversion assembly according to the present invention; a fourth embodiment of the preferred embodiment is a cross-sectional view of the third embodiment; the head is shown in a fifth diagram, showing that the conversion assembly of the present invention is sleeved in Aspect of the relative position of the mass analyzer; showing that the conversion assembly of the present invention is sleeved on the showerhead' display according to another preferred embodiment of the present invention
第六圖為一示意圖，顯 後’可能進行的游離機制； 第七圖為一局部剖視圖 所為之游離裝置； 第八圖A至C為質譜圖，肪-iA ^ 、間.、、、頁不本發明實驗例1於負離手 模式的檢測結果； ' 第九圖A至C為質翻’顯示本發明實驗例2於正離子 模式的檢測結果；以及 第十圖A至C為質譜圖，甚自+士&如虫^1 * 口 .、、、貝不本發明實驗例2於負離子 模式的檢測結果。 、 申請人首先在此說明，紅下將要介紹的實施例中，相同 的參考號碼表示相同或類似的元件。 201232598 首先請參照第三圖至第四圖，本發明一較佳實施例所提供 的轉換組件30,主要包括有一金屬罩31以及—惰性金屬絲仏 、該金屬罩3卜於本實施例中概呈方形筒狀，但實際製造時 並不受限於此。 該惰性金屬絲33的材質可選用鉑、銥、金、鐵、鈀、銖、 铑釕、刖述金屬的合金或是不鏽鋼，並且，該惰性金屬絲的 外徑範圍較料⑽㈣至⑼㈣。於本實施例中係選用外徑 為100 μηι的鉑絲。藉此，液相層析儀的動相㈣硫沖咖)液 ，與霧化氣體混合成氣膠粒子(娜Ql)吹拂時，除氣膠粒子可 洗金屬絲之外’該惰性金屬絲可微微振動，使碳粒子不易附 者’減少積碳現象，維持離子訊號n當施加高電壓時， 該惰性金屬絲33能夠產生電暈現象。其次，該惰性金屬絲33 可透過焊接的方式固設於該金屬罩31的外壁面並與該金屬罩 31同轴。 接著，請參閱第五圖，由於該轉換組件30係套設於-電 喷遽游離裝置1G的喷頭1卜因此，為了方便裝卸該轉換組件 3〇，如第三圖與第五圖所示，本發明之轉換組件％的金屬罩 31還可包括有—組交又簧片35，該組交叉簀片35設於該金屬 :的内壁面’ n组簧片35可介於該喷頭u的外壁面與 的内壁面之間，利用簧片35自身的彈性使該轉換 ;:方便且快速地拆裝於該喷頭U。實際應用時，簧片 5的5並無特定關，只要㈣使金料31穩定套設 喷碩11即可，例如亦可使用單一簧片。 實際應用時，如第五圖與第六圖所示，該轉換組件30係 201232598 裝設於該㈣_離裝置ίο㈣⑴丨，㈣電 1〇則安裝於—質譜儀。其中，該質譜儀内包括有-且有_4樣 口 53的質量分析器5G;岐，具有1以供氣 體6〇喷出的開口端111，該噴頭U内部穿設有一金屬毛⑽ 13,且該金屬毛細管13具有—用歸一#、有金屬毛細e 乂 '/、 樣品溶液7〇喷漯出且 突出於該喷頭開口端⑴的管口端⑶。當 於該電喷灑游離裝置10的噴頭UBf，該金_3二二^ 311與該金屬毛細官13的官口端131之間的__ mm至4 mm，於本實施例中約為2爪出。 馬 值得-提的是，於本實施例中還有使用一去 (I^oW-n Gas) 62 ’用以幫助樣品溶液％ 、 該去溶劑氣體62可視實際需求而加以調整。_發仁 接著，如第六圖所示，當施加高電壓於該喷頭n =L31内壁面與㈣11之間的電位差(― 於零亦即’該金屬罩31内部的電場為零，因 崎置10的游離作用，使樣品溶液-不會 游離化，所不的泰勒錐τ ’換言之，樣品溶液7°不會被 游離化，而疋從金屬毛細管13的管口端131 ===倾__2絲㈣，舰仏= 树職輸的惰性 離，再經々放電，使分析物與溶_氣態分子游 同於商業介κ,移等反應，形成帶電荷分析物離子71，，等 化學游離裝置的游離機制。 另方面’依據本發明另一較佳實施例所提供的游離裝置 201232598 二如:金，主要包括有-噴頭91、-穿設於該喷頭 且，可雜κ 93、該金屬罩31以及性金屬絲33，並 91的外壁 ==1透過該簧片35而固設於該喷頭 屬罩31的η ☆ 料31隨於射頭91時，該金 、幵口糕311與該金屬毛細管％ :=佳為2_至4—，該游離裝置心IS 溶劑氣^ = 91喷㈣該霧化氣體6G ’以及可選擇使用該去 =該_91、該金屬毛崎9 金屬絲33以及兮葚Η μ & , 卸平 硪r用性 實施例中的、金屬^細構造、特徵以及功用均與前揭 ”以及二相Π Λ 、金屬罩31、惰性金屬絲 , 相同，因此容申請人在此不再贅述。 ，透過以下實驗例進—步闡明本發明，然而該等實驗例僅 二加瞭解本發明，而非用以限制本發明的範圍，舉凡所 技術領域巾具有通f知識者，在不違反本發明創作精神下所為 的各種變化與修飾均俱屬本發明之範疇。 另外’申請人在此特別說明，在以下實驗例的說明中，電 喷灑游離裝置簡稱為ESI，而大氣壓化學游離裝置簡稱為 APCI。其次’質譜_橫座標為質荷比(m/z)，而縱座標為相 對強度(％)。 <實驗例1> 首先’將具有下列結構式1所示的藥品氟硝西泮 (flunitrazepam，俗稱FM2 ’取自明生生物科技股份有限公司， Mithra Bioindustry Co” Ltd.)溶於乙腈（aeet〇nitrile，純度高於 201232598 95% ’ HPLC 級，購自 j.T.Baker)，配製成濃度 0.14 mg/mL 的 儲備溶液(stock solution)。 檢測時’先將氟硝西泮儲備溶液以50 %(v/v)的乙腈水溶 液分別稀釋成濃度1 pg/mL、5 pg/mL以及1〇 pg/mL的樣品溶 液’以分別供ESI、本發明游離裝置、以及APCI使用。 結構式1The sixth picture is a schematic diagram showing the possible free mechanism; the seventh picture is a partial device for the free device; the eighth picture A to C is the mass spectrum, the fat-iA ^, the interval, the, the page is not The test result of the experimental example 1 of the present invention in the negative off-hand mode; 'the ninth diagrams A to C are the texture turnover' shows the detection result of the experimental example 2 of the present invention in the positive ion mode; and the tenth figure A to C is the mass spectrum, It is the result of the test in the negative ion mode of the experimental example 2 of the present invention. The Applicant first describes here, in the embodiments to be described below, the same reference numerals denote the same or similar elements. 201232598 First, please refer to the third to fourth figures. The conversion assembly 30 according to a preferred embodiment of the present invention mainly includes a metal cover 31 and an inert metal wire, and the metal cover 3 is in the embodiment. It has a square tube shape, but it is not limited to this when it is actually manufactured. The inert wire 33 may be made of platinum, rhodium, gold, iron, palladium, rhodium, iridium, an alloy of the above-mentioned metal or stainless steel, and the outer diameter of the inert wire may be in the range of (10) (4) to (9) (d). In the present embodiment, a platinum wire having an outer diameter of 100 μη is selected. Thereby, the mobile phase of the liquid chromatograph (4) sulfur brewing liquid), when mixed with the atomizing gas to form a gas gel particle (Na Ql), the degassing gel particles can be washed outside the wire, the inert metal wire can be The slight vibration causes the carbon particles to be difficult to attach to reduce the carbon deposition phenomenon, and maintains the ion signal n. When the high voltage is applied, the inert metal wire 33 can generate a corona phenomenon. Next, the inert wire 33 is fixed to the outer wall surface of the metal cover 31 by welding and is coaxial with the metal cover 31. Next, referring to the fifth figure, since the conversion assembly 30 is sleeved on the nozzle 1 of the electrospray eliminator 1G, in order to facilitate the loading and unloading of the conversion assembly 3, as shown in the third and fifth figures. The metal cover 31 of the conversion component % of the present invention may further include a set of intersecting reeds 35 disposed on the inner wall surface of the metal: n group of reeds 35 may be interposed between the nozzles Between the outer wall surface and the inner wall surface, the conversion is made by the elasticity of the reed 35 itself; it is conveniently and quickly attached to the nozzle U. In actual application, the reed 5 5 is not specifically closed, as long as (4) the gold material 31 is stably set to be sprayed, for example, a single reed may be used. In practical applications, as shown in the fifth and sixth figures, the conversion component 30 is installed in the (4) _off device ίο (4) (1) 丨, (4) electricity is installed in the mass spectrometer. Wherein, the mass spectrometer includes a mass analyzer 5G having a _4 sample port 53; 岐, having an open end 111 for discharging gas 6〇, and a metal hair (10) 13 is disposed inside the nozzle U. And the metal capillary 13 has a nozzle end (3) which is squirted with a normal solution, a metal capillary e 乂 ' /, a sample solution 7 突出 and protrudes from the open end (1) of the nozzle. When the nozzle UBf of the electrospray free device 10, the __ mm to 4 mm between the gold _32 221 and the official end 131 of the metal capillary 13 is about 2 in this embodiment. Claw out. It is worth mentioning that in the present embodiment, an I (O^oW-n Gas) 62 ' is used to assist the sample solution %, and the desolvent gas 62 can be adjusted according to actual needs. _Fen, then, as shown in the sixth figure, when a high voltage is applied to the potential difference between the inner wall surface of the nozzle n = L31 and (four) 11 ("zero, that is, the electric field inside the metal cover 31 is zero, Izaki Set the free action of 10, so that the sample solution - will not be free, but the Taylor cone τ 'In other words, the sample solution 7 ° will not be freed, and the enthalpy from the nozzle end of the metal capillary 13 131 === _2 silk (four), the ship 仏 = the inertial separation of the tree, and then the 々 々 discharge, so that the analyte and the dissolved _ gaseous molecules swim with the commercial κ, shift and other reactions, the formation of charged analyte ions 71, and other chemical free The free mechanism of the device according to another preferred embodiment of the present invention. The second embodiment of the present invention provides a free device 201232598, such as gold, which mainly includes a showerhead 91, is disposed on the showerhead, and can be mixed with κ 93. The outer cover of the metal cover 31 and the metal wires 33 and 91 = =1 through the reed 35 and is fixed to the η ☆ material 31 of the head cover 31, and the gold 幵 糕 311 With the metal capillary % := preferably 2_ to 4 -, the free device core IS solvent gas ^ 91 spray (four) the atomizing gas 6G 'and The choice of the use of the = = the _91, the metal Maosaki 9 wire 33 and 兮葚Η μ & , the unloading 硪 r use of the embodiment of the metal structure, features and functions are both before and after And the two-phase Λ 、, the metal cover 31, and the inert metal wire are the same, and therefore the applicant will not repeat them here. The present invention is further clarified by the following experimental examples, but the experimental examples only understand the present invention. Rather than limiting the scope of the invention, it is intended that all such variations and modifications may be made without departing from the spirit of the invention. In the description of the following experimental examples, the electrospray free device is abbreviated as ESI, and the atmospheric pressure chemical free device is abbreviated as APCI. Secondly, the mass spectrum _ cross-symbol is the mass-to-charge ratio (m/z), and the ordinate is the relative intensity. (%) <Experimental Example 1> First, 'flunitrazepam (commonly known as FM2 'taken from Mithra Bioindustry Co Ltd.)) having the following structural formula 1 was dissolved. Acetonitrile Aeet〇nitrile, purity higher than 201232598 95% 'HPLC grade, purchased from jTBaker), formulated into a stock solution with a concentration of 0.14 mg / mL. When testing, 'the first solution of flunitrazepam 50% The (v/v) acetonitrile aqueous solution was diluted to a concentration of 1 pg/mL, 5 pg/mL, and a sample solution of 1 〇pg/mL, respectively, for use in ESI, the free device of the present invention, and APCI. Structural formula 1
H3CH3C
之後’利用具有z-spray之大氣壓游離(API)介面的三段四 極桿質谱儀（購自Waters，型號Quattro Ultima)，搭配ESI、 APCI以及本發明之游離裝置游離並分析該等樣品溶液，各參 數的設定如下：Then, using a three-stage quadrupole mass spectrometer (purchased from Waters, model Quattro Ultima) with a z-spray atmospheric pressure free (API) interface, the sample solutions were freed and analyzed with ESI, APCI, and the free device of the present invention. The parameters are set as follows:
離子源(ion source)溫度：80°C ; 霧化氣體流速：最大； 去溶劑氣體流速：550 L/hr ; 去溫度:ESI與本發明游離裝置正離子模式為 C，ESI與本發明游離裝置負離子模式為働。c，以及紙 正、負離子模式為550。(：；Ion source temperature: 80 ° C; atomization gas flow rate: maximum; solvent removal gas flow rate: 550 L / hr; de-temperature: ESI and the free device of the present invention, the positive ion mode is C, ESI and the free device of the present invention The negative ion mode is 働. c, and paper positive and negative ion mode is 550. (:;
金屬毛細管電壓：ESI正離子模式A 吴武為3.〇 kv，ESI負離+ :式：3.2 kV ’本發明游離裝置正離子模式為2㈣， 發明游離裝置負離子模式為3 2kv; 201232598 放電電流(corona current) : APCI正離子模式為3.2 μΑ，以 及APCI負離子模式為20 μΑ ;以及 質量分析器的進樣錐：ESI為40 V，以及本發明游離敦置 與 APCI 為 35 V。 <實驗例2> 大體上依據與實驗例1相同的方式配製儲備溶液與稀釋儲 備溶液’以獲彳牙樣品溶液以及檢測樣品溶液，除了將具有下列 結構式2所示的藥品非洛地平（fei〇dipine，取自明生生物科技 股份有限公司’ Mithra Bioindustry Co.，Ltd.)溶於甲醇· (methanol ’ HPLC 級’購自 Mallinckrodt Baker, Inc.)，配製成 濃度0.5 mg/mL的儲備溶液(st〇ck s〇iuti〇n)，以及利用50 %(v/v) 的曱醇水溶液稀釋儲備溶液之外。之後，利用與實驗例1相同 的儀器以及參數條件進行樣品溶液的分析。 結構式2Metal capillary voltage: ESI positive ion mode A Wu Wu is 3. 〇kv, ESI negative ion + : formula: 3.2 kV 'The free device positive ion mode of the invention is 2 (four), the invention free device negative ion mode is 3 2kv; 201232598 discharge current ( Corona current): APCI positive ion mode is 3.2 μΑ, and APCI negative ion mode is 20 μΑ; and mass analyzer injection cone: ESI is 40 V, and the free media of the present invention is 35 V for APCI. <Experimental Example 2> The stock solution and the diluted stock solution were prepared in substantially the same manner as in Experimental Example 1 to obtain a dental caries sample solution and a test sample solution, except that the drug felodipine having the following Structural Formula 2 was Fei〇dipine, taken from Mingsheng Biotech Co., Ltd. 'Mithra Bioindustry Co., Ltd.) dissolved in methanol · (methanol 'HPLC grade' available from Mallinckrodt Baker, Inc.), formulated into a reserve of 0.5 mg/mL Solution (st〇ck s〇iuti〇n), and diluting the stock solution with a 50% (v/v) aqueous solution of sterol. Thereafter, the analysis of the sample solution was carried out by the same apparatus and parameter conditions as in Experimental Example 1. Structural formula 2
從第八圖A至C的質譜圖可以發現，雖然ESI、APCI以 及本發明游離裝置的負離子模式檢測，都可以看到[M]·-的訊 號，但是本發明游離装置的訊號強度為1·65χ109(第八圖C)， 與APCI之訊號強度為2.27Χ109 (第八圖Β)相近，而ESI的 訊號強度為9.01X107 (第八圖a)，與APCI以及本發明游離裝 201232598 置的訊號強度相差超過ίο倍。因此可證明將本發明的轉換組 件套設於商業化ESI的喷頭之後，的確能夠成功地將商業化 ESI轉換為大氣壓化學游離的游離機制，且檢測結果與商業化 APCI極為相近。 接著請再參閱第九圖A至C，從ESI的正離子模式可以看 到[M+Na]+的訊號（第九圖A)’但是在本發明游離裝置與Apci 的正離子模式都沒有出現明顯的[M+Na]+訊號，此外，本發明 • 游離裝置之[MH]+的訊號強度為1.59xl08(第九圖C)，與APCI 之[MH]+的訊號強度147408 (第九圖B)相近。再者如第 十圖A至C所示，從ESI的負離子模式只看到的訊號 (第十圖A)，但是在本發明游離裝置與Αρα的負離子模式， 除了出現[M-Η]-的訊號之外’還出現[Μ]·_的訊號，並且，本發 明游離裝置之[Μ]·_的訊號強度為2 96χ丨q8 (第十圖c )與Apci 之[Μ]··的訊號強度（第十圖B)相近。因此可證明將 本發明的轉換組件套設於商業化ESI的喷頭之後，的確能夠成 •功地將商業化ESI轉換為大氣壓化學游離的游離機制，且檢測 結果與商業化APCI極為相近。 纟帛上輯本㈣的轉換崎套設於商#化電嘴濃游 離裝置的喷頭後，即可破壞電喷灑游離裝置的游離機制，並利 用本發明的惰性金屬絲作為放電針進行電暈放電因此能夠成 功並快速地將電噴灑游離裝置轉換為大氣壓化學游離裝置，使 用上較為方便。此外，本發明的游離裝置不僅能夠達成盘商業 =氣壓化料料置相近的檢測結果，时由於作為放電針 、青性金屬絲不易積碳衫需使用加熱套管，因此不需耗時費 201232598 力的進行清洗與拋光的工作，即可維持離子訊號。此外，本發 明有助於在液相層析質譜分析上，減少商業化大氣壓化學游離 裝置的使用需求。 201232598 【圖式簡單說明】 第一圖為一示意圖，顯示商業化電喷灑游離裝置進行的游 離機制； 第二圖為一示意圖，顯示商業化大氣壓化學游離裝置進行 的游離機制； 第三圖為一立體圖，顯示依據本發明一較佳實施例所為之 轉換組件； I 第四圖為第三圖的剖視圖； 第五圖為一示意圖，顯示本發明之轉換組件套設於喷頭以 及與質量分析器相對位置的態樣； 第六圖為一示意圖，顯示本發明之轉換組件套設於喷頭 後，可能進行的游離機制； 第七圖為一局部剖視圖，顯示依據本發明另一較佳實施例 所為之游離裝置； 第八圖A至C為質譜圖，顯示本發明實驗例1於負離子 • 模式的檢測結果； 第九圖A至C為質譜圖，顯示本發明實驗例2於正離子 模式的檢測結果；以及 第十圖A至C為質譜圖，顯示本發明實驗例2於負離子 模式的檢測結果。 15 201232598 【主要元件符號說明】 10電喷灑游離裝置 11 喷頭 111開口端 13 金屬毛細管 131管口端 20 大氣壓化學游離裝置 21金屬管 211 管口端 23加熱套管 30轉換組件 31金屬罩 311 開口端 33惰性金屬絲 35 簧片 50質量分析器 51 進樣錐 53進樣口 60 霧化氣體 62去溶劑氣體 70 樣品溶液 71微液滴 71， 分析物離子 80放電針 90 游離裝置 91喷頭 93 金屬毛細管 931管口端 P電源供應器 T泰勒錐From the mass spectrum of the eighth graph A to C, it can be found that although the signals of [M]·- can be seen in the negative ion mode detection of ESI, APCI and the free device of the present invention, the signal intensity of the free device of the present invention is 1·. 65χ109 (8th C), similar to the signal strength of APCI 2.27Χ109 (8th Β), and the signal intensity of ESI is 9.01X107 (8th a), with APCI and the signal of 201232598 of the present invention The difference in strength is more than ίο times. Therefore, it can be proved that after the conversion assembly of the present invention is placed on the nozzle of the commercial ESI, the commercial ESI can be successfully converted into a free mechanism of atmospheric pressure chemical release, and the detection result is very similar to the commercial APCI. Next, please refer to the ninth diagrams A to C. The signal of [M+Na]+ can be seen from the positive ion mode of ESI (Ninth diagram A). However, neither the free device of the present invention nor the positive ion mode of Apci appears. Obvious [M+Na]+ signal, in addition, the signal intensity of [MH]+ of the free device of the present invention is 1.59xl08 (ninth figure C), and the signal intensity of [MH]+ of APCI is 147408 (ninth figure) B) Similar. Furthermore, as shown in the tenth diagrams A to C, only the signal seen from the negative ion mode of ESI (the tenth figure A), but in the negative ion mode of the free device and Αρα of the present invention, except for the presence of [M-Η]- The signal of [Μ]·_ appears outside the signal, and the signal strength of [Μ]·_ of the free device of the present invention is 2 96χ丨q8 (the tenth figure c) and the signal of [Μ]·· of Apci The intensity (Fig. B) is similar. Therefore, it can be proved that after the conversion assembly of the present invention is placed on the nozzle of the commercial ESI, it is indeed possible to convert the commercial ESI into a free mechanism of atmospheric pressure chemical release, and the detection result is very similar to the commercial APCI. After the conversion of the (4) conversion kit is set in the nozzle of the commercialization nozzle, the free mechanism of the electrospray free device can be destroyed, and the inert metal wire of the invention is used as the discharge needle for electricity. The halo discharge can thus successfully and quickly convert the electrospray free device into an atmospheric pressure chemical free device, which is convenient to use. In addition, the free device of the present invention can not only achieve the detection result of the disk commercial=pneumatic material, but also needs to use the heating sleeve as the discharge needle and the blue wire, so it does not need to be time-consuming 201232598 The cleaning and polishing work of the force can maintain the ion signal. In addition, the present invention facilitates the reduction of the use of commercial atmospheric atmospheric chemical free devices in liquid chromatography mass spectrometry. 201232598 [Simple description of the diagram] The first diagram is a schematic diagram showing the free mechanism of the commercial electrospray free device; the second diagram is a schematic diagram showing the free mechanism of the commercial atmospheric pressure chemical free device; A perspective view showing a conversion assembly according to a preferred embodiment of the present invention; FIG. 4 is a cross-sectional view of the third diagram; and a fifth diagram showing a conversion assembly of the present invention disposed on the nozzle and mass analysis 6 is a schematic view showing a possible free mechanism after the conversion assembly of the present invention is sleeved on the nozzle; FIG. 7 is a partial cross-sectional view showing another preferred embodiment according to the present invention. For example, the free apparatus; the eighth diagrams A to C are mass spectra showing the detection results of the experimental example 1 of the present invention in the negative ion mode; the ninth diagrams A to C are mass spectra showing the experimental example 2 of the present invention in the positive ion mode. The results of the detection; and the tenth graphs A to C are mass spectra showing the results of the detection of the negative ion mode of Experimental Example 2 of the present invention. 15 201232598 [Description of main components] 10 electric spray free device 11 nozzle 111 open end 13 metal capillary 131 nozzle end 20 atmospheric pressure chemical free device 21 metal tube 211 nozzle end 23 heating sleeve 30 conversion assembly 31 metal cover 311 Open end 33 inert wire 35 reed 50 mass analyzer 51 injection cone 53 inlet 60 atomizing gas 62 desolvent gas 70 sample solution 71 microdroplet 71, analyte ion 80 discharge needle 90 free device 91 nozzle 93 metal capillary 931 nozzle end P power supply T Taylor cone