WO1999061905A1 - Appareil hplc permettant de fractionner et de preparer des echantillons pour la spectrometrie rmn et procede de modification de la phase mobile - Google Patents
Appareil hplc permettant de fractionner et de preparer des echantillons pour la spectrometrie rmn et procede de modification de la phase mobile Download PDFInfo
- Publication number
- WO1999061905A1 WO1999061905A1 PCT/JP1999/002783 JP9902783W WO9961905A1 WO 1999061905 A1 WO1999061905 A1 WO 1999061905A1 JP 9902783 W JP9902783 W JP 9902783W WO 9961905 A1 WO9961905 A1 WO 9961905A1
- Authority
- WO
- WIPO (PCT)
- Prior art keywords
- valve
- column
- mobile phase
- heavy
- sample
- Prior art date
Links
- 238000005481 NMR spectroscopy Methods 0.000 title claims abstract description 22
- 238000000034 method Methods 0.000 title claims abstract description 13
- XLYOFNOQVPJJNP-ZSJDYOACSA-N Heavy water Chemical group [2H]O[2H] XLYOFNOQVPJJNP-ZSJDYOACSA-N 0.000 claims abstract description 66
- 239000002904 solvent Substances 0.000 claims abstract description 28
- 238000004128 high performance liquid chromatography Methods 0.000 claims abstract description 23
- XLYOFNOQVPJJNP-UHFFFAOYSA-N water Substances O XLYOFNOQVPJJNP-UHFFFAOYSA-N 0.000 claims abstract description 9
- 239000007788 liquid Substances 0.000 claims abstract description 5
- 238000000926 separation method Methods 0.000 claims description 38
- 238000005070 sampling Methods 0.000 claims description 15
- 150000001875 compounds Chemical class 0.000 claims description 9
- 239000000203 mixture Substances 0.000 claims description 5
- 238000006073 displacement reaction Methods 0.000 claims description 3
- 238000002360 preparation method Methods 0.000 claims description 3
- 238000004587 chromatography analysis Methods 0.000 claims description 2
- 239000012141 concentrate Substances 0.000 claims description 2
- 238000001816 cooling Methods 0.000 claims 1
- 238000010828 elution Methods 0.000 claims 1
- 239000000523 sample Substances 0.000 description 34
- OKKJLVBELUTLKV-UHFFFAOYSA-N Methanol Chemical compound OC OKKJLVBELUTLKV-UHFFFAOYSA-N 0.000 description 30
- 238000002156 mixing Methods 0.000 description 10
- 238000006243 chemical reaction Methods 0.000 description 5
- 238000004458 analytical method Methods 0.000 description 4
- 238000000746 purification Methods 0.000 description 4
- 229910001220 stainless steel Inorganic materials 0.000 description 4
- 239000010935 stainless steel Substances 0.000 description 4
- YZCKVEUIGOORGS-OUBTZVSYSA-N Deuterium Chemical compound [2H] YZCKVEUIGOORGS-OUBTZVSYSA-N 0.000 description 3
- YMWUJEATGCHHMB-UHFFFAOYSA-N Dichloromethane Chemical compound ClCCl YMWUJEATGCHHMB-UHFFFAOYSA-N 0.000 description 3
- 238000001514 detection method Methods 0.000 description 3
- 239000012535 impurity Substances 0.000 description 3
- VLKZOEOYAKHREP-UHFFFAOYSA-N n-Hexane Chemical compound CCCCCC VLKZOEOYAKHREP-UHFFFAOYSA-N 0.000 description 3
- 238000012916 structural analysis Methods 0.000 description 3
- HEDRZPFGACZZDS-UHFFFAOYSA-N Chloroform Chemical compound ClC(Cl)Cl HEDRZPFGACZZDS-UHFFFAOYSA-N 0.000 description 2
- 238000011033 desalting Methods 0.000 description 2
- 229910052805 deuterium Inorganic materials 0.000 description 2
- 125000004435 hydrogen atom Chemical group [H]* 0.000 description 2
- 238000002955 isolation Methods 0.000 description 2
- 238000004949 mass spectrometry Methods 0.000 description 2
- 239000004215 Carbon black (E152) Substances 0.000 description 1
- 239000008186 active pharmaceutical agent Substances 0.000 description 1
- 239000013543 active substance Substances 0.000 description 1
- DNTGGZPQPQTDQF-XBXARRHUSA-N crotamiton Chemical compound C/C=C/C(=O)N(CC)C1=CC=CC=C1C DNTGGZPQPQTDQF-XBXARRHUSA-N 0.000 description 1
- 229960003338 crotamiton Drugs 0.000 description 1
- 238000010612 desalination reaction Methods 0.000 description 1
- 238000010586 diagram Methods 0.000 description 1
- 238000007865 diluting Methods 0.000 description 1
- 238000007599 discharging Methods 0.000 description 1
- 239000003814 drug Substances 0.000 description 1
- 229940088679 drug related substance Drugs 0.000 description 1
- 238000001035 drying Methods 0.000 description 1
- 230000000694 effects Effects 0.000 description 1
- 238000002474 experimental method Methods 0.000 description 1
- 238000000605 extraction Methods 0.000 description 1
- 238000011049 filling Methods 0.000 description 1
- 238000005194 fractionation Methods 0.000 description 1
- 150000008282 halocarbons Chemical class 0.000 description 1
- 229930195733 hydrocarbon Natural products 0.000 description 1
- 150000002430 hydrocarbons Chemical class 0.000 description 1
- 239000004615 ingredient Substances 0.000 description 1
- 238000005342 ion exchange Methods 0.000 description 1
- 238000005259 measurement Methods 0.000 description 1
- 239000000126 substance Substances 0.000 description 1
- 238000006467 substitution reaction Methods 0.000 description 1
Classifications
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/38—Flow patterns
- G01N30/46—Flow patterns using more than one column
- G01N30/468—Flow patterns using more than one column involving switching between different column configurations
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/84—Preparation of the fraction to be distributed
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/84—Preparation of the fraction to be distributed
- G01N2030/8411—Intermediate storage of effluent, including condensation on surface
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/84—Preparation of the fraction to be distributed
- G01N2030/8429—Preparation of the fraction to be distributed adding modificating material
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
- G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
- G01N30/02—Column chromatography
- G01N30/26—Conditioning of the fluid carrier; Flow patterns
- G01N30/28—Control of physical parameters of the fluid carrier
- G01N30/34—Control of physical parameters of the fluid carrier of fluid composition, e.g. gradient
-
- G—PHYSICS
- G01—MEASURING; TESTING
- G01R—MEASURING ELECTRIC VARIABLES; MEASURING MAGNETIC VARIABLES
- G01R33/00—Arrangements or instruments for measuring magnetic variables
- G01R33/20—Arrangements or instruments for measuring magnetic variables involving magnetic resonance
- G01R33/44—Arrangements or instruments for measuring magnetic variables involving magnetic resonance using nuclear magnetic resonance [NMR]
- G01R33/48—NMR imaging systems
- G01R33/4808—Multimodal MR, e.g. MR combined with positron emission tomography [PET], MR combined with ultrasound or MR combined with computed tomography [CT]
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/24—Nuclear magnetic resonance, electron spin resonance or other spin effects or mass spectrometry
-
- Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
- Y10—TECHNICAL SUBJECTS COVERED BY FORMER USPC
- Y10T—TECHNICAL SUBJECTS COVERED BY FORMER US CLASSIFICATION
- Y10T436/00—Chemistry: analytical and immunological testing
- Y10T436/25—Chemistry: analytical and immunological testing including sample preparation
- Y10T436/25375—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.]
- Y10T436/255—Liberation or purification of sample or separation of material from a sample [e.g., filtering, centrifuging, etc.] including use of a solid sorbent, semipermeable membrane, or liquid extraction
Definitions
- HPLC device for sample separation and preparation of NMR measurement and mobile phase conversion method
- the present invention relates to a method and an apparatus for converting a mobile phase in high performance liquid chromatography which can efficiently sample a sample for nuclear magnetic resonance (NMR).
- NMR nuclear magnetic resonance
- HPLC high-performance liquid chromatography
- Japanese Unexamined Patent Publication (Kokai) No. 3-175355 discloses a method and an apparatus for converting a mobile phase in high-performance liquid mass spectrometry. It states that high-performance liquid chromatography captures desired components in a sample and sends the components to a mass spectrometer using a mobile phase suitable for mass spectrometry different from sample separation.
- NMR samples were separated from the original sample several times, but it took a long time to concentrate the sample, and unstable samples were sometimes decomposed during concentration.
- a solvent such as heavy water or heavy methanol, in which a hydrogen atom is replaced by its isotope, deuterium, is used. Since these solvents are very expensive, it is required to prepare measurement samples as efficiently as possible.
- the present invention performs on-line purification, desalination, concentration, and deuteration replacement of trace components in a mixture, and particularly for expensive heavy water and heavy methanol. It is an object of the present invention to provide a system that requires a very small amount of heavy solvent. Disclosure of the invention
- the mobile phase conversion method in high performance liquid chromatography for separating and preparing a sample for NMR measurement of the present invention that achieves the above object is to separate components in the sample by high performance liquid chromatography and perform another transfer. After capturing the components with a phase in a trabbing column, light water is replaced with heavy water, and then the target component is eluted from the trapping column with a heavy solvent other than heavy water.
- the separation and preparation of the desired compound suitable for NMR measurement can be performed simultaneously and efficiently by performing the concentration operation and the conversion of the mobile phase when separating the trace components in the sample by high performance liquid chromatography. I can do it.
- the apparatus of the present invention for carrying out the method of the present invention comprises a separation section for separating components in a sample by high-performance liquid chromatography, a trapping section for capturing components with a trapping column by another mobile phase, and light water by heavy water. It is characterized by comprising a heavy water replacement section to be replaced, and a heavy solvent delivery section that elutes the target component from the trapping column by a heavy solvent other than heavy water.
- the details of the preferred instrument are as follows:
- the separation 'sampling section pumps the mobile phase for sample separation from the pump (P 1), detects the desired compound peak with the detector, passes through the valve (VI) and ends at both ends.
- a loop (LO OP) sandwiched between the valves (V 2) and (V 3) is provided with a means for accumulating the desired compound, and the trapping section controls the mobile phase for sample concentration delivered from the pump (P 2).
- Valve (Vl), valve (V2), loop (LOOP), valve (V3), valve (V4), valve (V5), trapping column (TC), valve (V4) (V3) and valve (V 4) A means for concentrating the desired compound into the trapping column (TC) while mixing the mobile phase for sample concentration via the distribution valve (R) during the
- the pump (P3), valve (V5), trapping column (TC), and valve (V4) are provided in this order to replace light water with heavy water, and the heavy solvent delivery section removes heavy solvents other than heavy water.
- the pump is a liquid sending pump for high-performance liquid chromatography
- the valve is a six-way valve for high-performance chromatography.
- a separation column is a separation column used in ordinary high-performance liquid chromatography, and is not particularly limited to so-called normal-phase columns, reverse-phase columns, GPC columns, and the like.
- a column that can be separated can be selected as appropriate ..:
- a trapping column is a column for capturing and concentrating target components, and is not necessarily a column for high-performance liquid chromatography but a column with a certain pressure resistance. If you can use it.
- the sampling loop is a thin tube for accumulating the components separated from the sample by the separating force ram, and usually uses a stainless steel tube.
- the length is appropriately adjusted depending on the component concentration and the like.
- the heavy solvent means a solvent in which hydrogen atoms in the solvent have been replaced with deuterium (excluding heavy water), and examples thereof include heavy methanol, heavy hydrogen form, heavy methylene chloride and the like. Above all, heavy methanol is widely used.
- the mobile phase used for high-performance liquid chromatography is converted several times.
- the procedure and the like will be specifically described in the following embodiments of the present invention: However, the present invention is not limited to the description. It is not limited and can be changed as appropriate :> Brief description of the drawings
- FIG. 1 is an explanatory diagram showing an example of the device according to the present invention.
- FIG. 2 shows the configuration of the present invention.
- 5 is a chromatogram obtained by the detector D1 and the recorder 1 in the apparatus.
- Figure 3 is a chromatogram obtained by the detector D 2 and the recorder one in the present invention device.
- FIG. 4 is an NMR chart obtained by using the sample for NMR measurement obtained by the apparatus of the present invention.
- Fig. 1 shows a separation / sampling section connected to a pump (P 1) showing a sample concentration and solvent conversion device using high-performance liquid chromatography. Separation
- the sampling section consists of a pump (Pl), injector (1), separation column (PC), detector (Dl), recorder (Dl) connected to a vessel containing the mobile phase for separating the target component. R e and '), as well as hexagonal valves for switching line (V l), the valve (V2, V3), made of loop (lOOP) c
- the drain (DR 1) connected to the six-way valve (VI) is for discharging unnecessary components together with the mobile phase, and these drains (DRA IN) are usually connected by a line made of stainless steel pipe. Have been.
- the line is connected to the sampling loop (LOOP) connected to the switching valve (V2, V3), and the mobile phase is discharged from the drain (DR1).
- LOOP sampling loop
- V2, V3 the switching valve
- a large number of loops are connected to the sampling loop (LOOP).
- the switching valves (V2, V3) By operating the switching valves (V2, V3), the flow path of the mobile phase can be selected to be connected to any loop.
- the components separated in the separation / sampling section are accumulated in different loops for each component.
- the number of loops is set arbitrarily.
- the part connected to the pump (P 2) is the trapping section.
- the trapping section consists of a pump (P2) that delivers a mobile phase of a different composition from the above-mentioned separated mobile phase, a 6-way valve (VI), a valve (V2, V3), and a loop (LOOP) common to the separation and sampling sections.
- P2 pump
- VI 6-way valve
- V2, V3 valve
- LOOP loop
- the trap column uses the same separation mode column as the separation column (PC) so that the target component can be adsorbed, but it is not necessarily a column for high-performance liquid chromatography and it is a column with a certain pressure resistance. If you can use ::
- the column (PC) and column (TC) are used for separation and analysis of various separation modes such as normal phase column, reverse phase column, ion exchange column, affinity column, and GPC column. It is appropriately selected according to the substance to be used.
- the part connected to the pump (P 3) is the heavy water displacement section c
- the heavy water displacement section consists of a pump (P 3) for delivering heavy water, a 6-way valve (V 5) common to the trapping section, a trapping column (TC), a mixing chamber (MG), and a 6-way valve (V 4).
- P 3 a pump for delivering heavy water
- V 5 a 6-way valve common to the trapping section
- TC trapping column
- MG mixing chamber
- V 4 a 6-way valve
- Each bar is usually connected by a stainless steel pipe, and heavy water is discharged from the drain (DR2).
- the section connected to the pump (P4) is the heavy solvent delivery section.
- the mixing chamber is a solvent mixing ram disclosed in Japanese Patent Application Laid-Open No. 5-180820, and a gradient analysis can be easily performed by previously filling a solvent different from the mobile phase into the chamber.
- the in c present invention is a device capable of performing, are useful for further performing further purification and concentration Ri good object component performs separation analysis before taken a sample for NMR min, essential to the present invention Is not a component.
- a method for converting a solvent using the apparatus configured as described above will be described.
- the pump (P1) is operated to transfer the mobile phase for component separation to the line (30), (3 1 ) And inject the sample containing the target component from the injector (I).
- the sample passes through a separation column (PC) together with the mobile phase, and is separated into various components contained in the sample in the column. Each component is separated by a detector (D1) and a recorder (R). ec).
- PC separation column
- D1 detector
- R recorder
- Each of the separated target components passes through the line (32) by switching the six-way valve (VI), and into the sample loop (LOOP) connected at both ends to the switching valves (V2) and (V3). Sent in. Each component is accumulated in a predetermined loop by operating the switching valves (V 2) and (V 3) c
- Switching of the valves (V 2) and (V 3) is performed according to the detection signal of the detector (D 1) so that each component in the sample can be accumulated in a predetermined tube.
- the mobile phase for component separation is discharged from the drain (DR1) through the line (33) and the valve (VI).
- the six-way valve (VI) is switched to connect the lines (34) and (32), and the pump (P2) is connected.
- a mobile phase with a composition different from the mobile phase for component separation hereinafter referred to as “trapping mobile phase” is sent to the sampling loop (LOOP) from the lines (34), (32), and the valve (V2).
- the trap mobile phase is discharged to the drain (DR 2) through the line (39), the mixing chamber (MG), the line (40), and the six-way valve (V4).
- the sub flow path (34 ') is connected to the line (34) and the mobile phase for trapping is mixed with the flow path of the line (34), the trapping column (TC) tends to trap the components.
- the concentration of the mobile phase for separation temporarily increases, It is hard for the ingredients to be troubled.
- the trapping efficiency can be increased by mixing the mobile phase for trap from the sub-flow path and diluting the mobile phase for separation.
- a distribution valve (R) can be installed in the sub flow path to adjust the flow rate.
- the trapping mobile phase serves to trap the target component in the trapping column (TC) and to remove the buffer component used in the separation mobile phase stored in the sampling loop (LOOP).
- the mobile phase for trapping for example, water can be used in a reversed phase system, and a hydrocarbon such as hexane and a halogenated hydrocarbon such as chloroform can be used in a normal phase system.
- a six-way valve (V5) The heavy water is fed into the trapping column (TC) by operating the pump (P3) by switching the line (4 1) and the line (3 8), and the trapping column (TC) and the line (3 8 Replace the mobile phase for traps in (), (39) and (40) with heavy water.
- valves (V4) and (V5) to change the line (43), (40), mixing chamber (MG), line (39), trapping column (TC), line (3 8), Valve (V 5), Line (3 7), (3 6) Valve (V 4), Line (42), Separation column (AC), and Detector (D 2) Turn on the pump (P 4).
- heavy solvents such as heavy methanol (excluding heavy water)
- NMR measurement was performed after fractionation, concentration, and drying.
- the apparatus and method according to the present invention can obtain an NMR measurement sample by continuous online operation, and can use expensive heavy water, heavy methanol, or the like. It was confirmed that an extremely small amount of heavy solvent was required.
- isolation, purification, desalting, concentration, and deuteration substitution of a structural analysis sample can be performed by an online operation, sample dry-up is unnecessary, and it is particularly useful for structural analysis of an unstable sample. is there
- the isolation, purification, desalting, concentration, and deuteration of trace amounts of impurities in biologically active substances that are promising as pharmaceuticals can be performed in a short time.
Landscapes
- General Health & Medical Sciences (AREA)
- Health & Medical Sciences (AREA)
- Life Sciences & Earth Sciences (AREA)
- Chemical & Material Sciences (AREA)
- Analytical Chemistry (AREA)
- Biochemistry (AREA)
- Physics & Mathematics (AREA)
- General Physics & Mathematics (AREA)
- Immunology (AREA)
- Pathology (AREA)
- Treatment Of Liquids With Adsorbents In General (AREA)
- Other Investigation Or Analysis Of Materials By Electrical Means (AREA)
- Sampling And Sample Adjustment (AREA)
Description
Claims
Priority Applications (4)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
DE69942329T DE69942329D1 (de) | 1998-05-26 | 1999-05-26 | Hlpc gerät zur fraktionierung und vorbereitung einer probe für nmr spektrometrie und verfahren zur änderung der mobilen phase |
US09/463,491 US6498040B1 (en) | 1998-05-26 | 1999-05-26 | HPLC apparatus for fractioning and preparing sample for NMR spectrometry and method of changing mobile phase |
EP99922507A EP1001263B1 (en) | 1998-05-26 | 1999-05-26 | Hplc apparatus for fractioning and preparing sample for nmr spectrometry and method of changing mobile phase |
JP55904899A JP3720058B2 (ja) | 1998-05-26 | 1999-05-26 | Nmr測定用試料の分取と調製を行うhplc装置と移動相の変換方法 |
Applications Claiming Priority (2)
Application Number | Priority Date | Filing Date | Title |
---|---|---|---|
JP10/144452 | 1998-05-26 | ||
JP14445298 | 1998-05-26 |
Publications (1)
Publication Number | Publication Date |
---|---|
WO1999061905A1 true WO1999061905A1 (fr) | 1999-12-02 |
Family
ID=15362581
Family Applications (1)
Application Number | Title | Priority Date | Filing Date |
---|---|---|---|
PCT/JP1999/002783 WO1999061905A1 (fr) | 1998-05-26 | 1999-05-26 | Appareil hplc permettant de fractionner et de preparer des echantillons pour la spectrometrie rmn et procede de modification de la phase mobile |
Country Status (5)
Country | Link |
---|---|
US (1) | US6498040B1 (ja) |
EP (1) | EP1001263B1 (ja) |
JP (1) | JP3720058B2 (ja) |
DE (1) | DE69942329D1 (ja) |
WO (1) | WO1999061905A1 (ja) |
Cited By (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE112005002632T5 (de) | 2004-10-26 | 2008-07-17 | Sumitomo Chemical Co., Ltd. | Flüssigchromatograph |
JP2017528707A (ja) * | 2014-08-19 | 2017-09-28 | エレメンタル・サイエンティフィック・インコーポレイテッドElemental Scientific, Inc. | 質量分析のためのシリンジ供給を有する超清浄オートサンプラ |
Families Citing this family (12)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
US6668623B2 (en) * | 2000-03-03 | 2003-12-30 | Mitsubishi Materials Corporation | Method and apparatus for analyzing organic macromolecular component and application thereof |
DE60001177T2 (de) * | 2000-10-25 | 2003-10-23 | Bruker Biospin Gmbh | LC-NMR System, enthaltend eine Vorrichtung zum Einfangen von mindestens einer Komponente eines Chromatographieflusses |
US6402946B1 (en) | 2000-10-26 | 2002-06-11 | Bruker Analytik Gmbh | Device for feeding a chromatography flow |
AU2003208516A1 (en) * | 2002-03-14 | 2003-09-22 | Warner-Lambert Company Llc | Method for characterizing metabolites using hydrogen/deuterium exchange |
JP3816883B2 (ja) * | 2003-03-06 | 2006-08-30 | 株式会社日立ハイテクノロジーズ | 液体クロマトグラフ質量分析装置 |
CA2536809A1 (en) * | 2003-09-05 | 2005-03-17 | Sumitomo Chemical Company, Limited | Liquid chromatographic apparatus |
CN101675329B (zh) * | 2007-09-28 | 2012-04-25 | 株式会社岛津制作所 | 进样装置 |
GB2465956B (en) * | 2007-10-02 | 2012-05-09 | Shimadzu Corp | Preparative separation/ purification system |
US8932468B2 (en) * | 2010-01-12 | 2015-01-13 | The United States Of America As Represented By The Secretary Of The Army | Separation of enzymatically synthesized polyepicatechin via high performance liquid chromatography |
US20170343519A1 (en) * | 2014-12-15 | 2017-11-30 | Shimadzu Corporation | Liquid chromatograph |
US10241013B2 (en) * | 2015-12-08 | 2019-03-26 | Elemental Scientific, Inc. | Inline dilution and autocalibration for ICP-MS speciation analysis |
EP4081795A1 (en) | 2019-12-23 | 2022-11-02 | Waters Technologies Corporation | Sample metering and injection for liquid chromatography |
Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
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JPS55154470U (ja) * | 1979-04-20 | 1980-11-07 | ||
JPH06256227A (ja) * | 1993-03-04 | 1994-09-13 | Japan Energy Corp | 光学活性な化合物の光学分割法及び光学純度測定方法 |
Family Cites Families (1)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
DE4104075C1 (ja) * | 1991-02-11 | 1992-03-19 | Bruker Analytische Messtechnik Gmbh, 7512 Rheinstetten, De |
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1999
- 1999-05-26 WO PCT/JP1999/002783 patent/WO1999061905A1/ja active Application Filing
- 1999-05-26 DE DE69942329T patent/DE69942329D1/de not_active Expired - Lifetime
- 1999-05-26 JP JP55904899A patent/JP3720058B2/ja not_active Expired - Lifetime
- 1999-05-26 US US09/463,491 patent/US6498040B1/en not_active Expired - Lifetime
- 1999-05-26 EP EP99922507A patent/EP1001263B1/en not_active Expired - Lifetime
Patent Citations (2)
Publication number | Priority date | Publication date | Assignee | Title |
---|---|---|---|---|
JPS55154470U (ja) * | 1979-04-20 | 1980-11-07 | ||
JPH06256227A (ja) * | 1993-03-04 | 1994-09-13 | Japan Energy Corp | 光学活性な化合物の光学分割法及び光学純度測定方法 |
Non-Patent Citations (7)
Title |
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"COMPARISON OF ON-LINE AND OFF-LINE LIQUID CHROMATOGRAPHY/NUCLEAR MAGNETIC RESONANCE SPECTROMETRY FOR ANALYSIS OF STEROID MIXTURES.", ANALYTICAL CHEMISTRY, AMERICAN CHEMICAL SOCIETY, vol. 55., 1 January 1983 (1983-01-01), pages 1611 - 1614., XP002922292, ISSN: 0003-2700, DOI: 10.1021/ac00260a040 * |
CLAYTON E., ET AL.: "THE APPLICATION OF HIGH PERFORMANCE LIQUID CHROMATOGRAPHY COUPLED TO NUCLEAR MAGNETIC RESONANCE SPECTROSCOPY AND MASS SPECTROMETRY (HPLC-NMR-MS), TO THE CHARACTERISATION OF IBUPROFEN METABOLITES FROM HUMAN URINE.", CHROMATOGRAPHIA, VIEWEG UND TEUBNER VERLAG, DE, vol. 47., no. 05/06., 1 March 1998 (1998-03-01), DE, pages 264 - 270., XP002922291, ISSN: 0009-5893, DOI: 10.1007/BF02466530 * |
GRIFFITHS L., HORTON R.: "OPTIMIZATION OF LC-NMR III-INCREASED SIGNAL-TO-NOISE RATIO THROUGH COLUMN TRAPPING.", MAGNETIC RESONANCE IN CHEMISTRY., JOHN WILEY, CHICHESTER., GB, vol. 36., 1 January 1998 (1998-01-01), GB, pages 104 - 109., XP002922293, ISSN: 0749-1581, DOI: 10.1002/(SICI)1097-458X(199802)36:2<104::AID-OMR230>3.3.CO;2-6 * |
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YUMI YOKOYAMA, ET AL.: "FUNDAMENTAL PROCESS FOR LC-NMR AND ITS APPLICATIONS", KUROMATOCURAFI - CHROMATOGRAPHY, KUROMATOGURAFI KAGAKKAI, TOKYO, JP, vol. 19, no. 04, 1 January 1998 (1998-01-01), JP, pages 262/263, XP002922290, ISSN: 0917-3048 * |
Cited By (3)
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DE112005002632T5 (de) | 2004-10-26 | 2008-07-17 | Sumitomo Chemical Co., Ltd. | Flüssigchromatograph |
JP2017528707A (ja) * | 2014-08-19 | 2017-09-28 | エレメンタル・サイエンティフィック・インコーポレイテッドElemental Scientific, Inc. | 質量分析のためのシリンジ供給を有する超清浄オートサンプラ |
JP2020101550A (ja) * | 2014-08-19 | 2020-07-02 | エレメンタル・サイエンティフィック・インコーポレイテッドElemental Scientific, Inc. | 質量分析のためのシリンジ供給を有する超清浄オートサンプラ |
Also Published As
Publication number | Publication date |
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EP1001263A4 (en) | 2000-08-23 |
DE69942329D1 (de) | 2010-06-17 |
EP1001263B1 (en) | 2010-05-05 |
JP3720058B2 (ja) | 2005-11-24 |
US6498040B1 (en) | 2002-12-24 |
EP1001263A1 (en) | 2000-05-17 |
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