JP4945770B2 - Liquid chromatographic analysis method and apparatus - Google Patents

Description

  The present invention relates to a liquid chromatograph analysis method and an analysis apparatus for performing desalting between a liquid chromatograph and various analysis means or fractionation means.

  Liquid chromatography (LC) can separate various mixtures without being limited by sample volatility and thermal stability. This liquid chromatography is integrated with detection means such as various spectrometers for detecting and identifying the separated substance, and is effective as an analytical means such as liquid chromatography-mass spectrometry (LC-MS). Demonstrate.

  In such liquid chromatography, conventionally, separation conditions using a non-volatile buffer such as phosphate as a mobile phase have been widely used. In particular, phosphate has buffer capacity in a wide pH range, so it is easy to study the separation conditions, and since it has no absorption in the ultraviolet / visible wavelength range, the background level of the chromatogram is low. Has been universal.

  However, these salts have the following disadvantages in analysis or fractionation. That is, when a mass spectrometer capable of obtaining substance information with high sensitivity is used as a detection means, a decrease in ionization efficiency due to the presence of salts and contamination of the ion source are major problems. In addition, even when the eluate from the liquid chromatograph is fractionated and the solvent is removed, and measurement is performed by NMR, IR, etc., a large amount of salts contained in the eluate may become an obstacle and obtain an accurate spectrum. There is a problem that you can not.

Conventionally, the following techniques are known as techniques for removing nonvolatile salts from the mobile phase of a liquid chromatograph.
The first is a technique using a two-dimensional liquid chromatograph, which uses a system in which a flow path switching valve, a sample loop, and a trap column are arranged between two reversed-phase liquid chromatographs (Patent Literature). 1, see FIG. That is, the mobile phase solvent containing the non-volatile buffer solution is sent from the pump a, and the sample injected from the injector b is separated by the column c of the first-dimensional reversed-phase liquid chromatograph and attached to the switching valve d. A plurality of sample loops (not shown) are collected in several segments. The sample component solution stored in the sample loop is expelled from the pump f with a solvent not containing a non-volatile buffer mainly composed of water, trapped in the trap column e, and the non-volatile salts contained in the solution are washed away. Next, the solvent composition of the liquid fed from the pump f is changed (gradient) to water / acetonitrile and the like, and the sample components trapped in the trap column are eluted, and the second-phase reversed-phase liquid chromatograph is used. The sample components are re-separated by introduction into the column g and introduced into the mass spectrometer.

  The second is a technique using an ion suppressor of an ion chromatograph apparatus (Patent Document 2). In an analysis using an ion chromatograph, an ion suppressor may be used in order to reduce the background derived from the eluent when using an electric conductivity detector. This uses electrolysis of the eluent and an ion exchange membrane, and can change the non-volatile salt used as the eluent to water. This suppressor can be used as a non-volatile buffer for the reverse phase partition chromatograph. It is applied to liquid removal.

  However, in the former, it is necessary to once hold the sample component in the trap column during the desalting operation. That is, since continuous desalting cannot be performed, an eluate using a phosphate buffer cannot be directly introduced into a mass spectrometer, and mass spectrometry data cannot be obtained on the same time axis as a liquid chromatogram. . In the first-dimensional chromatographic separation, it is difficult to hold the sample component eluted from the octadecylsilylated silica gel (ODS) column under the eluent condition with a large proportion of the organic solvent in the trap column. Another problem is that mobile phase conditions (ratio of organic solvent) that can be used in the first-dimensional chromatographic separation are limited.

  In the latter case, there is a problem that usable eluent is limited. That is, the eluent used in ion chromatography is basically a non-volatile buffer in an aqueous solution, and no organic solvent is used. Therefore, the ion exchange membrane used in the suppressor has low organic solvent resistance. On the other hand, many organic solvents such as acetonitrile, methanol, ethanol, and acetone are used in reverse phase partition chromatography used in most LC-MS. Therefore, using this suppressor for LC-MS has a great limitation on eluent conditions.

Special Table 2004-53694 JP-A-6-194357

  The present invention relates to providing a liquid chromatographic analysis method and an analysis apparatus that can be continuously and easily desalted without changing the separation conditions of liquid chromatography and can be detected by various detection devices in a flow state. .

That is, the present invention relates to the following 1) to 7).
1) A liquid chromatograph that uses a liquid chromatograph analyzer having at least a liquid chromatograph part, a desalting part, and a detection / analysis part to elute an analysis sample with a mobile phase solvent containing a non-volatile salt, and then performs detection. In the analysis method, a desalting treatment is performed by bringing a functional particle having non-volatile salt adsorption ability into contact with a mobile phase solvent containing the eluted analysis sample and separating the non-volatile salt from the mobile phase solvent, and then the analysis sample. For detecting liquid chromatograph.
2) The desalting treatment is arranged between the liquid chromatograph part and the detection / analysis part, and separates and collects the liquid introduction part, the liquid-liquid separation part for realizing multiphase laminar flow, and each layer. The liquid chromatographic analysis method according to 1) above, which is performed by a microchannel device including a separation / recovery unit.
3) The liquid chromatographic analysis method according to 1) or 2) above, wherein the functional particles are magnetic substance-containing particles.
4) The liquid chromatograph analysis method according to any one of 1) to 3) above, wherein the detection of the analysis sample is mass spectrometry.
5) In a liquid chromatograph analyzer comprising at least a liquid chromatograph part, a desalting part, and a detection / analysis part, the desalting part is disposed between the liquid chromatograph part and the detection / analysis part, and a non-volatile salt adsorption capacity A liquid chromatograph analysis device comprising a means for separating a non-volatile salt from a mobile phase solvent using functional particles having the above.
6) Micro comprising a means for separating a non-volatile salt from a mobile phase solvent, a liquid introduction part, a liquid-liquid separation part for realizing a multiphase laminar flow, and a separation / recovery part for separating and collecting each layer The liquid chromatograph analyzer according to 5), which is a flow channel device.
7) The liquid chromatograph analyzer according to 5) or 6) above, wherein the detection / analysis means of the detection / analysis unit is a mass spectrometer.

According to the present invention, the non-volatile salt contained in the eluate of the liquid chromatograph can be desalted in the flow state after elution. Therefore, a spectrometer such as a mass spectrometer can be connected online without changing the huge amount of separation condition assets in a liquid chromatograph, and the target substance can be easily obtained by fraction collection, so that it can be efficiently separated over a wide range. Identification is possible.
Thereby, the problem that the mass spectrometer or the like cannot be selected as the detector of the liquid chromatograph because the nonvolatile buffer cannot be used is solved, and the application range of the liquid chromatograph can be expanded.

Schematic diagram of a conventional liquid chromatograph analyzer Schematic configuration diagram of the liquid chromatograph analyzer of the present invention Flow path configuration diagram of desalination section Cross-sectional view of the liquid-liquid separation section Cross-sectional view of a device with a temperature control mechanism Flow path configuration diagram of desalination section Flow path configuration diagram of desalination section Flow path configuration diagram of desalination section Flow path configuration diagram of desalination section Flow path configuration diagram of desalination section

The liquid chromatographic analysis method of the present invention uses a liquid chromatographic analyzer having at least a liquid chromatograph section, a desalting section, and a detection / analysis section to elute an analysis sample with a mobile phase solvent containing a nonvolatile salt. Then, in a liquid chromatographic analysis method in which detection is performed, by contacting a functional particle having a non-volatile salt adsorption ability with a mobile phase solvent containing an eluted analysis sample, the non-volatile salt is separated from the mobile phase solvent. The sample is desalted and then the analysis sample is detected.
FIG. 2 shows a schematic configuration diagram of an analyzer for carrying out the liquid chromatographic analysis method of the present invention.

  The liquid chromatograph in the liquid chromatograph section may be of any type as long as it is a variety of chromatographs using a solvent containing various non-volatile salts as a mobile phase. For example, reverse phase liquid chromatograph, ion exchange chromatograph And ion-pair chromatographs.

  As the mobile phase solvent containing various non-volatile salts, known ones used in the various chromatographs described above can be used. For example, a buffer comprising phosphoric acid, perchloric acid, alkylsulfonic acid and / or a salt thereof. Solution, or a mixed solution of the buffer solution and an organic solvent such as methanol, ethanol, acetonitrile, acetone, tetrahydrofuran and the like.

Examples of detection of the sample in the detection / analysis unit include measurement by mass spectrometry. The mass spectrometer is most suitable as an apparatus connected to the liquid chromatograph analyzer of the present invention because its sensitivity is very high and it can be measured with a very small amount of sample.
In addition, the target substance can be easily obtained from the eluate subjected to the desalting treatment according to the present invention by fractionation and solvent removal, and these can be measured by detection means such as NMR and IR. Is also possible.

  The desalting treatment is performed on the eluate eluted by the liquid chromatograph, and includes a means for separating the non-volatile salt from the mobile phase solvent using functional particles having a non-volatile salt adsorption ability. Done by the department. The mobile phase solvent containing the analysis sample eluted from the liquid chromatograph is introduced into the desalting apparatus, desalted, and then sent directly to the analyzing apparatus.

  Functional particles include particles capable of adsorbing non-volatile salts, such as silica fine particles such as silica gel, zirconia, and synthetic polymers that have a hydrophobic functional group such as octadecyl group and can adsorb non-volatile salts on their pores and surfaces. Examples thereof include particles and magnetic substance-containing particles containing titania, silica gel, hydroxyapatite, zirconia and the like that can adsorb magnetic particles such as iron oxide, nickel oxide, and cobalt oxide and nonvolatile salts.

  As a means for separating the non-volatile salt from the mobile phase solvent using functional particles having non-volatile salt adsorption ability, specifically, liquid introduction for introducing the mobile phase solvent that has passed through the liquid chromatograph section A micro-channel device including a liquid-liquid separation unit for realizing a multiphase laminar flow, a magnetic recovery unit for recovering magnetic substance-containing particles, and a separation / recovery unit for separating and recovering each layer Used.

A microchannel device is a three-dimensional structure for performing extraction, separation, purification, and the like of a trace substance, which includes a microchannel that is a microspace.
The micro flow path has only to be a passage having a micrometer size width, height and diameter and capable of flowing a liquid. For example, the width, depth and diameter are about 20 to 1,000 μm, respectively. It is sufficient that the width is 100 to 300 μm, the height is 50 to 150 μm, and the diameter is 100 to 500 μm. The length of the flow path in the liquid-liquid separation unit is preferably adjusted as appropriate according to the amount of liquid introduced.

The microchannel device of the present invention can be created by, for example, joining two substrates, upper and lower or left and right, each having a groove serving as a channel, and the channel has a groove provided on the bonding surface of both substrates. Formed by joining. Here, the material of the upper and lower substrates or the left and right substrates to be joined may be the same, or different materials may be freely combined.
Further, when a temperature control mechanism (temperature sensitive liquid-liquid separator mechanism) described later is provided, a heat insulating sheet made of Teflon (registered trademark) or the like can be sandwiched between the substrates.

  Examples of the material of the substrate include metals such as stainless steel, hastelloy, titanium, aluminum and brass; synthetic resins such as Teflon (registered trademark), Daiflon and PEEK, borosilicate glass, soda lime glass, aluminoborosilicate glass and quartz glass. However, it is preferable to use a metal from the viewpoint of high thermal conductivity, durability and chemical resistance, and more preferable to use stainless steel because it is applied to a liquid chromatograph. .

FIG. 3 shows a basic flow path configuration diagram of a micro flow path device when hydrophobic fine particles are used as functional particles. Hereinafter, this will be described as an example.
Reference numeral 1 denotes a liquid introduction hole for introducing a mobile phase solvent containing a sample component from a liquid chromatograph, into which a mobile phase solvent containing a nonvolatile salt such as a phosphate is introduced. On the other hand, 2 is a liquid introduction hole for introducing a solution in which functional particles adsorbing the nonvolatile salt contained in the mobile phase solvent are dispersed.

  The flow path from the liquid introduction holes 1 and 2 is a Y-shaped flow path, and both liquids are mixed by the Y-shaped mixing part 3, and the non-volatile salt in a mobile phase is adsorb | sucked by a functional particle. In addition, the adsorption of the non-volatile salt to the functional particles is performed by installing a high-mixing mixer or the like that can uniformly mix the mobile phase solvent and the functional particle dispersion before introduction into the microchannel. Alternatively, the two liquids may be mixed and then introduced into the flow path (FIGS. 7 and 10).

4 is a liquid introduction hole for introducing a nonpolar solvent such as cyclohexane. The nonpolar solvent introduced from 4 merges with the liquid mixed in the mixing unit 3 in the Y-shaped mixing unit 5, and a two-layer flow is formed in the liquid-liquid separation unit.
The nonpolar solvent used here may be any solvent that can form a two-layer flow with the mobile phase solvent, and in addition to cyclohexane, for example, hexane, ethyl acetate, benzene, toluene, chloroform, dichloromethane, or the like can be used. .

  An edge for stably separating the liquid-liquid interface can be appropriately provided on the inner surface of the flow path of the liquid-liquid separation unit. For example, it is possible to provide edges (7a, 8a) having a structure that gradually increases in length from upstream to downstream (6 to 8) (FIG. 4). Such a structure makes it possible to achieve both sufficient liquid-liquid contact time and stable liquid-liquid separation.

Further, in the liquid-liquid separation part, in order to facilitate the realization of a two-phase laminar flow, the temperature distribution in the flow path cross-sectional direction perpendicular to the flow direction is described in Japanese Patent Application No. 2009-19950. A temperature control mechanism (temperature sensitive liquid-liquid separator mechanism) can be provided (FIG. 5).
For example, when the laminar flow is formed up and down with respect to the flow direction, the temperature distribution is at the upper and lower portions of the flow channel, and when the laminar flow is formed at the left and right with respect to the flow direction, the left portion of the flow channel. The upper lower part or the left part of the left part is divided into a high temperature side (for example, 30 to 50 ° C.) and a low temperature side (for example, 10 to 30 ° C.), respectively.
The temperature difference between the high temperature side and the low temperature side varies depending on the type and combination of liquids used, but is preferably 10 ° C. or higher, more preferably 10 to 25 ° C., and more preferably 15 to 25 ° C. .

The temperature control is performed by, for example, providing a heating medium on the high temperature side and a cooling medium on the low temperature side. Specifically, when forming a laminar flow in the vertical direction of the cross section of the flow path, Is formed in the right and left direction of the channel cross section, a heating medium and a cooling medium may be provided on each of the left and right bases. Examples of the heating medium include a rod heater, a seat heater, and a Peltier module.
Examples of the cooling medium include a refrigerant introduction device and a Peltier module.
Such a temperature control medium may be installed either on the inside or on the surface of the substrate according to its function, or a plurality of sites may be installed. For example, it is also possible to arrange two temperature control media in series with respect to the flow direction of the flow path, and perform switching only on the downstream side or both control, and by performing such control, a wide range of liquids It is possible to cope with the amount of introduction. In addition, by performing heating and cooling according to the flow rate of the liquid to be introduced, it is possible to perform liquid-liquid separation in a desired flow rate range, for example, 1 to 200 μL / min.

  The entire device is preferably covered with a heat insulating material so that the temperature distribution is not easily affected by the outside air temperature.

In each of the liquid-liquid separated layers, the mobile phase solvent containing the sample component from which the non-volatile salt has been removed is separated by the separation / recovery unit downstream of the flow path and introduced into the detection / analysis unit.
The separation of each layer may be performed by branching the flow path up and down when forming a laminar flow vertically with respect to the flow direction, and branching left and right when forming a laminar flow left and right with respect to the flow direction. .

  When hydrophobic fine particles are used as the functional particles, the particles adsorbing the non-volatile salt move to the nonpolar solvent layer due to the surface hydrophobicity, and therefore the mobile phase containing the sample component from which the non-volatile salt has been removed The solvent is introduced into the detection / analysis unit.

When magnetic substance-containing particles are used as the functional particles, the movable magnet 18 is disposed in the vicinity of the flow path before the separation / recovery unit, and the magnetic substance-containing particles are attracted to the nonpolar solvent side in the flow path. After that, the nonpolar solvent layer and the mobile phase solvent are separated at the downstream Y-shaped branch point, and the mobile phase solvent including the sample component from which the non-volatile salt has been removed is introduced into the detection / analysis unit (see FIG. 8-10).
The movable magnet 18 is composed of a drive shaft (18a) and a belt-like magnet (18b), and is driven along the flow path from upstream to downstream of the flow path. Therefore, the magnetic substance-containing particles also move along the flow path wall surface from upstream to downstream in accordance with the movement of the magnet.

  Hereinafter, the present invention will be specifically described by way of examples. However, the present invention is not limited to these examples.

Example 1
FIG. 6 shows a desalting interface in which hydrophobic fine particles are used as functional particles and provided with a temperature sensitive liquid-liquid separator mechanism.
A mobile phase solvent containing a sample component and a non-volatile salt such as a phosphate is introduced into the liquid introduction hole 1. On the other hand, the hydrophobic fine particles for adsorbing the non-volatile salt are introduced from the liquid introduction hole 2 by being dispersed in a solvent such as water. Both are mixed in the Y-shaped mixing part 3, and the non-volatile salt is adsorbed by the hydrophobic fine particles. Further, a liquid introduction hole 4 for introducing a nonpolar solvent such as cyclohexane is provided downstream. The nonpolar solvent is introduced from the liquid introduction hole 4 and joined with the mobile phase solvent in the Y-shaped mixture 5. 14 is provided with the temperature sensitive liquid-liquid separator mechanism shown in FIG. That is, a seat heater is installed on the surface of the upper block 13a of the flow path to increase the temperature, and a Peltier cooler is installed on the lower side of the lower block 13b to reduce the temperature, and the temperature difference between them is controlled to 10 ° C. or more. . Thereby, a two-layer flow is easily formed. Furthermore, edges (7a, 8a) that gradually increase in length from 6 to 8 are provided in the downstream flow path (see FIG. 4) to stabilize the liquid-liquid interface.
The hydrophobic fine particles adsorbing the non-volatile salt move to the non-polar solvent layer due to its surface hydrophobicity, and the non-polar solvent layer is separated from the mobile phase solvent layer at the downstream Y-shaped branch point. A mobile phase solvent layer containing the sample component from which is removed is introduced into the detection / analysis section.

Example 3
FIG. 7 shows a configuration of a desalting interface device in which hydrophobic fine particles are used as functional particles, and a mixer with high mixing efficiency is installed outside.
A mobile phase solvent containing a sample component and a non-volatile salt such as a phosphate is introduced into the liquid introduction hole 15 of the mixer section. On the other hand, the hydrophobic fine particles for adsorbing the non-volatile salt are dispersed in a solvent such as water and introduced from the liquid introduction hole 16 of the mixer section. Both are mixed in the mixer, and the mixed liquid containing the hydrophobic fine particles adsorbing the nonvolatile salt is discharged from the outlet of the mixer and introduced into the liquid introduction hole 17 of the interface device. The aqueous solvent in which the hydrophobic fine particles for adsorbing the non-volatile salt are dispersed is again introduced from the liquid introduction hole 2 of the device. Both are remixed in the Y-shaped mixing part 3, and the remaining phosphate is adsorbed on the hydrophobic fine particles.
A nonpolar solvent such as cyclohexane is introduced from the liquid introduction hole 4 and joined with the liquid from the upstream in the Y-shaped mixing section 7. In the flow path downstream from the mixing section 5, there are provided edges (the length is gradually increased from 6 to 8) for separating the liquid-liquid interface at points 6, 7, and 8 (see FIG. 4) a two-layer flow is formed. The hydrophobic fine particles adsorbing the nonvolatile salts move to the nonpolar solvent layer due to their surface hydrophobicity. The nonpolar solvent layer is separated from the mobile phase solvent layer at the Y-shaped branch point downstream of the flow path, and the mobile phase solvent layer containing the sample component from which the nonvolatile salts have been removed is introduced into the detection / analysis unit.

Example 4
FIG. 8 shows a configuration of a desalting interface device in the case of using magnetic substance-containing particles as functional particles.
A mobile phase solvent containing a sample component and a non-volatile salt such as a phosphate is introduced into the liquid introduction hole 1. On the other hand, the magnetic substance-containing particles for adsorbing the non-volatile salt are introduced from the liquid introduction hole 2 after being dispersed in a solvent such as water. Further, a liquid introduction hole 4 for introducing a nonpolar solvent such as cyclohexane is provided downstream. The nonpolar solvent is introduced from the liquid introduction hole 4 and joined with the mobile phase solvent in the Y-shaped mixture 5. An edge that gradually increases in length from 6 to 8 is provided in the flow path downstream from the mixing section 5 to separate the liquid-liquid interface (see FIG. 4), and a two-layer flow is formed. Is done.
A movable magnet 18 composed of a drive shaft (18a) and a belt-like magnet (18b) is disposed in the vicinity of the flow path downstream of the flow path. Magnetic substance-containing particles adsorbing non-volatile salts are attracted by magnetic force in the flow path near the magnet and move from the mobile phase solvent to the nonpolar solvent layer, and the nonpolar solvent at the downstream Y-branch point The mobile phase solvent layer containing the sample components separated into the layer and the mobile phase solvent layer and from which the non-volatile salts have been removed is introduced into the detection / analysis unit. By disposing the movable magnet so that the edge structure is downstream from the tip position of the movable magnet, it is possible to prevent the phase shift of the magnetic substance-containing particles.

  FIG. 9 shows a case where magnetic substance-containing particles are used as functional particles (an example in which magnetic substance-containing particles are dispersed in a nonpolar solvent), and a temperature-sensitive liquid-liquid separator mechanism is provided in the same manner as in Example 1. FIG. 10 shows a configuration example of a desalting interface device, and FIG. 10 shows a case where magnetic substance-containing particles are used as functional particles, and a desalting interface device in which a mixer with high mixing efficiency is installed outside in the same manner as in Example 2. A configuration example of was shown.

a pump b injector c column d switching valve e trap column f pump g column 1 liquid (mobile phase solvent) introduction hole 2 liquid (functional particle) introduction hole 4 liquid (nonpolar solvent) introduction hole 3, 5 mixing section 6 to 8 edge forming part (7a and 8a edge)
9 channel 10 heat insulation sheet 11 sheet heater 12 Peltier cooler 13a upper block 13b lower block 14 temperature sensitive liquid-liquid separator mechanism 15 liquid (mobile phase solvent) introduction hole 16 liquid (functional particle) introduction hole 17 liquid (mobile phase) Solvent-functional particles) Introduction hole 18 Movable magnet

Claims (8)

A liquid chromatographic analysis method in which an analysis sample is eluted with a mobile phase solvent containing a non-volatile salt and then detected using a liquid chromatographic analyzer having at least a liquid chromatograph part, a desalting part, and a detection / analysis part In this method, the desiccant treatment is performed by contacting the functional particles having the ability to adsorb non-volatile salt with the mobile phase solvent containing the eluted analytical sample to separate the non-volatile salt from the mobile phase solvent, and then detecting the analytical sample. A liquid chromatographic analysis method characterized in that a desalting treatment is arranged between a liquid chromatograph part and a detection / analysis part, and a first liquid introduction hole for introducing a mobile phase solvent; liquid introduction portion having a second liquid inlet for introduction of the solution obtained by dispersing functional particles having a nonvolatile salt adsorption ability to disperse the mobile phase solvent and the functional particle Liquid for realizing the multi-phase laminar flow mixing liquid - liquid separation unit and the line power sale liquid chromatograph analysis by the micro-channel device having a separation and recovery section to separate and recover each layer. Liquid chromatography analysis of claim 1, wherein the functional particle is a magnetic material-containing particles. The liquid chromatographic analysis method according to claim 1 or 2 , wherein the analysis sample is detected by mass spectrometry. In a liquid chromatograph analyzing device having at least a liquid chromatograph part, a desalting part, and a detection / analysis part, the desalting part is disposed between the liquid chromatograph part and the detection / analysis part and has a non-volatile salt adsorption ability. from the mobile phase solvent using functional particles in a liquid chromatograph analyzer and characterized in that it comprises a means for separating the non-volatile salt, a means for separating the non-volatile salt from the mobile phase solvent, moving A liquid introduction part having a first liquid introduction hole for introducing a phase solvent and a second liquid introduction hole for introducing a solution in which functional particles having nonvolatile salt adsorption ability are dispersed; and the mobile phase solvent. Oh Ru in microchannel device comprising a liquid separation section and the separation and recovery section for separating and recovering each layer - liquid for realizing the functional particles are mixed with a solution prepared by dispersing the multiphase layer flow and liquid body click Romatograph analyzer. The liquid chromatograph analyzer according to claim 4, further comprising a third liquid guide hole for introducing a nonpolar solvent as the liquid introduction part. 6. The liquid chromatograph analyzer according to claim 4, wherein the functional particles are magnetic substance-containing particles. The liquid chromatograph according to claim 6, wherein a magnet is disposed in the vicinity of the flow path before the separation / recovery unit. The liquid chromatograph analyzer according to any one of claims 4 to 7, wherein the detection / analysis means of the detection / analysis unit is a mass spectrometer.

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