JP2002372516A - Liquid chromatographic mass spectrometer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To simplify the piping in an LC-MS with other detectors also used therein, and to improve the accuracy in each measurement. SOLUTION: A flow cell 12 is provided in a sample pipe 11 on the proximal side of a nozzle 14 for spraying a sample solution of an atmospheric ionization unit 2A, and an ultraviolet visible light source unit 20 and an ultraviolet visible absorption detection unit 30 of UV 3 are disposed thereacross. An inlet of an evaporation pipe 52 is provided behind an ion transport pipe 17 which attracts ions from an atomizing chamber 13 and feeds them to a mass spectrometer 40, and a laser beam source part 50 and a light scattering detection unit 56 of an ELSD 4 are disposed outside a light incoming window 53 and a light outgoing window 54 formed in the evaporation pipe 52. The UV 3 and the ELSD 4 are integrated with the mass spectrometer, and pipes and/or splitters for mutual connection are omitted thereby.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a liquid chromatograph mass spectrometer, and more particularly, to a liquid chromatograph unit other than a mass spectrometer, such as an ultraviolet-visible spectrophotometer or an evaporative light scattering detector. The present invention relates to a liquid chromatograph mass spectrometer using the above detector in combination.

[0002]

2. Description of the Related Art In recent years, with the great technological progress of mass spectrometers and atmospheric pressure ionizers for ionizing liquid samples, mass spectrometers have been generally used as detectors of liquid chromatographs. .

FIG. 4 is a block diagram showing a basic configuration of a liquid chromatograph mass spectrometer (hereinafter referred to as "LC-MS"). In a liquid chromatograph unit (hereinafter, referred to as “LC”) 1, a liquid sample is introduced into a column along with a flow of a mobile phase, and various sample components contained in the liquid sample are temporally separated, and the column outlet. To reach. The outlet end of the column is connected to the atmospheric pressure ionization section 2A by a pipe, and the sample solution eluted from the column is supplied to the atmospheric pressure ionization section 2A.
At A, it is sequentially ionized by electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), etc., and is sent to the mass spectrometer 2B via an ion transport tube.
The mass analysis unit 2B includes a mass analyzer such as a quadrupole mass filter, and separates and detects given ions according to their mass numbers.

In such an LC-MS, the atmospheric pressure ionization section 2A and the mass analysis section 2B are usually integrated, that is, disposed in the same housing. Hereinafter, it is referred to as “MS”).

[0005] Although MS is an excellent detector that gives useful information on an analyte, not only MS but also a conventional LC detector is required to obtain more information on the analyte. In many cases, multi-detection is performed in combination with an ultraviolet-visible spectrophotometer (hereinafter, referred to as “UV”) or an evaporative light scattering detector (hereinafter, referred to as “ELSD”). When a plurality of such detectors are used together, each detector is connected in series to the LC column outlet, or a sample solution eluted from the column is branched and introduced into each detector in parallel. The configuration is adopted.

FIG. 5 shows an LC using such another detector.
It is a figure which shows the various connection forms of -MS. FIG. 5A shows a configuration in which LC1, UV3, and MS2 are connected in series.
The sample solution eluted from the column of C1 is introduced into UV3,
The sample solution measured in V3 is introduced into MS2 to perform mass spectrometry. FIG. 5 (b) shows MS2 with respect to LC1.
And ELSD4 are connected in parallel. The sample solution eluted from the column of LC1 is branched at an appropriate ratio by a splitter 6 connected to a makeup pump 5, and MS2 is separated.
And ELSD4. Further, FIG.
Is a configuration in which the series connection of FIG. 5A and the parallel connection of FIG. 5B are combined.

[0007]

Since the conventional LC-MS employs the above-described configuration, there are the following various problems. (1) A large installation space is required to arrange a plurality of detectors. (2) The piping connecting the LC and each detector is complicated. As a result, not only is the cost of the piping expensive, but also the proportion of the sample liquid present in the piping is increased (that is, the dead volume is increased), and the detection time of each detector for the same component is shifted (that is, the holding time). Difference) increases. (3) When a splitter is used in a parallel arrangement, it is necessary to adjust a splitting ratio in the splitter. (4) When the makeup solvent is used at the same time as the splitter, the component concentration decreases and the peak intensity decreases. (5) Due to the factor (2) and the influence of the split, the peaks separated by the LC may be diffused, and the skirts of the different peaks may overlap to deteriorate the separation performance. (6) Because the retention time of each detector for the same component is shifted due to the factor (2) or the influence of the split, a process of correcting the time shift is required for accurate identification.

The present invention has been made in order to solve these various problems, and a main object of the present invention is to provide a liquid chromatograph mass spectrometer using other detectors such as UV and ELSD. In addition to simplifying the interconnection of the detectors, the complexity of the connection has led to a shift in the detection time of each detector and a decrease in the analytical accuracy due to the deformation of the peak waveform, and complicated data processing. The object of the present invention is to provide a liquid chromatograph mass spectrometer capable of avoiding the above problem.

[0009]

SUMMARY OF THE INVENTION In order to solve the above-mentioned problems, the present invention provides a method for ionizing a sample liquid eluted from a column of a liquid chromatograph section between a liquid chromatograph section and a mass spectrometric section. A liquid chromatograph mass spectrometer provided with an atmospheric pressure ionization interface provided to a mass spectrometry unit, wherein the atmospheric pressure ionization interface comprises an atomization chamber substantially at atmospheric pressure, and the sample liquid is atomized. A sample pipe for transporting the sample to the chamber, and an ion transport pipe for transporting ions generated in the atomization chamber to the mass spectrometer, a) a flow cell provided in the middle of the sample pipe, An ultraviolet-visible light source section and an ultraviolet-visible absorption detection section, which are arranged with a flow cell interposed therebetween, and an ultraviolet-visible spectrophotometer measuring means, comprising: To the gas flow An evaporating pipe provided with a light entrance window and a light exit window so as to be inserted, a gas suction unit disposed outside the other opening end face of the evaporator pipe, and disposed outside the light entrance window and the light exit window. A laser light source unit and a light scattering detection unit, and an evaporative light scattering detection unit including, and the mass spectrometric unit, the sample solution eluted from the column of the liquid chromatograph unit,
It is characterized in that it is measured by an ultraviolet-visible spectrophotometer and evaporative light scattering detector, respectively.

In the LC-MS according to the present invention, when the sample solution eluted from the column passes through the flow cell, light emitted from the ultraviolet-visible light source is irradiated on the sample solution passing through the flow cell, and the transmitted light Is detected by the ultraviolet-visible absorption detection unit. Thereby, the measurement by the ultraviolet-visible spectrophotometer is achieved. The sample liquid that has passed through the flow cell reaches the atomization chamber immediately thereafter, and is atomized and ionized. Since such ionization can be performed by a conventionally known method, for example, the ESI is configured to include a high voltage application unit that applies a charge to the sample solution, a nebulizing tube that assists atomization, and the APCI includes What is necessary is just to set it as the structure provided with the heating part for solvents, the needle electrode for corona discharge, a nebulize tube, etc. The microdroplets mixed with the ions generated by the atomization are sucked into the evaporating tube by the action of the gas suction unit, and cross the laser light emitted from the laser light source unit and passing through the light incident window while the solvent evaporates further. If the sample component is non-volatile, a cloud of particles is formed by the component, which causes scattering of laser light. The scattered light is taken out of the light exit window and detected by the light scattering detector.
Thereby, the measurement by the evaporative light scattering detecting means is achieved. The inlet end face of the ion transport tube may be arranged at any position before or after the evaporating tube. In any case, ions generated in the atomization chamber are taken into the ion transport tube, sent to the mass spectrometer, and mass spectrometry is achieved as before.

The ultraviolet-visible spectrophotometer and the evaporative light scattering detector may be arranged in the same housing as the mass spectrometer.

[0012]

DESCRIPTION OF THE PREFERRED EMBODIMENTS One embodiment of the present invention will be described below with reference to the drawings. FIG. 2 shows L according to the present embodiment.
FIG. 1 is a block diagram showing the overall configuration of the C-MS, and FIG. 1 is a configuration diagram around an atmospheric pressure ionization unit 2A which is a feature of the present invention. In this example, ESI is used for atmospheric pressure ionization. However, the configuration can be easily changed to APCI as described later.

As shown in FIG. 2, in this LC-MS, UV
The function of the ELSD 4 and the function of the ELSD 4 are substantially integrated into the atmospheric pressure ionization section 2A. These are all housed in the same casing as the mass spectrometer 2B, and LC1 and M
A system is constructed by adding a personal computer as a controller (not shown) to the two devices of S2. Therefore, as before, UV3 and ELS
There is no need to prepare D4 separately, and no complicated piping or splitter is required.

In FIG. 1, a sample solution that is temporally separated and eluted from an LC column is supplied to a sample pipe 11 penetrated by a probe 10. The sample pipe 11 is provided with a flow cell 12 made of quartz glass on its way to the nozzle 14 facing the atomization chamber 13. On both sides of the flow cell 12, a light passage 10 a is formed so as to penetrate to the outside of the probe 10, and an ultraviolet-visible light source unit 20 and an ultraviolet-visible absorption detection unit 30 face each other across the flow cell 12. Are located.

The ultraviolet-visible light source section 20 includes a first light source 21 which is a halogen lamp, a second light source 22 which is a deuterium lamp,
It is configured to include a half mirror 23, a condenser mirror 24, a shutter 25, and the like that mix light emitted from both light sources 21 and 22. The ultraviolet-visible absorption detector 30 includes a reflecting mirror 31, a slit 32, a diffraction grating 33, a photodiode array detector 34, and the like. When the shutter 25 is in the open state, the ultraviolet-visible light source unit 20
The mixed light from 1 and 22 is applied to the flow cell 12. When light passes through the flow cell 12, the light is absorbed at a wavelength specific to the components of the sample solution flowing inside the flow cell. The transmitted light is dispersed in the wavelength direction by the diffraction grating 33, and a plurality of wavelength lights are simultaneously detected by the photodiode array detector 34. Therefore, the photodiode array detector 3
Based on the detection output of No. 4, an absorption spectrum reflecting light absorption by the sample component can be created.

The sample liquid having passed through the flow cell 12 reaches the end of the sample pipe 11 immediately thereafter, and is sprayed from the nozzle 14 into the atomization chamber 13 and ionized. More specifically, a voltage of several kV is applied to the tip of the sample pipe 11 through which the sample liquid flows by the thin metal tube 15 to generate a strong uneven electric field near the nozzle 14. The sample liquid is separated into electric charges by this electric field, and is atomized with a biased electric charge with the help of a nebulizing gas (such as nitrogen gas) through the nebulizing tube 16. The droplets generated thereby collide with surrounding atmospheric components and are miniaturized, and the solvent in the droplets evaporates to generate gas ions. The generated ions pass through the ion transport tube 17 through the entrance opening of the ion transport tube 17 located in front of it.
It is drawn inside and sent to the mass spectrometer 40. The ion transport tube 17 is a heated capillary that is appropriately heated, and further promotes the vaporization of the solvent from the drawn fine droplets to promote ionization.

Since the inlet opening of the ion transport pipe 17 is located off the center axis of the spray of the nozzle 14, fine droplets and ions which are often present around the jet from the nozzle 14 can be efficiently removed. Entrapment and entrapment of large droplets that are often present in the center of the jet can be avoided.

The ions sent to the mass analyzer 40 through the ion transport tube 17 are converged and accelerated by the ion lens 41 and sent to the quadrupole mass filter 42, where the ions have a specific mass number (mass m / charge z). ) Passes through the quadrupole mass filter 42 and reaches the detector 43 where it is detected. In the mass spectrometer 40, a quadrupole mass filter 42
A mass spectrum can be created by appropriately scanning the voltage applied to and changing the passage conditions of ions.

In front of the jet from the nozzle 14, an evaporating tube 5 is provided.
There are two inlet openings, and an aspirator depressurized drain 55 is provided outside the other opening of the evaporation tube 52. The aspirator decompression drain 55 sucks the liquid droplets in the atomization chamber 13 into the evaporating tube 52 by a high-speed gas flow. The evaporating tube 52 is heated to an appropriate temperature to further promote the volatilization of the solvent contained in the droplet. A light entrance window 53 and a light exit window 54 are provided at appropriate positions on the side peripheral surface of the evaporation tube 52. A laser light source unit 50 including a laser light source 51 is arranged outside the light incident window 53, and irradiates a laser beam so as to be substantially orthogonal to a gas flowing inside the evaporating tube 52. Also, the light exit window 5
A light scattering detection unit 56 including a photodetector such as a photomultiplier tube 57 is disposed outside the photomultiplier tube 57.

When the liquid droplets jumping into the evaporating tube 52 are only a highly volatile solvent, the laser light passes through the solvent vapor, so that the scattering of light is very small and the light intensity of the scattered light is almost constant. become. On the other hand, if a non-volatile component is present in the droplet, a cloud of fine particles due to this component is generated in the evaporating tube 52, and when the particle cloud is irradiated with laser light, light scattering occurs. The light exit window 54 is provided at a position where the scattered light passes, and the light scattering detection unit 56 detects the light intensity of the scattered light. The detection signal has a value that depends on the concentration of the component, the particle size distribution, and the like.

In the above configuration, the sample liquid measured by the ultraviolet-visible spectrophotometric measuring means comprising the ultraviolet-visible light source section 20 and the ultraviolet-visible absorption detecting section 30 is sprayed from the nozzle 14 into the atomization chamber 13 almost without delay. Further, after the ions (including fine droplets) generated thereby are introduced into the ion transport tube 17, the remaining droplets are introduced into the evaporation tube 52 almost without delay, and the laser light source unit 50, the evaporation tube 52, and the light scattering. Detector 5
6 is measured by the evaporative light scattering detecting means. Therefore, UV3, mass spectrometer 2B, ELS in FIG.
The three measurements of D4 will be made in very close time.

FIG. 3 is a schematic diagram showing a peak waveform of a certain component obtained by the above three kinds of measurements.
5B is an example of the measurement according to the present invention, and FIG. 5B is an example of the measurement according to the conventional configuration shown in FIG. As shown in FIG. 3B, in the conventional configuration, since it takes time for the sample liquid to flow inside the pipe connecting the UV3, the ELSD4, and the MS2, the peak generation time for the same component, that is, A large deviation occurs in the holding time. In addition, such a time lag varies depending on the flow rate of the LC1 column and the flow rate of the makeup solvent. ELSD4 and M
The peak intensity at S2 changes depending on the split ratio at the splitter 6 and the flow rate of the makeup solvent, and errors tend to occur in the quantitative analysis. On the other hand, in the method according to the present invention, as shown in FIG. 3A, the deviation of the retention time of the same component in UV3, MS2, and ELSD4 can be shortened, and all can be shortened to 3 seconds or less. Also, MS2
And ELSD4, the peak intensity is improved, and since no makeup solvent is used, the peak diffusion is small and a sharp peak shape appears. As described above, according to the present invention, the deviation of the holding time of each detector with respect to the same component is small, and the deformation of the peak shape is small.

In the above embodiment, the mass spectrometer 40
The inlet of the ion transport tube 17 for introducing ions into the evaporator is provided before the inlet opening of the evaporator tube 52.
Provided behind the exit opening of
2 may be performed prior to the measurement.

In the above embodiment, ESI is used as the atmospheric pressure ionization method. However, other atmospheric pressure ionization methods such as APCI can be used. That is, in the configuration shown in FIG.
The probe 10 including a unique structure is configured to be detachable from the atomization chamber 13, and a probe dedicated to APCI is mounted when ionization by APCI is performed. In this APCI-dedicated probe, for example, the front of a nozzle for spraying a sample liquid is surrounded by a heater, and further, a needle electrode for corona discharge is disposed in front of the heater. The droplets ejected from the nozzle with the help of the nebulizing gas are immediately heated by the heater to evaporate the solvent, and the small droplets are chemically reacted with carrier gas ions (buffer ions) generated by corona discharge from the needle electrode to ionize. Do. This gives E
As in the case of SI, the sample solution immediately after measurement by the ultraviolet-visible spectrophotometer can be ionized and taken into the mass spectrometer 2B. When the APCI and the ESI are compared, the former is higher in temperature of the droplets in the atomization chamber 13 than the latter, so that the desolvation can be performed more efficiently. Therefore, in the latter case, it is desirable to set the temperature higher in order to further promote the evaporation of the solvent inside the evaporation tube 52.

Further, it is apparent that the above-described embodiment is merely an example of the present invention, and that changes and modifications other than those described above can be appropriately made within the spirit of the present invention.

[0026]

As described above, the liquid chromatograph mass spectrometer according to the present invention has the following various effects. (1) UV and ELSD functions are integrated into the mass spectrometer, so even if you want to perform multi-detection,
Since it is only necessary to connect the eluate of the LC column to the inlet of the mass spectrometer as in the conventional case, the piping is greatly simplified, and a splitter and a makeup pump are not required. Therefore, the labor for piping can be greatly reduced, and the cost for these pipings and the like can be reduced. (2) It is not necessary to prepare UV and ELSD separately.
The installation space may be narrow. (3) Since the detectors are arranged very close to each other and the dead volume in the pipe becomes very small, the difference in detection time (difference in holding time) between the detectors becomes very small. Therefore, the process of correcting such a shift in the holding time becomes unnecessary, or even if the correction process is required, the dependency on the column flow rate or the like is reduced, so that the correction process is facilitated. (4) The peak intensity in MS and ELSD is increased, and the spread of the peak can be suppressed. Therefore, the separation performance of a plurality of components is improved, and the accuracy of both quantitative analysis and qualitative analysis is improved as compared with the conventional case. As described above, according to the liquid chromatograph mass spectrometer of the present invention, not only the cost can be reduced and labor can be saved, but also the analysis performance can be improved.

[Brief description of the drawings]

FIG. 1 is a configuration diagram around an atmospheric pressure ionization unit, which is a feature of one embodiment of the liquid chromatograph mass spectrometer of the present invention.

FIG. 2 is a block diagram showing the overall configuration of the LC-MS according to the embodiment.

3A and 3B are schematic diagrams showing a peak waveform of a certain component obtained by UV, MS, and ELSD. FIG. 3A shows an example of measurement according to the present invention, and FIG. 3B shows a conventional configuration shown in FIG. An example of measurement.

FIG. 4 is a block diagram showing a basic configuration of a liquid chromatograph mass spectrometer.

FIG. 5: L in combination with other detectors (UV, ELSD)
The figure which shows the various connection forms of C-MS.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... LC2 ... MS2A ... Atmospheric-pressure ionization part 10 ... Probe 10a ... Light passage 11 ... Sample line 12 ... Flow cell 13 ... Atomization chamber 14 ... Nozzle 15 ... Metal thin tube 16 ... Nebulize tube 17 ... Ion transport tube 2B 40, mass spectrometry unit 41, ion lens 42, quadrupole mass filter 43, detector 3, UV 20, ultraviolet-visible light source unit 21, first light source 22, second light source 23, half mirror 24, condenser mirror 25 ... Shutter 30 ... Ultraviolet-visible absorption detector 31 ... Reflector 32 ... Slit 33 ... Diffraction grating 34 ... Photodiode array detector 4 ... ELSD 50 ... Laser light source unit 51 ... Laser light source 52 ... Evaporation tube 53 ... Light entrance window 54 ... Light emission window 55 Aspirator decompression drain 56 Light scattering detector 57 Photomultiplier tube

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) G01N 30/74 G01N 30/74 EZ 30/78 30/78

Claims (2)

[Claims] 1. A liquid chromatograph mass having an atmospheric pressure ionization interface between a liquid chromatograph section and a mass spectrometry section, the sample liquid eluted from a column of the liquid chromatograph section being ionized and supplied to the mass spectrometry section. An analyzer, wherein the atmospheric pressure ionization interface includes an atomization chamber substantially under atmospheric pressure, a sample pipe for transporting the sample liquid to the atomization chamber, and an ion generated in the atomization chamber. An ion transport tube for transporting to the mass spectrometry unit, a) a flow cell provided in the middle of the sample conduit, and an ultraviolet-visible light source unit and an ultraviolet-visible absorption detection unit arranged with the flow cell interposed therebetween. And b) an opening end face in the atomization chamber, and a light entrance window and a light exit window provided so as to intersect the flow of gas sucked from the atomization chamber. Evaporator tube and the evaporator A gas suction unit disposed outside the other open end surface of the tube, a laser light source unit and a light scattering detection unit disposed outside the light entrance window and the light exit window, and evaporative light scattering detection means including: Wherein the sample liquid eluted from the column of the liquid chromatograph section is measured by the mass spectrometer, the ultraviolet-visible spectrophotometer, and the evaporative light scattering detector, respectively. Analysis equipment. 2. The liquid chromatograph mass spectrometer according to claim 1, wherein the ultraviolet-visible spectrophotometer and the evaporative light scattering detector are arranged in the same housing as the mass spectrometer. apparatus.