JPH0943202A - Liquid chromatograph mass spectrometer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To optimize a flow rate of a nebulizing gas for nebulizing a specimen in an LC/MS. SOLUTION: A specimen component separated by a column 7 is nebulized to a nozzle at a needle tip of a probe 14 by means of a nebulizing gas supplied from a nebulizing gas supply pipe 17 connected to the probe and is ionized by being brought into contact with a buffer ion created by a discharge electrode 16. A flow rate controlling valve 19 is controlled by a computer 20 such that the flow rate of the nebulizing gas is optimized corresponding to a kind of the specimen component eluting from the column 7.

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 (hereinafter referred to as LC) using an atmospheric pressure ionization method.
/ MS), and more particularly LC / MS using atmospheric pressure ionization.

[0002]

2. Description of the Related Art LC / MS has the characteristics that it is possible to analyze heat-stable, non-volatile substances without chemical modification, and to perform qualitative analysis for each component at the same time. Widely applied. LC with such features
In / MS, since the components separated by the liquid chromatograph are ionized and introduced into the mass spectrometer, an interface for ionizing the separated components is required. Interfaces commonly used for LC / MS include electrospray ionization (ESI), atmospheric pressure chemical ionization (A
There is an atmospheric pressure ionization (API) interface for PCI, etc.

Here, in the ESI method, the eluent from the liquid chromatograph is introduced into a capillary (electrospray probe) to which a high voltage is applied, and fine droplets having more charges than the tip are sprayed under atmospheric pressure. It evaporates the solvent and vaporizes solute ions directly. Note that nebulizing gas is used in order to cope with stable atomization of fine droplets and high flow rate.

On the other hand, the APCI method is a nebulizer (atomizer).
At, the eluent from the liquid chromatograph is forcibly sprayed by the gas flow and the droplet is desolvated by heating it, and then the sample is ionized (chemical ionization) by the buffer ions generated by the corona discharge. It is a thing. The ESI method is a method suitable for highly polar ions, while the APCI method is a method suitable for medium-polarity and low-polarity ions, so that both have complementary surfaces.

FIG. 3 shows a typical configuration of an interface for performing ionization by the APCI method. In the figure, 31
Is a liquid chromatograph, 32 is an interface, and 33 is a mass spectrometer. The interface 32 has a probe 34 having a thin tube through which a sample component passes and has a needle-shaped tip, a heater 35 provided so as to surround the needle portion of the probe 34, and a discharge electrode attached to the front surface of the opening of the probe 34. Attach an atmospheric pressure chemical ionization unit comprising 36. A heating pipe 37 (heating mechanism not shown) is provided at a position facing the probe 34.
Is installed.

The probe 34 is heated by the heater 35, and a voltage of several KV is applied to the discharge electrode 36. By setting in this way, the eluent separated and sent in the column 38 of the liquid chromatograph 31 is a nozzle at the tip of the needle of the probe 34 due to the nebulizing gas from the gas line separately connected to the probe 34. And is desolvated by the heater 35, and then ionized by contact with buffer ions generated in the discharge electrode. The ionized eluent is further heated by the heating pipe 37 to evaporate the solvent component and drawn into the mass spectrometer 33.

[0007]

However, in the conventional LC / MS interface, the flow rate of the nebulizing gas for atomizing the sample is fixed and cannot be changed during the analysis. Generally, the optimum value of the gas flow rate differs depending on the composition of the mobile phase of the liquid chromatograph used and the sample component.With the conventional fixed flow rate method, nebulizing gas is not sufficient depending on the sample component,
I couldn't spray enough. This adversely affects the ionization at a later stage, resulting in a decrease in ionization efficiency and a decrease in analytical sensitivity.

Therefore, it is an object of the present invention to provide an LC / MS having a nebulizing gas flow rate that is optimum for the composition of the eluent from the liquid chromatograph (sample components, mobile phase composition).

[0009]

In order to solve the above-mentioned problems, the present invention comprises a nebulizer for spraying a nebulizing gas to an eluent from a liquid chromatograph, and after the forced spraying in the nebulizer, elution under atmospheric pressure is carried out. In LCMS for ionizing liquid, a flow control valve is provided in the nebulizer,
A control unit for controlling the flow rate of the control valve according to the composition of the eluent from the liquid chromatograph and the elution time is provided.

Here, atmospheric pressure ionization means electrospray ionization (ESI) and atmospheric pressure chemical ionization (ASI).
PCI), etc., including all those that are ionized under atmospheric pressure. This atmospheric pressure ionization is performed by an interface that connects the liquid chromatograph and the mass spectrometer. This interface must be provided with at least an ionization unit for ionizing sample components and a heating mechanism for desolvation.
The ionization unit can apply a high voltage of about several kV in the case of ESI and an electrospray probe that also serves as a nebulizer, and in the case of APCI, a nebulizer for atomizing a sample, a probe for spraying, a discharge for ionization. It is necessary to have at least an electrode. Further, the heating mechanism corresponds to, for example, a heating pipe arranged at a position facing the probe of the ionization section. A metal pipe having high thermal conductivity is used as the material of the pipe.

The nebulizer sprays a nebulizing gas to forcibly spray the eluent from the liquid chromatograph, and nitrogen is usually used as the nebulizing gas, but an inert gas such as argon or helium is also used. The nebulizer is provided with a nebulizing gas source and a flow control valve. As the flow rate control valve, for example, an electronic flow controller used in a semiconductor manufacturing apparatus, a gas chromatograph or the like can be used.

[0012] The controller controls the nebulizer to have an optimum flow rate according to the elution time (retention time) of the sample components from the liquid chromatograph or the composition of the mobile phase when performing gradient analysis with the liquid chromatograph. To control. The control is performed by a time program, for example, since the retention time is known in advance and the optimum flow rates of the sample components are stored.

[0013]

BEST MODE FOR CARRYING OUT THE INVENTION Embodiments of the present invention will be described below with reference to the drawings. FIG. 1 is an LC showing an embodiment of the present invention.
It is a block diagram which shows / MS. FIG. 1 is a diagram showing a general configuration of an LC / MS. 1 is a liquid chromatograph, 2 is an interface, 3 is a mass spectrometer, the liquid chromatograph 1 is composed of a mobile phase reservoir 4, a sample introduction part 5, a liquid feed pump 6 and a separation column 7, and the mass spectrometer 3 is Converging lens 8 that converges ionized sample molecules, quadrupole 9 that sorts the converged ions according to the type of charge, electron multiplier tube (not shown) provided after quadrupole 9, and ion The rotary pump 10 and the turbo molecular pump 11 keep the passage system of the vacuum state.

Further, the interface 2 has an atmospheric pressure chemical ionization section 12 using the APCI method and a heating pipe 13. The atmospheric pressure chemical ionization unit 12 has a probe 14 having a thin tube through which a sample component passes and has a needle-shaped tip, a heater 15 provided so as to surround the needle portion of the probe 14, and attached to the front surface of the opening of the probe 14. The discharge electrode 16 is provided.

A nebulizing gas supply pipe 17 is connected to the probe 14. The nebulizing gas supply pipe 17 is located inside the probe 14 so as to cover the pipe from the separation column 7, and by supplying the nebulizing gas into the probe 14, the eluent from the liquid chromatograph is forcibly sprayed. To be done.

The probe 14 of the atmospheric pressure chemical ionization section 12
Are fixed by the fixing member 21. The fixing member 21 has a fixed position with respect to the heating pipe 13, and in this figure, a housing shared with the mass spectrometer 3 is used as the fixing member 21. The heating pipe 13 is heated by a heater (not shown), and the heating pipe 13 and the needle tip of the probe 14 are arranged as close as possible so that more sample components enter the heating pipe 13. The sample components are heated in the heating pipe 13 to evaporate the solvent, and only the ions of the sample are extracted from the heating pipe 13 and sent to the mass spectrometer 3.

A nebulizing gas source 18 is connected to the nebulizing gas supply pipe 17, and a flow control valve 19 is arranged in the nebulizing gas supply pipe 17. The flow rate control valve 19 is an electronic flow controller, and the valve is automatically opened and closed (pressure control is performed) according to a flow rate program set in the computer 20 to adjust the flow rate.

Next, the flow rate program set in the computer 20 is shown in FIG. FIG. 2A shows a chromatogram of the sample separated by the separation column 7 of the liquid chromatograph 1. The peak of this chromatogram shows each sample component, and the optimum flow rate suitable for that component is shown in FIG. 2 (b). The flow control valve 19 is controlled by the computer 20 according to the program of FIG. The flow rate program is not limited to that shown in FIG. 2. For example, in the case of gradient analysis, the flow rate program may be controlled according to the composition of the mobile phase instead of being adjusted according to the sample components.

When the LC / MS as described above is used for analysis, it is carried out as follows. First, liquid chromatograph 1
The mobile phase is sent by the liquid sending pump 6 of 1. and the separation column 7 is kept in a steady state. In this state, the sample is introduced from the sample introduction unit 5, and the separation column 7 separates each sample component. The separated sample is sprayed on the nozzle at the needle tip of the probe 14 by the nebulizing gas from the nebulizing gas supply pipe 17 connected to the probe 14, desolvated by the heater 15, and then generated on the discharge electrode 16. Is ionized by contact with buffer ions that are generated. The flow rate of the nebulizing gas is changed according to the program shown in FIG.

The ionized sample component is further heated by the heating pipe 13 to evaporate the solvent component and drawn into the mass spectrometer 3. The ions drawn into the mass spectrometer 3 are converged by a converging lens 8, separated by a quadrupole 9, and detected by an electron multiplier (not shown).

In the above description, the flow rate of the nebulizing gas is controlled in accordance with the program shown in FIG. 2 (b) in the computer 20, but the present invention is not limited to this, and the separation column 7 and the interface are controlled. A normal detector (for example, a UV detector) or the like may be provided between the two to monitor the peak and control according to the peak.

[0022]

INDUSTRIAL APPLICABILITY In the LC / MS of the present invention, the nebulizing gas flow rate can be set in accordance with the type of sample components and the mobile phase composition of gradient analysis. It will be possible.

[Brief description of drawings]

FIG. 1 is a configuration diagram of an LC / MS that is an embodiment of the present invention.

FIG. 2 is a diagram showing a flow program of a nebulizing gas according to the present invention.

FIG. 3 is a block diagram of a conventional liquid chromatograph mass spectrometer (APCI method).

[Explanation of Codes] 1: Liquid chromatograph 2: Interface 3: Mass spectrometer 12: Atmospheric pressure chemical ionization unit 13: Heating pipe 14: Probe 16: Discharge electrode 17: Nebulizing gas supply pipe 18: Nebulizing gas source 19 : Flow control valve 20: Computer

Claims (1)

[Claims] 1. A liquid chromatograph mass spectrometer, comprising a nebulizer for spraying a nebulizing gas to an eluent from a liquid chromatograph, and ionizing the eluent under atmospheric pressure after forced nebulization by the nebulizer, comprising: A liquid chromatograph mass spectrometer, comprising: a flow rate control valve; and a control unit for controlling the flow rate of the control valve according to the composition and elution time of the eluent from the liquid chromatograph.