JP2002116193A - Liquid chromatographic mass spectrographmeter - Google Patents

Abstract

[PROBLEMS] To optimize the flow rate of a sample introduced into a mass spectrometer after separating and purifying chemical substances. A liquid chromatograph mass spectrometer provided with a column for separating and purifying a chemical substance from a solution containing a mobile phase and a sample, and a mass spectrometer for analyzing each component of a separated and purified eluent, When the eluent from 1 is introduced into the analyzer 7 via the splitter 3, a UV detector 2 for detecting the concentration of the separated and purified component is provided, and the UV detector 2 is transferred from the splitter 3 to the analyzer 7 according to the concentration. Is varied.

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 optimization of an eluent supplied to an analyzer.

[0002]

2. Description of the Related Art Liquid chromatograph mass spectrometers include, for example, a combination of a high-speed purification system (HTPA) for combinatorial chemistry and a liquid chromatograph mass spectrometer. HTPA which performs separation and purification performs separation and purification by flowing a large volume of mobile phase (10 to 30 ml / min). However, a liquid chromatograph mass spectrometer (LC / MS) for analyzing purified components requires a high vacuum to obtain a mass spectrum from sample ions, and can flow only a small amount (1 ml / min). . For this reason, a splitter is provided between the separation device and the mass spectrometer, and a sample is introduced at a constant split ratio.

On the other hand, in order to increase the ionization efficiency of the mass spectrometer, when the sample components separated by the column are sprayed with a nebulizing gas and supplied to the mass spectrometer, the gas flow rate depends on the type of the sample components. There is a proposal to optimize by using the method (Japanese Patent Laid-Open No. 9-43202).

[0004]

In the case of a combined apparatus in which a separation device and an analyzer are combined, the flow rate of the mobile phase is 1 ml / ml.
min is the limit. As described above, in the case of flowing a large-volume mobile phase in combination with HTPA, if the concentration of the separated and purified component is too high, the isotope peak ratio on the mass spectrum may not match or a large amount of sample ions may be generated. Normal peaks may not be obtained due to saturation of peaks or chemical ion reaction. On the other hand, if the concentration after splitting is too low, there is a problem that the sample ions disappear and the mass spectrum cannot be detected. In addition, since a large amount of sample molecules flow into the path as contamination, time is required for maintenance.

[0005] In the above-mentioned Japanese Patent Laid-Open Publication, the gas flow rate of the nebulizer is controlled in accordance with the composition and elution time of the eluent from the column. For this purpose, the elution time of the components must be known in advance. However, it is not possible to control a sample whose elution time is unknown.

SUMMARY OF THE INVENTION In view of the above-mentioned problems of the prior art, an object of the present invention is to optimize the amount of a solution introduced into a mass spectrometer and obtain a stable ionization of a sample and an accurate spectrum at all times. It is to provide a liquid chromatograph mass spectrometer.

[0007]

SUMMARY OF THE INVENTION In order to achieve the above object, the present invention provides a separation apparatus (column) for separating and purifying a chemical substance from a solution containing a mobile phase and a sample, and analyzing each component of the separated solution. In a liquid chromatograph mass spectrometer equipped with a mass spectrometer, when the solution from the separation device is introduced into the spectrometer via a splitter, the concentration of the component separated and purified after the separation device is detected. A concentration detector is provided, the split ratio of the splitter is changed according to the detected concentration, and the amount of liquid sent from the splitter to the mass spectrometer is varied. According to this, it is possible to have a programming function for always performing analysis under optimum conditions from a high concentration to a low concentration sample.

Further, a system for replenishing the amount of the solvent is provided between the splitter and the mass spectrometer, and the amount of the solution is varied according to the concentration or the amount of the liquid to be sent. According to this, the amount of the solvent for promoting ionization is optimized.

[0009]

DESCRIPTION OF THE PREFERRED EMBODIMENTS A liquid chromatograph mass spectrometer according to one embodiment of the present invention will be described below with reference to the drawings.

FIG. 1 is a system configuration diagram of a liquid chromatograph mass spectrometer. This system is configured as a combined device of HTPA and liquid chromatograph. A sample of a chemical or a chemical product is injected into an eluent (here, methanol and water) called a mobile phase, and separated by a column 1 as a separation device. In time, the solution separated for each component is UV
(Ultraviolet) The concentration of each component is detected by the detector 2, and the concentration is divided by the splitter 3 into what is dispensed by the fraction collector 4 and what is introduced into the mass spectrometer (MS) 7.

The analysis result of the mass spectrometer 7 is detected by the data processing device 8 as a mass spectrum. The fraction collector 4 dispense based on the result of the mass spectrometer 7. The solvent replenishment pump 6 feeds the solvent in the solvent tank 5 to the solution from the splitter 3.

As described above, in the combined separation / analysis apparatus of this embodiment, after the synthesized chemicals and chemical products are separated and purified, qualitative analysis is performed to find out what the respective components are, and the fractionation is performed. Check that the components were synthesized as estimated. In the case of the HTPA-liquid chromatograph composite device, a large amount of synthesized sample is separated and purified for each component using a large amount of mobile phase solvent, and the mass spectrometer 7 ionizes each component (sample molecule). Qualitative and quantitative analyzes are performed by dispersing the mass of the ions in mass. For this reason, the inside of the apparatus is evacuated to a high vacuum so that the sample ions do not collide with molecules floating in the apparatus and disappear.

In this embodiment, the structure is such that the split ratio of the splitter 3 can be changed. FIG. 2 shows an example of the structure of the splitter. As shown, the solution from the column 1 is divided into a fraction collector 4 and a mass spectrometer 7. At this time, the splitter ratio is changed by moving the valve 31 in and out. Usually, the flow rate of the separated solution from the column 1 is 10 to 30 (ml / min), and the flow rate introduced into the mass spectrometer 7 is 1/100 to 1 (ml / min). The change of the split ratio by the valve 31 is performed according to the concentration of the concentration detector 2.

FIG. 3 shows the component concentration and the mass spectrum. (A) is a component concentration, which shows a UV signal intensity. In the figure, the signal intensity of peak 2 is greatly reduced with respect to the signal intensity of peak 1. (B) is a mass spectrum when the split ratio is constant, and shows a peak 1 and a peak 2 respectively. In the case of the peak 2, it is difficult to distinguish it from the noise component. (C) shows MS7 for peak 2
7 is a mass spectrum when the amount of sample introduced into the sample is increased to 10 times that in the case of (b). Peak 2 is more than doubled. On the other hand, since there is no change in the noise component, identification is easy.

FIG. 4 shows an example of a split program (relationship between valve opening and signal strength). UV2 signal strength is 0
２０００2000 (mv), whereas the valve opening (split ratio) on the MS7 side changes from 1/10 to 1/1000.

The data processing device 8 programs this relationship in advance and controls the valve 31 of the splitter 3 so as to change the splitter ratio in accordance with the concentration detected by the UV detector 2.

In this embodiment, the amount of the solvent sent by the pump 6 is also changed according to the signal intensity from the UV detector 2 or the splitter ratio. The amount of liquid sent from the pump 6 is set to MS7
In order to optimize the total flow introduced into
(Ml / min).

Thus, when the signal intensity from the UV detector 2 is low, the amount of sample introduced into the MS 7 is increased.
When the signal intensity from the UV detector 2 is high, M
The amount of sample introduced into S7 is reduced, and analysis is always performed under optimal conditions. Furthermore, since the total flow rate to the MS 7 is optimized (here, a fixed amount), ionization is promoted and the problem of contamination is solved.

[0019]

According to the present invention, a liquid chromatograph mass spectrometer that handles a large amount of samples can optimally adjust the amount of sample introduced into the mass spectrometer, so that accurate mass spectrometry can be performed.

[Brief description of the drawings]

FIG. 1 is a system configuration diagram of a liquid chromatograph mass spectrometer according to one embodiment of the present invention.

FIG. 2 is a structural diagram showing an example of a splitter.

FIG. 3 is a graph showing a component concentration by a UV detector and a mass spectrum by a mass spectrometer.

FIG. 4 is a graph showing a relationship between a valve opening and a signal intensity (an example of a split program).

[Explanation of symbols]

DESCRIPTION OF SYMBOLS 1 ... Column, 2 ... UV detector, 3 ... Splitter, 4 ... Fraction collector, 6 ... Pump, 7 ... Mass spectrometer (M
S), 8: Data processing device.

Claims (4)

[Claims] 1. A liquid chromatograph mass spectrometer comprising: a separation device for separating and purifying a chemical substance from a solution containing a mobile phase and a sample; and a mass spectrometer for analyzing each component of the separated and purified solution. When introducing the solution from the device to the mass spectrometer via the splitter, a concentration detector for detecting the concentration of the separated and purified component was provided after the separation device, and the split ratio of the splitter was detected. A liquid chromatograph mass spectrometer, wherein the liquid chromatograph mass spectrometer is configured to vary according to the concentration and to vary the amount of liquid sent from the splitter to the mass spectrometer. 2. The method according to claim 1, wherein the liquid sending amount is 1/100 to 1 (ml / ml) depending on the concentration.
liquid chromatograph mass spectrometer that can be varied in the range of min). 3. The liquid chromatograph mass spectrometer according to claim 1, wherein the concentration detector is an ultraviolet (UV) detector. 4. The mass spectrometer according to claim 1, 2 or 3, further comprising a system for supplying a solvent amount between the splitter and the mass spectrometer, wherein the system is supplied to the mass spectrometer according to the concentration or the liquid sending amount. A liquid chromatograph mass spectrometer characterized by optimally controlling the total liquid volume.