JP3867426B2 - Chromatograph mass spectrometer - Google Patents

Description

[0001]
BACKGROUND OF THE INVENTION
The present invention relates to a chromatograph mass spectrometer, and more particularly to a liquid chromatograph mass spectrometer.
[0002]
[Prior art]
In general, a liquid chromatograph mass spectrometer is a liquid chromatograph unit (LC unit) that separates a sample into components by flowing a liquid (mobile phase) into which a sample has been injected through a column, and each sample separated by the LC unit. The components are ionized in the ionization chamber, the generated ions are separated by mass number (m / z) and detected by the ion detector, and the output signal of the ion detector is processed Data processing unit that processes the data obtained and outputs the results to an output device (image display device, printing device, etc.) in the form of a mass spectrum, mass chromatogram (MC), total ion chromatogram (TIC), etc. Is provided.
[0003]
[Problems to be solved by the invention]
In the ionization chamber of the MS unit, each sample component separated in the LC unit is ionized by a predetermined method, and various ions are generated (these ions are hereinafter referred to as an analysis target ion group). However, ions generated in the ionization chamber are not only ion ions to be analyzed, but also, for example, substances used as mobile phases in the LC section are partially ionized. In addition, the molecules of the substance may aggregate by using the generated ions as nuclei to form cluster ions. Various ions other than the analysis target ion group (hereinafter referred to as non-analysis target ion group) are detected by the ion detector of the MS unit together with the analysis target ion group. Therefore, the chromatogram obtained by processing the output signal of the ion detector appears in a form in which the peak of the analysis target ion is superimposed on the background noise caused by the non-analysis target ion group. In such a chromatogram, if the total amount of target ions detected by the ion detector at a certain point in time is very small, the peak height corresponding to the ions in the chromatogram will be low, and background noise will be reduced. There is a possibility that it cannot be distinguished from the peak of minute fluctuations.
[0004]
The above-described problems can occur not only in a liquid chromatograph mass spectrometer but also in a gas chromatograph mass spectrometer, for example. However, in liquid chromatographs, the type of substance used as a mobile phase is much more than that in gas chromatographs, and the background noise generation method varies depending on the difference in the substance, so the problem is particularly problematic. Serious.
[0005]
The present invention has been made in order to solve such problems, and the object of the present invention is to avoid the influence of a group of non-analyzed ions caused by a substance used as a mobile phase, in a sample. It is an object of the present invention to provide a chromatographic mass spectrometer that can detect even a trace amount component.
[0006]
[Means for Solving the Problems]
The chromatograph mass spectrometer according to the present invention made to solve the above problems is used as a mobile phase in a chromatograph section from an original mass spectrum obtained by processing an output signal of an ion detector of a mass spectrometer section. And a chromatogram creating means for creating a chromatogram using a difference mass spectrum obtained by subtracting a mass spectrum of ions caused by a substance to be obtained.
[0007]
DETAILED DESCRIPTION OF THE INVENTION
The chromatogram creation means of the chromatograph mass spectrometer according to the present invention uses a mass spectrum (original mass spectrum) obtained by processing the output signal of the ion detector of the mass analyzer as a mobile phase in the chromatograph. A difference mass spectrum is derived by subtracting the mass spectrum of ions (non-analysis target ion group) caused by the substance to be generated, and a chromatogram (TIC or MC) is created using the difference mass spectrum. The data processing means for performing such processing can be configured using a commonly used computer.
[0008]
As one form of this invention,
Storage means for storing mass spectrum data of various substances used as a mobile phase in the chromatograph section;
A mobile phase specifying means for specifying a substance selected as a mobile phase in actual measurement,
The data processing means reads out the mass spectrum data of the substance specified by the mobile phase specifying means from the storage means, and derives the difference mass spectrum by subtracting the mass spectrum obtained from the data from the original mass spectrum. And a chromatograph mass spectrometer having a configuration of
[0009]
In the chromatograph mass spectrometer of the above-mentioned form, the mobile phase specifying means displays the substance names stored in the storage means (hard disk or the like) on the image display means (CRT or the like) in a list format, for example. When a substance that is actually used (or used) is selected from a list by operating an input means (keyboard, mouse, etc.), a process for sending data specifying the substance to the data processing means is performed by a computer. Can be configured as a program to be executed. Further, in the case of an apparatus having a mechanism that automatically selects a desired substance from a plurality of substances prepared in advance and supplies the selected substance to the chromatograph unit, the mobile phase specifying means takes in an operation signal of the mechanism, and the operation signal Based on the above, it may be configured to identify the substance selected as the mobile phase.
[0010]
In the chromatograph mass spectrometer of the above-described form, the mass spectrum data of the non-analysis target ion group necessary for derivation of the differential mass spectrum is stored in advance in the storage means as follows. That is, for example, at the time of sample preparation, a signal output from the ion detector of the mass analysis unit is collected while flowing a substance used as a mobile phase to the column of the chromatograph unit without putting the sample therein. By processing this output signal, the mass spectrum of the mobile phase substance is obtained, and the data is stored in a storage means such as a hard disk. In this way, mass spectrum data is obtained for every substance used as a mobile phase in the chromatograph section and stored in the storage means. In actual sample analysis, the substance selected as the mobile phase is specified by the mobile phase specifying means, and the mass spectrum data of the substance is read from the storage means and processed to obtain a mass spectrum. A difference mass spectrum is obtained by subtracting this mass spectrum from the original mass spectrum.
[0011]
By the way, in measurement using a liquid chromatograph mass spectrometer, gradient measurement using a mobile phase formed by mixing a plurality of different solvents may be performed. In view of this, in the chromatograph mass spectrometer of the above aspect, when the chromatograph part is a liquid chromatograph, the data processing means performs a gradient measurement using a mobile phase formed by mixing a plurality of solvents. In addition, mass spectrum data of each solvent substance included in the mobile phase at each measurement time point is read from the storage means, and a weighted average of the mass spectra is calculated from the composition of each solvent substance in the mobile phase at the measurement time point. Preferably, the ratio is obtained as a weighting factor, and the mass spectrum is subtracted from the original mass spectrum at the time of measurement.
[0012]
As another form of the present invention,
The data processing means is a mass spectrum data obtained by processing a signal output from the ion detector in a time zone in which a component separated from a sample is not included in a mobile phase flowing into an ionization chamber during actual measurement. Is stored as background noise data in the storage means or in a second storage means provided separately from the storage means, and when the differential mass spectrum is derived, the mass spectrum obtained from the background noise data is subtracted from the original mass spectrum. And a chromatograph mass spectrometer configured as described above.
[0013]
【The invention's effect】
As described above, in the chromatograph mass spectrometer according to the present invention, the back-up by the non-analyzed ion group caused by the substance used as the mobile phase is obtained from the original mass spectrum obtained by processing the output signal of the ion detector. Create a chromatogram after removing ground noise. Since only the peak corresponding to the analysis target ion group appears in the chromatogram created in this way, even a trace amount component contained in the sample can be reliably detected.
[0014]
【Example】
The data processing procedure in the chromatograph mass spectrometer according to the present invention will be described in more detail with reference to the drawings.
[0015]
First, it is assumed that when a sample is analyzed by a conventional method, a total ion chromatogram as shown in FIG. 1 (however, when the sample is introduced into the mobile phase is t = 0) is obtained. In this chromatogram, two distinct peaks P1 and P2 appear at retention times t1 and t2, respectively, while no other distinct peaks appear in the rest of the chromatogram.
[0016]
Next, it is assumed that the mass spectrum at the retention time t0 included in the time zone from the sample input to the mobile phase until the detection of the first peak P1 is as shown in FIG. At this point, the mobile phase flowing into the ionization chamber does not yet contain the sample separation component. Therefore, the mass spectrum S0 in FIG. 2 is a mass spectrum of the non-analyzing target ion group caused by the mobile phase. On the other hand, it is assumed that the mass spectrum at the holding time t1 when the peak P1 appears is as shown in FIG. At this time, in addition to the mass spectrum S0 of the non-analysis target ion group already described in FIG. 2A, the mass spectrum S1 of the analysis target ion group constituting the peak P1 also appears.
[0017]
FIG. 3 is a mass spectrum obtained by subtracting the mass spectrum of FIG. 2A from the mass spectrum of FIG. 2B, which is the difference mass spectrum at the retention time t1. In this differential mass spectrum, only the mass spectrum S1 corresponding to the peak P1 appears. In this way, a differential mass spectrum is obtained for each holding time.
[0018]
The total ion chromatogram created using the differential mass spectrum is, for example, as shown in FIG. Since the chromatogram of FIG. 4 does not include a background noise fluctuation component due to the non-analyzed ion group, (1) not only the shapes of the two peaks P1 and P2 appear more correctly. (2) In the chromatograph of FIG. 1, a minute third peak P3 that is buried in the fluctuation component of the baseline and difficult to identify appears at the retention time t3. Thus, if a total ion chromatogram is created using a difference mass spectrum, a better-quality chromatogram can be obtained than by the conventional method. In addition, it cannot be overemphasized that such an effect is acquired similarly also in preparation of a mass chromatogram.
[0019]
In the above description, the differential mass spectrum is created using the mass spectrum obtained by processing the signal output from the ion detector before the first peak P1 is detected. You may use the mass spectrum obtained by processing the signal which an ion detector outputs in another time slot | zone which does not appear.
[0020]
Next, consider the case where gradient measurement is performed using a liquid chromatograph mass spectrometer. In the measurement, a mobile phase formed by mixing two solvents A and B is used, and the composition ratio is changed as shown in FIG. 5 according to time. That is, at the start of the measurement, the composition ratio of the mobile phase is solvent A: solvent B = 100: 0 (%), but the proportion of solvent B increases in proportion to the elapsed time thereafter, and solvent A: Solvent B = 0: 100 (%). Note that the composition ratio of the mobile phase at time t6 in FIG. 5 is solvent A: solvent B = 50: 50 (%).
[0021]
First, the signal output from the ion detector of the mass analysis unit is collected while flowing the solvent A through the column of the chromatograph unit without putting the sample therein. By processing this output signal, the mass spectrum of the solvent A is obtained, and the data is stored in a storage device such as a hard disk. Similarly, the mass spectrum data of the solvent B is also stored in the storage device. Using the data thus stored, for example, the mass spectrum of the non-analyzed target ion group at time t6 in FIG. 5 is obtained as follows. That is, the weighted average of the mass spectrum of the solvent A (FIG. 6 (a)) and the mass spectrum of the solvent B (FIG. 6 (b)) obtained by processing the data stored in the storage device is calculated at each time t6. The solvent composition ratio (both 0.5) is calculated as a weighting factor. The mass spectrum thus obtained is shown in FIG.
[Brief description of the drawings]
FIG. 1 is a total ion chromatogram obtained by analyzing a sample by a conventional method.
2A is a mass spectrum at a retention time t0 in FIG. 1, and FIG. 2B is a mass spectrum at a retention time t1 at which a peak P1 appears.
3 is a differential mass spectrum obtained by subtracting the mass spectrum of FIG. 2A from the mass spectrum of FIG.
FIG. 4 is a total ion chromatogram of the sample prepared using a differential mass spectrum.
FIG. 5 is a graph showing changes in the composition ratio of the mobile phase in gradient measurement using two solvents A and B.
6A is a mass spectrum of solvent A, FIG. 6B is a mass spectrum of solvent B, and FIG. 6C is a mass spectrum of a mobile phase at time t6 in FIG.

Claims (2)

Using the differential mass spectrum obtained by subtracting the mass spectrum of ions caused by the substance used as the mobile phase in the chromatograph from the original mass spectrum obtained by processing the output signal of the ion detector of the mass analyzer A chromatograph mass spectrometer equipped with a chromatogram creation means for creating a chromatogram,
a) storage means for storing mass spectrum data of various substances used as a mobile phase in the chromatograph section;
b) a mobile phase identification means for identifying the substance selected as the mobile phase in the actual measurement;
The chromatogram creating means reads out the mass spectrum data of the substance specified by the mobile phase specifying means from the storage means, and subtracts the mass spectrum obtained from the data from the original mass spectrum to obtain the difference mass spectrum. A chromatographic mass spectrometer characterized by being derived.   When the chromatogram creation means performs a gradient measurement using a mobile phase formed by mixing a plurality of solvents, the mass spectral data of each solvent substance contained in the mobile phase at each measurement time point is read from the storage means, The weighted average of those mass spectra is obtained by obtaining the composition ratio of each solvent substance in the mobile phase at the time of measurement as a weighting factor and subtracting the mass spectrum from the original mass spectrum at the time of measurement. The chromatograph mass spectrometer according to claim 1, wherein a chromatogram is created using a difference mass spectrum.

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