JP2000131284A - Chromatograph mass spectrometer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To obtain an accurate chromatogram by removing the influence by a background noise. SOLUTION: Sample liquid comprising only a solvent not including a sample component is measured in the same measurement condition ahead of measurement of a target sample, and the data obtained by the measurement are stored in a storage part 24 corresponding to the retention time and the mass number. The data Sn includes the information on undesired peaks of impurities included in the solvent, components remaining in a column or the like. At the time of measurement of the target sample, the data of the same retention time and the same mass number are read out from the storage part 24 and subtracted by a subtraction processing part 22, relative to the data obtained by a detector. The data Su from which a background noise part is removed are accumulated in a storage part 25, and a data analysis part 23 forms an accurate mass spectrum or chromatogram based on the data Su.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a chromatograph mass spectrometer such as a gas chromatograph mass spectrometer (GC / MS) or a liquid chromatograph mass spectrometer (LC / MS).

[0002]

2. Description of the Related Art GC / MS has a structure in which a sample component is temporally separated by a chromatographic column, and each separated component is ionized and separated according to the mass number and detected. A mass spectrum is created by taking the mass number on the horizontal axis and the detected ion intensity on the vertical axis. Focusing on a certain mass number, the time (that is, the separation direction of the sample components) is taken on the horizontal axis, and the ion intensity is taken on the vertical axis. A mass chromatogram is created by taking the axis, and a total ion chromatogram (TIC) is created by taking time on the horizontal axis and ion intensity on the vertical axis regardless of the mass number. In the following description, a chromatogram indicates a total ion chromatogram unless otherwise specified.

[0003] In GC / MS, it is preferable to detect only ions generated from molecules of a sample component to be analyzed introduced into a column. However, in practice, an undesired peak is found in a mass spectrum due to various causes. appear. These are collectively referred to as background noise.If such noise is erroneously recognized as a peak due to the target sample component, it will interfere with qualitative analysis or quantitative analysis. Elimination has been done.

[0004]

The conventional technique for removing background noise is as follows. Usually, the solvent arrives at the column outlet earliest after the sample is injected at the column inlet, and the target component arrives later. Therefore, the mass spectrum data obtained before or after the target component elutes from the column (that is, when it is almost the baseline on the chromatogram) is stored in the memory, and this is regarded as background noise, It is uniformly subtracted from the mass spectrum data sequentially acquired during the period when the components elute.

However, according to such a method, for example, when a previously measured sample component remains in the column and elutes in the solvent during the next measurement and elutes near the peak of the target component, or When impurities are mixed in the solvent itself in the sample solution and the peak due to the impurities overlaps with the peak of the target component and elutes, such an undesired peak cannot be removed, and qualitative analysis or It may hinder quantitative analysis.

SUMMARY OF THE INVENTION The present invention has been made to solve the above-mentioned problems, and an object of the present invention is to provide a chromatographic mass spectrometer capable of obtaining an accurate chromatogram by more accurately eliminating background noise. It is to provide a device.

[0007]

Means for Solving the Problems A first chromatographic mass spectrometer according to the present invention, which has been made to solve the above problems, comprises the following steps: a) Prior to the measurement of a target sample, only a solvent containing no sample components A storage means for storing data obtained by performing chromatograph mass spectrometry under predetermined measurement conditions as noise data, and b) introducing the target sample under the predetermined measurement conditions. Calculating means for reading out noise data at the same retention time and the same mass number from the storage means and subtracting the same from the data obtained by performing the chromatograph mass spectrometry, and c) subtracting the data obtained by the calculating means. And a data processing means for creating a mass spectrum or a chromatogram based on the data.

[0008] Further, the second chromatogram mass spectrometer according to the present invention is the first chromatographic mass spectrometer, wherein the calculating means includes: b1) a certain chromatogram created based on noise data. Peak extraction means for finding one peak and using it as a reference peak; b2) peak detection for detecting a peak to be compared, which is a peak near the retention time of the reference peak, in a chromatogram created based on analysis data of a target sample And b3) correcting means for correcting the noise data in accordance with an intensity difference or an intensity ratio between a reference peak and a peak to be compared.

[0009]

BEST MODE FOR CARRYING OUT THE INVENTION In a first chromatographic mass spectrometer according to the present invention, prior to the measurement of a target sample, the same solvent and the same measurement conditions as when the target sample was introduced are used at least for the target sample. The analysis is performed over a period of time until the elution of the components is assumed to be complete. And
The data obtained as a result is stored in the storage means in association with the retention time and the mass number. Data obtained by such preliminary measurement is data on background noise including peaks due to residual components adhering to the inner wall of the column and impurities mixed into the solvent.

Subsequently, the target sample is introduced into the chromatograph unit, and the analysis is performed under the above-described measurement conditions. When data is obtained from the mass spectrometer during a certain retention time, the calculating means reads noise data having the same retention time and mass number as the data from the storage means, and subtracts the latter from the former. Thus, the data processing unit can create a mass spectrum or a mass chromatogram from which the influence of the background noise has been removed.

The arithmetic means may perform the subtraction processing (ie, perform real-time processing) each time new data is acquired during the analysis of the target sample, or may end the acquisition of all data once. After that, a subtraction process (that is, a batch process) may be performed.

When a target sample (the same sample or a different sample) is analyzed a plurality of times following the preliminary measurement, the residual components adhering to the inner wall of the column often decrease gradually as the analysis is repeated. In that case, the background noise should gradually decrease, and it is desirable to execute an operation taking such a fact into account in the above-described subtraction processing.

In the second chromatographic mass spectrometer according to the present invention, an impurity component corresponding to one peak appearing on a chromatogram obtained as a result of preliminary measurement is used as a reference for estimating the degree of influence of background noise. We are using. That is, the peak detecting means finds a peak (comparative peak) for the same component as the reference peak in the chromatogram to be analyzed, and the correcting means determines the degree of decrease in the intensity of the comparative peak with respect to the intensity of the reference peak by an intensity difference It is obtained as an intensity ratio, and the noise data is corrected accordingly. Then, the above-described subtraction processing is performed using the noise data thus corrected.
According to this configuration, when the impurity component is smaller than that at the time of the preliminary measurement when the target sample is analyzed, each noise data is reduced according to, for example, the intensity ratio, and the reduced noise data is used as the target. It is subtracted from the analytical data of the sample.
Therefore, more accurate denoising is achieved because the reduction of the residual components in the column is reflected in denoising.
Note that a peak having the maximum intensity in a chromatogram created based on the noise data may be used as the reference peak.

[0014] Further, when the reference peak and the peak of the target component overlap in the chromatogram to be analyzed, it is desirable not to judge erroneously that the influence of the background noise is large. Therefore, when the intensity of the peak to be compared exceeds the intensity of the reference peak, the correcting means may perform the process by regarding the intensity as the same as the intensity of the reference peak.

[0015]

According to the chromatographic mass spectrometer of the present invention, background noise is measured under exactly the same measurement conditions except that the sample component is not contained in the sample solution, and the retention time and mass of the background noise are measured. The background noise is subtracted for each data corresponding to the number, and a mass spectrum or a chromatogram is created based on the data. For this reason, a mass spectrum or a chromatogram excluding the effects of the residual components in the column and impurities contained in the solvent can be prepared, and the accuracy of the qualitative analysis and the quantitative analysis can be improved.

[0016]

DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS A GC / MS which is an embodiment of a chromatograph mass spectrometer according to the present invention will be described with reference to FIGS.

FIG. 1 is an overall configuration diagram of the GC / MS. In the GC section 1, a sample injection section centering on the sample vaporization chamber 2 is provided at the inlet end of the column 3 provided in the column oven 4, and the sample liquid injected into the sample vaporization chamber 2 is instantaneous. It is vaporized in between and is introduced into the column 3 on a carrier gas. While the vaporized sample passes through the column 3, various components contained in the sample are separated in a time direction and reach the outlet end of the column 3. The column oven 4 heats the column 3 according to a predetermined heating program in order to increase the speed of the component that passes slowly.

In the MS section 5, an ion source 7, an ion lens 8, a quadrupole filter 9, a detector 10 and the like are arranged inside an analysis chamber 6 to be evacuated. The outlet end of the column 3 is connected to an ion source 7, and the component molecules sequentially flowing out of the column 3 are ionized by the ion source 7 by collision with electrons or a chemical reaction. The generated ions fly out of the ion source 7, are converged by the ion lens 8 and accelerated moderately, and are introduced into the space in the longitudinal direction of the quadrupole filter 9.

A voltage obtained by superimposing a DC voltage and a high-frequency voltage is applied to the quadrupole filter 9. Only ions having a mass number (mass m / charge z) corresponding to the applied voltage selectively pass therethrough. Reach the detector 10. Since the mass number of ions passing through the quadrupole filter 9 depends on the applied voltage, the detector 10 can obtain an ion intensity signal in a predetermined mass range by scanning the applied voltage.

The output of the detector 10 is input to a data processing device 11 mainly composed of a personal computer. An external storage device 12, an operation unit 13, and a display unit 14 are connected to the data processing device 11. The data processing device 11 accumulates the signal obtained from the detector 10 in the external storage device 12, executes an arithmetic process based on the signal, and outputs the result to the display unit 14. For example, a mass spectrum is created by taking the ion intensity and the mass number on the vertical axis when the mass scanning is performed at a certain time as described above. When mass scanning is repeatedly performed at predetermined time intervals,
Many mass spectra corresponding to various components sequentially flowing out of the column 3 can be obtained.

After obtaining such a mass spectrum,
A mass chromatogram can be obtained by developing and drawing the ion intensity in the time axis direction by focusing on a certain mass number. Further, a total ion chromatogram can be obtained by calculating the total of the ion intensities each time a mass spectrum is obtained and developing and drawing out in the time axis direction. Further, the data processing device 11 finds a target component from such a chromatogram and performs a quantitative calculation of the component.

As described above, the signal obtained by the detector 10 includes various background noises. Therefore,
The data processing device 11 performs the above-described various graph creation processing after performing the background noise removal processing on the detection signal.

FIG. 2 is a configuration diagram of a main part relating to background noise removal processing. The data processing device 11 includes an A / D converter 20 that converts an analog detection signal Sd input from the detector 10 into digital data, and an input / output controller that controls input and output of data to and from the external storage device 12. 21, a subtraction processing unit 22 for executing a subtraction process, a data analysis unit 23 for creating a mass spectrum, a mass chromatogram, a total ion chromatogram, etc. and executing various analysis processes. External storage device 12
Includes a noise data storage unit 24 for storing noise data representing background noise, and a spectrum data storage unit 25 for storing data after the background noise removal processing is performed. .

Hereinafter, the operation of the GC / MS of this embodiment will be described with reference to FIGS.
This will be described with reference to FIG.

First, prior to the measurement of the target sample,
Background noise data is stored in the noise data storage unit 2
4 For this purpose, the same solvent as used when introducing the target sample is analyzed under the same measurement conditions. That is, the carrier gas at a constant flow rate is supplied to the sample vaporization chamber 2.
Through the column 3, and a sample solution containing only a solvent is injected into the sample vaporization chamber 2 at a predetermined timing. Generally, the vaporized solvent passes through the column 3 quickly and
When reaching the outlet end, if impurities are mixed in the solvent,
The impurities cause adsorption and desorption on the inner wall of the column 3 when passing through the column 3. Further, when the impurities include a plurality of components, they are separated temporally, and the column 3 is delayed behind the solvent.
Reach the exit end. If the sample component analyzed before remains on the inner wall of the column 3, the sample component volatilizes and is carried toward the outlet of the column 3 when the solvent passes.

The gas flowing out of the column 3 is introduced into the MS section 5, and mass scanning over a predetermined mass range is repeatedly performed at predetermined time intervals. These parameters can be set in advance by the user, for example, 0.5
Mass scanning may be performed at intervals of seconds for a scanning time of 0.1 second. During one mass scan, the detector 10
The detection signal Sd obtained in step (1) is sampled at predetermined time intervals by the A / D converter 20 and converted into digital data.
4 are sequentially stored. At this time, the noise data Sn is associated with the retention time during mass scanning (elapsed time from the sample injection time) and the mass number, that is, the noise data storage unit 2 so that it can be accessed with these parameters.
4 is stored. At the same time as writing the noise data to the noise data storage unit 24, the data is sent to the data analysis unit 23, and a mass spectrum and a chromatogram of the background noise are created and displayed on the screen of the display unit 14. Is also good.

For example, when a chromatogram of the background noise is created and drawn, as shown in FIG. 3A, peaks due to undesired various components appear in addition to the peak due to the solvent which appears first. FIG. 3B shows a mass spectrum generated at the retention time at which the peak occurs. Since all such noise data is stored in the noise data storage unit 24, even after the measurement is completed, the noise data can be read out as needed to render a mass spectrum or a chromatogram.

When the preliminary measurement as described above is completed, the measurement of the target sample is performed under the same measurement conditions as the preliminary measurement. At this time, while the target sample component is separated in the time direction while passing through the column 3, undesired components mixed in the solvent are also separated in the same manner as in the above measurement. In addition, since the residual components on the inner wall of the column 3 usually do not completely flow out in the above-mentioned single measurement, the residual components are similarly volatilized in the solvent and carried to the outlet of the column 3 during this measurement. Therefore, the gas flowing out of the column 3 contains both sample components and undesired components.

When such a gas is introduced into the MS section 5 and the above-described mass scanning is performed, the detection signal Sd obtained by the detector 10 is converted into digital data by the A / D conversion section 20. And is sequentially input to the subtraction processing unit 22. Further, noise data Sn corresponding to the same holding time as the data acquired at this time is read from the noise data storage unit 24 and input to the subtraction processing unit 22. Subtraction processing unit 2
2 subtracts the noise data Sn for the same mass number from the acquired data, and stores the subtraction result in the spectrum data storage unit 25 as the spectrum data Su. If the subtraction result is negative, the spectrum data Su at that time is set to 0.

For example, when a chromatogram is prepared based on the data obtained in the analysis of the target sample, the result is as shown in FIG. 3C, and the mass spectrum having the same retention time as that of FIG. Is as shown in FIG. 3 (d). It is not necessary to actually render such a chromatogram or mass spectrum on the screen of the display unit 14.

According to the background noise removal processing as described above, the spectrum data is obtained by subtracting the background noise data for each retention time and for each mass number, and thus is created based on the spectrum data Su. The mass spectrum shown in FIG.
The shape is obtained by subtracting the mass spectrum of FIG. 3B from the mass spectrum of FIG. A chromatogram created based on such spectral data is shown in FIG.
As shown in (b), the chromatogram of FIG. 3 (c) is subtracted from the chromatogram of FIG. 3 (c), and undesired peaks due to the above-described factors are eliminated.

In the above embodiment, the data obtained by the detector 10 is stored as it is as noise data. However, the data may be stored after performing a predetermined process. For example, in a case where mass scanning is performed a plurality of times in a short time, and data for each mass number obtained thereby are averaged (or a process corresponding thereto) to obtain spectral data, such averaging process is performed. Later data may be accumulated as noise data. In this way, the amount of data to be stored can be reduced, and the effect of sudden noise can be reduced.

Next, GC / M according to another embodiment of the present invention
S will be described. FIG. 5 is a configuration diagram of a main part relating to background noise removal processing according to this embodiment. In the GC / MS according to this embodiment, the background noise removal processing cannot be performed in real time as in the above embodiment, and therefore, the spectrum data (noise removal) acquired by measuring one or more target samples to be analyzed is not possible. The external storage device 12 includes a spectrum data storage unit 25 for storing unprocessed data) and a corrected spectrum data storage unit 26 for storing spectrum data subjected to noise removal processing.

FIG. 6 is a flowchart of the background noise removal processing in this embodiment, and FIG. 7 is an explanatory diagram of the operation of the background noise removal processing. Hereinafter, the operation of the background noise removal processing of this embodiment will be described focusing on the differences from the processing in the above embodiment.

As in the above example, prior to the measurement of the target sample, the same solvent as that used when introducing the target sample is analyzed under the same measurement conditions, and the resulting background noise data is obtained. The noise data is stored in the noise data storage unit 24. Thereafter, the measurement of one or more target samples is performed under the same measurement conditions as the preliminary measurement, and is temporarily stored in the spectrum data storage unit 25.

When the background noise removal processing is started, the data analysis unit 23
, The noise data Sn is sequentially read out to create a chromatogram as shown in FIG. Then, a peak is detected in this chromatogram, a peak having the maximum intensity is found, excluding the peak of the solvent, and the retention time ta and the intensity Ia of the peak are obtained and stored (step S1).

Next, the data analysis unit 23 sequentially reads out the spectrum data Su to be analyzed from the spectrum data storage unit 25 and creates a chromatogram as shown in FIG. And in this chromatogram,
A unique peak existing in a time range set with a predetermined time width ± Δt with respect to the holding time ta is found, and the intensity Ib of the peak is obtained (step S2). This peak is not considered to be a target component contained in the target sample, but to be an undesired peak due to a residual component.

Next, the data analyzer 23 calculates an intensity ratio R between the peak intensity Ib and the previous peak intensity Ia (step S3). When such a peak is due to a residual component, as the analysis proceeds, the residual component gradually dissolves in the solvent and its concentration decreases, so that the intensity of the peak often decreases. Therefore, usually, the intensity ratio R should be close to 1 in the measurement performed immediately after the preliminary measurement, and should be close to 0 as the measurement is performed later in time.
However, if the peak selected here overlaps with the peak of the target component, the intensity Ib becomes the intensity Ia.
May be larger than Therefore, if the intensity ratio R is 1
It is determined whether or not this is the case (step S4). If R is 1 or more, R is set to 1 (step S5).
That is, the intensity ratio R is always set to a value of 1 or less.

When the intensity ratio R is determined in this way, the subtraction processing unit 22 calculates the noise data Sn corresponding to the same mass number and the same holding time from the spectrum data Su.
Is subtracted by the intensity ratio R, and the result is stored in the corrected spectrum data storage unit 26 as corrected spectrum data Su '(step S6). If the subtraction result is negative, the corrected spectrum data Su 'at that time may be set to 0. The data analysis unit 23 creates a mass spectrum or a chromatogram using the corrected spectrum data Su ′ and renders it on the display unit 14 (step S7).

According to such a background noise removal process, the influence of the residual component in the column, which is the main cause of the noise, is reduced although it is eluted and reduced in the course of a plurality of measurements. Excessive subtraction is not performed due to the assumption that the value is large. Therefore, only the background noise is more accurately removed.

In the above description, the peak having the maximum intensity on the chromatogram obtained by the preliminary measurement is used. This is because the detection is easy even when the intensity is reduced. Need not be. For example, if the intensity ratio R is 1 or more in step S4 in the flowchart shown in FIG. 6, it is highly possible that the peaks due to the components contained in the target sample overlap as described above. If the processing after step S4 is performed using this, accuracy may be lacking. Therefore, in such a case, the process returns to step S1 again, extracts the next peak having the second largest intensity on the chromatogram obtained by the preliminary measurement, and executes the processing from step S2 onward using the peak. You may.

The above embodiment is merely an example, and it is apparent that changes and modifications can be made within the scope of the present invention.

[Brief description of the drawings]

FIG. 1 is an overall configuration diagram of a GC / MS according to an embodiment of the present invention.

FIG. 2 is a configuration diagram of a main part relating to background noise removal processing in the present embodiment.

FIG. 3 is an explanatory diagram of an operation of background noise removal processing in the present embodiment.

FIG. 4 is an explanatory diagram of an operation of background noise removal processing in the present embodiment.

FIG. 5 is a configuration diagram of a main part relating to background noise removal processing in a GC / MS according to another embodiment of the present invention.

FIG. 6 is a flowchart of background noise removal processing in another embodiment.

FIG. 7 is an explanatory diagram of an operation of background noise removal processing in another embodiment.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 ... Gas chromatograph (GC) part 2 ... Sample vaporization chamber 3 ... Column 6 ... Mass spectrometry (MS) part 10 ... Detector 11 ... Data processing device 12 ... External storage device 20 ... A / D conversion part 21 ... Input / output control Unit 22: Subtraction processing unit 23: Data analysis unit 24: Noise data storage unit 25: Spectrum data storage unit 26: Modified spectrum data storage unit

──────────────────────────────────────────────────続 き Continued on the front page (51) Int.Cl. ⁷ Identification symbol FI Theme coat ゛ (Reference) G01N 30/86 G01N 30/86 H

Claims (2)

[Claims] 1. a) Prior to measurement of a target sample, data obtained by introducing only a solvent containing no sample component and performing chromatographic mass spectrometry under predetermined measurement conditions is stored as noise data. Storage means for storing the noise data at the same retention time and the same mass number with respect to the data obtained by introducing the target sample and performing chromatographic mass spectrometry under the predetermined measurement conditions. A chromatographic mass spectrometer comprising: a calculating means for reading out and subtracting from the means; and c) a data processing means for creating a mass spectrum or a chromatogram based on the data subjected to the subtraction processing by the calculating means. 2. The calculating means comprises: b1) a peak extracting means for finding a certain peak in a chromatogram created based on the noise data and setting it as a reference peak; and b2) analyzing a target sample based on analysis data. Peak detection means for detecting a peak to be compared which is a peak near the retention time of the reference peak in the created chromatogram; b3) the noise data according to an intensity difference or an intensity ratio between the reference peak and the peak to be compared. The chromatograph mass spectrometer according to claim 1, further comprising: correction means for correcting.