JP2017161442A - Chromatograph mass analysis data processing device - Google Patents

Abstract

PROBLEM TO BE SOLVED: To accurately determine the quality of a compound to be quantified on the basis of data obtained by SIM measurement and MRM measurement even when there are many impurities included in a sample.SOLUTION: SIM measurement by a GC-MS measurement system 1 is executed on a sample and scan measurement by a GCxGC-MS measurement system 2 is performed on the same sample. A mass chromatogram creation unit 35 creates a mass chromatogram in an m/z that corresponds to a target compound on the basis of data obtained by the SIM measurement, and a two-dimensional chromatogram creation unit 37 creates a two-dimensional chromatogram by TIC on the basis of the data obtained by the scan measurement. A chromatogram time axis adjustment unit 40 adjusts the time axis of the mass chromatogram and the holding time axis (horizontal axis) of the primary column of the two-dimensional chromatogram using the retention index of an n-alkane, and a chromatogram display processing unit 41 displays the two chromatograms lengthwise one below another along the same time axis. In this way, it is possible to confirm whether peaks on the mass chromatogram used for quantification derive from a single compound or not.SELECTED DRAWING: Figure 1

Description

  The present invention relates to a chromatograph mass spectrometry data processing apparatus for processing data collected by a chromatograph mass spectrometer such as a gas chromatograph mass spectrometer (GC-MS) or a liquid chromatograph mass spectrometer (LC-MS), More particularly, the present invention relates to a chromatographic mass spectrometry data processing apparatus suitable for quantitative analysis in which a compound in a sample is quantified using a chromatographic mass spectrometer. In the present specification, the “mass spectrometer” includes a mass spectrometer capable of performing MS / MS analysis such as a triple quadrupole mass spectrometer.

  In recent years, selected ion monitoring (SIM) measurement in a gas chromatograph mass spectrometer (GC-MS) combining a gas chromatograph (GC) and a quadrupole mass spectrometer in order to quantify a specific compound contained in a sample. Or multiple reaction monitoring (MRM) measurement in a gas chromatograph mass spectrometer (GC-MS / MS) combining a gas chromatograph (GC) and a triple quadrupole mass spectrometer or a Q-TOF mass spectrometer. It is frequently used. In particular, MRM measurement has high ion selectivity and high detection sensitivity (on the order of fg), so it can be used for quantification of target compounds in samples with many contaminants and multi-component simultaneous analysis in samples containing many compounds. Widely used.

  When performing SIM measurement or MRM measurement in a gas chromatograph mass spectrometer, the analyst usually provides a measurement time range based on the retention time of the compound and the mass charge of ions derived from the compound for each compound to be measured. The ratio or MRM transition (combination of precursor ion and product ion mass-to-charge ratio) is set in the apparatus as measurement parameters in advance. Then, measurement targeting the mass-to-charge ratio or MRM transition set corresponding to the measurement time range is performed in the measurement time range set as the measurement parameter, and the ion intensity of the corresponding ion is detected. .

  That is, at the time of SIM measurement or MRM measurement, the target compound that is the measurement target is basically known. However, in some cases, impurities unexpected by the analyst may be detected in the same measurement time range and the same mass-to-charge ratio as the target compound. Therefore, it is necessary to confirm whether the compound detected in the mass to charge ratio targeted by SIM measurement or MRM measurement is truly the target compound. For this purpose, in the apparatus described in Patent Document 1, SIM / MRM measurement and scan / SIM simultaneous measurement in which scan measurement over a predetermined mass-to-charge ratio range is alternately performed in a short time. Can be done.

  In the simultaneous scan / SIM measurement or the simultaneous scan / MRM measurement, a mass spectrum over a predetermined mass-to-charge ratio range can be obtained by the scan measurement substantially simultaneously with the SIM measurement or the MRM measurement. Therefore, by performing a library search based on the peak pattern on the mass spectrum, a compound that appears in the vicinity of the retention time can be identified. Thereby, it is possible to confirm whether or not the mass-to-charge ratio targeted by SIM measurement or MRM measurement is truly derived only from the target compound, that is, qualitative confirmation of the target compound can be performed.

  However, since the time for detecting one kind of ions is short in the scan measurement, the detection sensitivity is not so high. In particular, the detection sensitivity of scan measurement is considerably inferior to that of MRM measurement. Therefore, when the concentration of the target compound in the sample is low or there are many impurities, the influence of the peaks derived from the impurities and other noise peaks in the mass spectrum becomes relatively large, and even if a library search is performed, the compound Is difficult to identify with high accuracy. As described above, since MRM measurement is often used when there are many contaminants, the qualitative performance deteriorates due to the presence of contaminants. In the scan measurement in the simultaneous scan / MRM measurement, the target compound to be measured is measured. It is not enough to ensure qualitative confirmation.

JP 2013-205323 A JP 2013-68444 A

As described above, although SIM measurement and MRM measurement in GC-MS are excellent in quantification, qualitative information such as overlapping of peaks derived from other compounds cannot be obtained. It is necessary to confirm whether or not is truly derived only from the target compound. Although qualitative information can be obtained by scanning measurement in simultaneous scanning / SIM or simultaneous scanning / MRM measurement, the qualitative performance is insufficient in situations where there are many impurities.
The GC / MS analysis has been described so far, but the situation is the same not only in the GC / MS analysis but also in the LC / MS analysis.

  The present invention has been made to solve these problems, and its main purpose is to perform quantitative analysis using SIM measurement and MRM measurement in chromatograph mass spectrometers such as GC-MS and LC-MS. A chromatographic mass that enables accurate qualitative confirmation of a target compound even when there are many impurities in the sample, when the number of compounds to be measured is large, or when the concentration of the target compound is low. An analysis data processing apparatus is provided.

  Comprehensive two-dimensional GC (also called “GC × GC”) is known as a method for separating compounds with high resolution when there are many compounds in the sample or when there are multiple compounds with similar retention times. (See Patent Document 2).

  Comprehensive two-dimensional GC first separates a plurality of compounds in a sample with a first-dimensional column (hereinafter referred to as “primary column”), and introduces the eluted components into a modulator. The modulator collects the introduced components at regular time intervals (usually several seconds to several tens of seconds; this time is usually referred to as “modulation time”), and then removes it with a very narrow time bandwidth. The operation of “introducing into the“ secondary column ”” is repeated. In general, in the primary column, the component separation is performed under separation conditions that allow the elution to be performed at the same level or slightly slower than normal GC. On the other hand, as the secondary column, a column having a polarity different from that of the primary column and having a short inner diameter is used, and the component separation is performed under such a condition that the elution is completed within the modulation time. As a result, in the comprehensive two-dimensional GC, a plurality of compounds in which peaks are overlapped without being separated in the primary column can be separated in the secondary column, and the separation performance is greatly improved as compared with the normal GC.

  For this reason, even in the case of a complex sample in which peaks are overlapped with normal GC or a sample with many impurities, according to comprehensive two-dimensional GC, reliable qualification can be achieved by separating the target compound from other compounds. . Therefore, the present inventor has come up with the idea of using a comprehensive two-dimensional GC for qualitative confirmation of a target compound in quantitative analysis using SIM measurement or MRM measurement in GC-MS. However, in that case, there are the following problems.

  In quantitative analysis by SIM measurement or MRM measurement in GC-MS, a mass chromatogram of the target compound-derived mass-to-charge ratio or MRM transition is created, and a quantitative value is calculated based on the peak area on the mass chromatogram. On the other hand, in the comprehensive two-dimensional GC and the comprehensive two-dimensional LC, usually, the horizontal axis represents the retention time of the primary column and the vertical axis represents the retention time of the secondary column, and the signal intensity is indicated by a contour line or a color scale. A dimensional chromatogram is created. Since a plurality of compounds that are not sufficiently separated in the primary column appear at different positions on the holding axis of the secondary column, that is, on the vertical axis, a plurality of blobs (on the vertical axis at a certain holding time) By checking whether or not a two-dimensional peak) exists, it is possible to determine whether a compound that is not separated in the primary column is actually one compound or a plurality of compounds. Therefore, if the time axis of the mass chromatogram matches the time axis (horizontal axis) of the primary column of the two-dimensional chromatogram, is the peak observed on the mass chromatogram derived from one compound? It can be determined from the two-dimensional chromatogram whether or not a plurality of compounds are overlapped.

  However, in many cases, the column used in the GC-MS and the primary column of the comprehensive two-dimensional GC are the same or similar, but usually the same in the GC-MS and the comprehensive two-dimensional GC. The retention times of the compounds are not the same. This is because it is difficult to match the separation conditions such as the heating time. Specifically, in the comprehensive two-dimensional GC analysis, the temperature increase in the normal GC / MS (or GC / MS / MS) analysis is performed in order to widen the peak width in the primary column and secure a sufficient number of data sampling points. In general, the rate of temperature rise is relatively slow (eg 3 ° C./min) compared to the rate (eg 10 ° C./min). Therefore, the retention time in comprehensive two-dimensional GC analysis is considerably slower than the retention time in GC / MS (or GC / MS / MS) analysis. As a result, the time axis of the mass chromatogram by GC-MS does not coincide with the time axis of the primary column of the two-dimensional chromatogram by comprehensive two-dimensional GC.

In order to solve such a problem, the chromatograph mass spectrometry data processing apparatus according to the present invention,
a) Mass-to-charge ratio or MRM corresponding to a specific compound based on data obtained by performing selective ion monitoring (SIM) measurement or multiple reaction monitoring (MRM) measurement on a target sample with a chromatographic mass spectrometer. A mass chromatogram creation unit for creating a mass chromatogram in a transition;
b) Based on the data obtained by scanning the target sample with a comprehensive two-dimensional chromatograph mass spectrometer, the retention time in the first dimension column is orthogonal to the retention time in the second dimension column. A two-dimensional chromatogram creating unit for creating a two-dimensional chromatogram having two axes,
c) Adjust one or both of the time axes so that the appearance time of the same compound matches on the time axis of the mass chromatogram and the retention time axis of the first dimension column of the two-dimensional chromatogram. A time axis adjustment unit;
d) a chromatogram display processing unit that displays the mass chromatogram and the two-dimensional chromatogram, the time axis of which has been adjusted by the time axis adjustment unit, aligned on the screen of the display unit and displayed.
It is characterized by having.

  Here, the chromatograph mass spectrometer is a gas chromatograph mass spectrometer or a liquid chromatograph mass spectrometer, and the mass spectrometer includes a mass spectrometer capable of MS / MS analysis. The comprehensive two-dimensional chromatograph mass spectrometer is a comprehensive two-dimensional gas chromatograph mass spectrometer or a comprehensive two-dimensional liquid chromatograph mass spectrometer.

In the chromatograph mass spectrometry data processing apparatus according to the present invention, the time axis adjustment unit uses the results obtained by measuring the reference compound with the chromatograph mass spectrometer and the comprehensive two-dimensional chromatograph mass spectrometer, The time axis of one or both of the mass chromatogram and the two-dimensional chromatogram can be adjusted.
When the chromatograph mass spectrometer is a gas chromatograph mass spectrometer and the comprehensive two-dimensional chromatograph mass spectrometer is a comprehensive two-dimensional gas chromatograph mass spectrometer, a retention index is known as a reference compound. N-alkanes may be used.

  The chromatogram display processing unit renders the mass chromatogram and the two-dimensional chromatogram, the time axis of which has been adjusted by the time axis adjustment unit, displayed on the screen of the display unit along the horizontal axis, that is, the vertical direction along the time axis. . In such a display, a peak in the mass chromatogram and a blob in the two-dimensional chromatogram can be associated on the same horizontal axis. Therefore, the analyst should look at this display screen to confirm how many blobs are present on the two-dimensional chromatogram at the same position on the horizontal axis as the peak derived from the target compound observed on the mass chromatogram. Thus, it can be easily and visually determined whether or not the peak derived from the target compound is truly derived from only the target compound (whether other impurities overlap).

The first aspect of the chromatograph mass spectrometry data processing apparatus according to the present invention is as follows.
e) a spectrum library in which mass spectrum information is stored in association with compound information;
f) a selection instruction unit for the analyzer to select and instruct an arbitrary blob on the two-dimensional chromatogram displayed on the screen of the display unit;
g) Acquire spectrum data obtained at the time position where the blob instructed by the selection instruction unit exists, and collate the mass spectrum created based on the data with the mass spectrum stored in the spectrum library A library search unit for obtaining compound information corresponding to the blob;
It is good to set it as the structure further provided.

  For example, if only one blob is observed on the two-dimensional chromatogram at the same position on the horizontal axis as the peak derived from the target compound observed on the mass chromatogram, the analyst can select this blob with the selection indicator. Instruct to select. Then, the library search unit extracts the spectrum data obtained at the time position where the indicated blob exists from the data obtained by performing the scan measurement with the comprehensive two-dimensional chromatograph mass spectrometer, By comparing the mass spectrum created based on the data with the mass spectrum stored in the spectrum library, compound information such as the compound name corresponding to the blob is obtained. Then, the compound information is displayed on the screen of the display unit. From this result, the analyst can confirm whether or not the quantitative result obtained from the peak area on the mass chromatogram is indeed the result of the target compound.

The second aspect of the chromatograph mass spectrometry data processing apparatus according to the present invention is as follows.
h) From the data obtained by performing the scan measurement with the comprehensive two-dimensional chromatograph mass spectrometer, the same mass to charge ratio or MRM transition as the mass chromatogram displayed on the screen of the display unit. It further includes a two-dimensional mass chromatogram creation unit that acquires data and creates a two-dimensional mass chromatogram based on the data,
The chromatogram display processing unit replaces the two-dimensional chromatogram created by the two-dimensional mass chromatogram creation unit with the two-dimensional chromatogram or together with the two-dimensional chromatogram and the mass chromatogram. It may be configured to display on the screen.

  According to this configuration, if there is only one blob on the two-dimensional mass chromatogram at the same position on the horizontal axis as the peak derived from the target compound observed on the mass chromatogram, the peak is truly It can be judged more reliably that it is derived only from the target compound.

  According to the chromatograph mass spectrometry data processing apparatus according to the present invention, the qualitative confirmation of a compound quantified based on data obtained by SIM measurement or MRM measurement is performed on the same sample with a comprehensive two-dimensional chromatograph mass spectrometer. It is possible to carry out with high accuracy using the result obtained. Comprehensive two-dimensional chromatographs have high separation performance, so when there are many contaminants in the sample, when performing multi-component simultaneous analysis of a large number of compounds in the sample, and further, the concentration of the target compound in the sample Even if it is low, it can be determined accurately whether there is no overlap of other compounds in the peak derived from the quantified target compound, thereby preventing erroneous quantification.

The schematic block diagram of one Example of the GC-MS system provided with the chromatograph mass spectrometry data processing apparatus which concerns on this invention. The flowchart which shows the characteristic data processing operation in the GC-MS system of a present Example. The figure which shows an example of the chromatogram display in the GC-MS system of a present Example. The figure which shows the other example of the chromatogram display in the GC-MS system of a present Example.

Hereinafter, an embodiment of a GC-MS system using a chromatograph mass spectrometry data processing apparatus according to the present invention will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of a GC-MS system according to the present embodiment.
The GC-MS system of the present embodiment has two measurement systems, a GC-MS measurement system 1 and a GC × GC-MS measurement system 2, in order to perform measurement on a sample.

  The GC-MS measurement system 1 includes a GC unit 11 including a column 112 and a sample introduction unit 111 including a sample vaporization chamber for introducing a sample gas into the column 112, and a mass spectrometry that is a quadrupole mass spectrometer or the like. And a device (MS unit) 12. The MS unit 12 performs MS / MS analysis such as a triple quadrupole mass spectrometer or a Q-TOF mass spectrometer in which the quadrupole mass filter at the subsequent stage of the mass spectrometer is replaced with a time-of-flight mass analyzer. May be a mass spectrometer capable of.

  The GC × GC-MS measurement system 2 has a constant component (compound) eluted from the primary column 212, a sample introduction part 211 including a sample vaporization chamber for introducing a sample gas into the primary column 212, and the like. A GC × GC unit 21 including a modulator 213 that collects at time (modulation time) intervals, and compresses and sends it out in time, and a secondary column 214 having a separation characteristic different from that of the primary column 212 and capable of high-speed separation. And a mass spectrometer (MS unit) 22 such as a quadrupole mass spectrometer. The MS unit 22 can also use a mass spectrometer capable of MS / MS analysis.

The measurement data obtained by the two measurement systems 1 and 2 are all input to the control / processing unit 3, and the control / processing unit 3 executes data processing as described later.
The control / processing unit 3 collects and stores data sequentially output from the measurement parameter setting unit 31, the analysis control unit 32, and the GC-MS measurement system 1 as time passes as functional blocks. The data storage unit 33, the GC × GC-MS measurement data storage unit 34 that collects and stores data sequentially output from the GC × GC-MS measurement system 2 over time, and the GC-MS measurement data storage unit 33 A mass chromatogram creation unit 35 that creates a mass chromatogram based on the stored data, a peak detection unit 36 that detects a peak in the mass chromatogram, and a GC × GC-MS measurement data storage unit 34 are stored. A two-dimensional chromatogram creation unit 37 for creating a two-dimensional chromatogram (total ion chromatogram) based on the data stored; A blob detection unit 38 for detecting a blob in the three-dimensional chromatogram, a quantitative calculation unit 39 for performing a quantitative calculation based on the area of the peak detected by the peak detection unit 36, and the time between the mass chromatogram and the two-dimensional chromatogram A chromatogram time axis adjustment unit 40 for adjusting the axis, a chromatogram display processing unit 41 for displaying the mass chromatogram and the two-dimensional chromatogram on which the time axis has been adjusted on the screen of the display unit 6, and the displayed two-dimensional A specific site designation processing unit 42 that accepts designation of an arbitrary blob on the chromatogram, a spectrum library 44 in which mass spectrum information is recorded corresponding to the compound information, and a compound by performing a search using the spectrum library 44 A library search unit 43 for identifying the two-dimensional mask roma at a specific mass-to-charge ratio Comprising a two-dimensional mass chromatogram creation unit 45 for creating grams, the. An input unit 5 operated by an analyst and a display unit 6 for presenting analysis results to the analyst are connected to the control / processing unit 3 as a user interface.

  The control / processing unit 3 usually uses a personal computer (or a higher performance workstation) as a hardware resource, and executes dedicated control / processing software installed in advance on the computer. Thus, each functional block is embodied.

In the GC-MS system of the present embodiment, characteristic operations and processing operations when quantifying a known compound contained in a sample (presumed to be contained) will be described with reference to the flowchart shown in FIG. To do.
The measurement parameter setting unit 31 displays a setting screen for inputting measurement parameters in the GC-MS measurement system 1 on the screen of the display unit 6, and the analyst views the measurement target compound from the input unit 5 while viewing the setting screen. Measurement parameters such as a measurement time range, a mass-to-charge ratio that is a target of SIM measurement in the measurement time range, and a separation condition in the GC unit 11 are input. In addition, the measurement parameter setting unit 31 displays a setting screen for inputting measurement parameters in the GC × GC-MS measurement system 2 on the screen of the display unit 6, and the analyst looks at this from the input unit 5. The measurement parameters such as the mass-to-charge ratio range of the scan measurement and the separation condition in the GC × GC unit 21 are input, and then the measurement start is instructed.

  In response to this instruction, the analysis control unit 32 operates each unit of the GC-MS measurement system 1 to perform measurement on the sample (step S1). That is, in the GC unit 11, the sample introduction unit 111 introduces the sample into the carrier gas supplied at a substantially constant flow rate. Various compounds contained in the sample are temporally separated while passing through the column 112 and introduced into the MS unit 12. The MS unit 12 selectively detects only ions having a predetermined mass-to-charge ratio within the set measurement time range. A detection signal from the MS unit 12 is converted into digital data at a predetermined sampling period by an A / D converter (not shown), input to the control / processing unit 3, and sequentially stored in the GC / MS measurement data storage unit 33.

  On the other hand, the analysis control unit 32 operates each part of the GC × GC-MS measurement system 2 and performs measurement on the same sample as the measurement target by the GC-MS measurement system 1 (step S2). That is, in the GC × GC unit 21, the sample introduction unit 211 introduces the sample into the carrier gas supplied at a substantially constant flow rate. Various compounds contained in the sample are separated to some extent in time while passing through the primary column 212. The modulator 213 repeats the operation of collecting all the compounds eluted from the primary column 212 during the modulation time, and compressing them to send them to the secondary column 214 with a very narrow bandwidth. The plurality of compounds sent at every modulation time are separated and eluted in the time direction with high resolution when passing through the secondary column 214, and are introduced into the MS unit 22 in the order of elution. The MS unit 22 performs scan measurement at an interval shorter than the time width during which one compound is eluted from the secondary column 214, and detects all compounds without omission. The detection signal from the MS unit 22 is converted into digital data at a predetermined sampling period by an A / D converter (not shown), input to the control / processing unit 3, and sequentially stored in the GC × GC-MS measurement data storage unit 34. The Although this measurement can be performed in parallel with the measurement by the GC-MS measurement system 1, it does not necessarily have to be performed in parallel.

  When the measurement is completed and the execution of quantitative analysis of the target compound is instructed in the state where the measurement data is stored in the measurement data storage units 33 and 34, the mass chromatogram creation unit 35 receives the GC-MS measurement data storage unit. Based on the data stored in 33, a mass chromatogram at a specific mass-to-charge ratio (m / z = M1) derived from the target compound is created (step S3). The peak detector 36 detects a peak near the retention time of the target compound on the mass chromatogram, calculates a peak area, and calculates a quantitative value based on the peak area (step S4).

  On the other hand, based on the data stored in the GC × GC-MS measurement data storage unit 34, the two-dimensional chromatogram creation unit 37 has the horizontal axis holding time of the primary column 212 and the vertical axis holding the secondary column 214. A two-dimensional chromatogram which is time and whose signal intensity is shown in color scale or gray scale is created (step S5). The two-dimensional chromatogram created here is not different from the two-dimensional chromatogram obtained by the conventional comprehensive two-dimensional GC.

  Usually, the separation conditions such as the rate of temperature rise in the GC section 11 of the GC-MS measurement system 1 are determined so that the component separation in the GC section 11 is optimal, and the GC × GC-GC of the GC × GC-MS measurement system 2 is determined. Separation conditions such as the temperature rise rate in the section 21 are determined so that the component separation through the primary column 212 and the secondary column 214 is optimal. Therefore, as described above, their separation conditions, particularly the heating rate, are different from each other, which leads to a difference in retention time for the same compound. Therefore, the chromatogram time axis adjustment unit 40 executes a process for correcting the difference in retention time of the same compound and adjusting the time axis between the mass chromatogram and the two-dimensional chromatogram (step S6).

Specifically, the time axis of the mass chromatogram and the two-dimensional chromatogram is adjusted as follows. If the column 112 in the GC unit 11 and the primary column 212 in the GC × GC unit 21 are of the same type or similar types, the time axis can be adjusted using the retention index. Therefore, here, a retention index of n-alkane which is often used for adjusting the time axis in the GC analysis is used. That is, the n-alkane is also measured at the time of each measurement by the GC-MS measurement system 1 and the GC × GC-MS measurement system 2 for the same sample. Then, the retention times in the measurement systems 1 and 2 are obtained from the measurement results, respectively, and the horizontal axis (time axis) of the mass chromatogram is converted into the retention index base using the known retention index of n-alkane, The horizontal axis (retention time axis of the primary column) of the two-dimensional chromatogram is also converted to the retention index base. That is, in both the mass chromatogram and the secondary chromatogram, the horizontal axis is the same retention index base, in other words, the time axis normalized by the retention index, and the two can be associated.
In the mass chromatogram, the barycentric position of the peak derived from n-alkane may be used as the retention time of the compound. In the two-dimensional chromatogram, the center of gravity of the blob derived from n-alkane is regarded as the retention time of the compound, and the retention time of the blob = the retention time of the primary column of the blob + the retention time of the secondary column of the blob. Thus, the holding time on the horizontal axis may be obtained.

  Since the horizontal axes of the mass chromatogram and the two-dimensional chromatogram are aligned in this way, the chromatogram display processing unit 41 creates an image in which the mass chromatogram and the two-dimensional chromatogram are arranged vertically with the horizontal axis in common. It displays on the screen of the display part 6 (step S7).

FIG. 3 shows a two-dimensional chromatogram obtained by performing a scan measurement of m / z = 40 to 510 in the GC × GC-MS measurement system 2, and a target with m / z = 65 in the GC-MS measurement system 1. This is an example in which a mass chromatogram obtained by SIM measurement is displayed side by side. The horizontal axis of both chromatograms is normalized by the retention index.
The peak of the lower mass chromatogram is used for quantification, and the blob observed on the upper two-dimensional chromatogram at the same horizontal axis as the peak indicates the qualitative information of the compound contained in the peak. . Therefore, when a plurality of blobs are observed in a vertical direction at a certain position on the horizontal axis, it means that a plurality of compounds respectively corresponding to the plurality of blobs are mixed at the same time. As a result, whether the peak used for the quantitative analysis on the mass chromatogram is derived from a single compound, or is it derived from a plurality of compounds, that is, whether another compound or impurities overlap, Can be determined.

  However, even if it can be confirmed that the peak used for the quantitative analysis on the mass chromatogram is derived from a single compound, the compound is not necessarily the target compound. Therefore, in this GC-MS system, any compound can be identified by the following procedure.

  That is, on the two-dimensional chromatogram displayed on the screen of the display unit 6 as described above, the analyst instructs the blob to be focused on by the input unit 5. For example, the blob may be clicked with a pointing device such as a mouse (step S8). Upon receiving this instruction, the specific part designation processing unit 42 recognizes the retention time of the instructed blob, reads out the mass spectrum data obtained at the retention time from the GC × GC-MS measurement data storage unit 34, and obtains the mass spectrum. Create (step S9). The library search unit 43 collates the peak pattern of the mass spectrum with the peak pattern of the mass spectrum recorded in the spectrum library 44, and searches for a compound having a mass spectrum with high similarity (step S10). If any compound can be identified, the identification result is displayed on the screen of the display unit 6, for example, the name of the identified compound at a position close to the designated blob (step S11).

  Thereby, the analyst can confirm whether or not the compound corresponding to the peak used for the quantitative calculation is certainly the target compound. In addition, when there is a possibility that a compound other than the target compound is mixed in the peak used for the quantitative calculation, it is also possible to confirm what the mixed compound is.

  In addition, in the display as illustrated in FIG. 3, it is possible to confirm the possibility that a compound other than the target compound is mixed in the peak used for the quantitative calculation, but the two-dimensional chromatogram is a total ion chromatogram. Therefore, it cannot be confirmed whether the compounds are indistinguishable from each other because they have the same mass-to-charge ratio, or are the compounds that can be distinguished because of the different mass-to-charge ratio. Therefore, in the GC-MS system of this embodiment, more accurate qualitative confirmation can be performed by the following procedure.

  When the analyst gives an instruction to create a two-dimensional mass chromatogram from the input unit 5 (step S12), the two-dimensional mass chromatogram creation unit 45 receives this instruction, and the mass of the mass chromatogram displayed at that time is displayed. Data corresponding to the charge ratio (m / z = M 1) is extracted from the GC × GC-MS measurement data storage unit 34. Then, a two-dimensional mass chromatogram with the time axis adjusted in step S6 is created (step S13). In this two-dimensional mass chromatogram, the horizontal axis and the vertical axis are the same as the two-dimensional chromatogram which is the total ion chromatogram displayed on the screen of the display unit 6, and the signal intensity is a specific mass-to-charge ratio ( The difference is the signal strength at m / z = M1). The chromatogram display processing unit 41 displays the two-dimensional mass chromatogram instead of the two-dimensional chromatogram displayed at that time (step S14). Alternatively, the two-dimensional mass chromatogram may be displayed in addition to the mass chromatogram and the two-dimensional chromatogram.

FIG. 4 shows an example in which a two-dimensional mass chromatogram of m / z = 65 is displayed instead of the two-dimensional chromatogram in FIG.
The two-dimensional mass chromatogram is a graph in which the mass chromatogram obtained by SIM measurement is further expanded in the vertical direction. From this two-dimensional mass chromatogram, peak A on the mass chromatogram is a mixture of two compounds, and peak C is a mixture of three compounds, which are peaks derived from a pure single compound. I understand that it is not. On the other hand, since peak B is derived from one compound, it can be seen that quantification using peak B is highly reliable.

  Of course, it is also possible to specify an arbitrary blob on the two-dimensional mass chromatogram instead of on the two-dimensional chromatogram, and perform a library search using a mass spectrum corresponding to the blob so that the compound identification can be performed. .

  As described above, in the GC-MS system of this example, the analyst can easily and accurately determine whether or not the peak on the mass chromatogram used for quantification of the target compound is derived from a single compound. Can be confirmed. Thereby, it is possible to avoid erroneous quantification using a peak in which impurities or the like overlap.

  In the above-described embodiment, the SIM measurement is performed by the MS unit 22 in the GC-MS measurement system 1. However, when the MS unit 22 is a mass spectrometer capable of MS / MS analysis, the quantitative performance is improved. Therefore, it is preferable to perform MRM measurement instead of SIM measurement. In that case, instead of a mass chromatogram at a specific mass-to-charge ratio, a mass chromatogram at a specific MRM transition may be created and displayed.

  Moreover, although the said Example applies this invention to GC-MS / MS system, it is clear that this invention is applicable to LC-MS system. In that case, another reference compound may be measured instead of n-alkane, and the time axis may be adjusted based on the retention time of the reference compound.

  Furthermore, the above-described embodiments and modifications are merely examples of the present invention, and it is obvious that modifications, corrections and additions as appropriate within the scope of the present invention are included in the scope of the claims of the present application.

DESCRIPTION OF SYMBOLS 1 ... GC-MS measurement system 11 ... GC part 111 ... Sample introduction part 112 ... Column 12 ... MS part 2 ... GC * GC-MS measurement system 21 ... GC * GC part 211 ... Sample introduction part 212 ... Primary column 213 ... Modulator 214 ... Secondary column 22 ... MS unit 3 ... Control / processing unit 31 ... Measurement parameter setting unit 32 ... Analysis control unit 33 ... GC-MS measurement data storage unit 34 ... GC × GC-MS measurement data storage unit 35 ... Mass Chromatogram creation section 36 ... peak detection section 37 ... two-dimensional chromatogram creation section 38 ... blob detection section 39 ... quantitative calculation section 40 ... chromatogram time axis adjustment section 41 ... chromatogram display processing section 42 ... specific site designation processing section 43 ... Library search unit 44 ... Spectrum library 45 ... Two-dimensional mass chromatogram creation unit 5 ... Input unit 6 ... Display unit

Claims (5)

a) Based on data obtained by performing selective ion monitoring (SIM) measurement or multiple reaction monitoring (MRM) measurement on a target sample with a chromatographic mass spectrometer, the mass at a mass-to-charge ratio corresponding to a specific compound is measured. A mass chromatogram creation section for creating a chromatogram;
b) Based on the data obtained by scanning the target sample with a comprehensive two-dimensional chromatograph mass spectrometer, the retention time in the first dimension column is orthogonal to the retention time in the second dimension column. A two-dimensional chromatogram creating unit for creating a two-dimensional chromatogram having two axes,
c) Adjust one or both of the time axes so that the appearance time of the same compound matches on the time axis of the mass chromatogram and the retention time axis of the first dimension column of the two-dimensional chromatogram. A time axis adjustment unit;
d) a chromatogram display processing unit that displays the mass chromatogram and the two-dimensional chromatogram, the time axis of which has been adjusted by the time axis adjustment unit, aligned on the screen of the display unit and displayed.
A chromatographic mass spectrometry data processing apparatus comprising: A chromatograph mass spectrometry data processing apparatus according to claim 1,
The time axis adjustment unit uses one of the mass chromatogram and the two-dimensional chromatogram using the results of measuring the reference compound by the chromatograph mass spectrometer and the comprehensive two-dimensional chromatograph mass spectrometer, respectively. Alternatively, a chromatograph mass spectrometry data processing apparatus characterized by adjusting both time axes. A chromatograph mass spectrometry data processing device according to claim 2,
The chromatograph mass spectrometer is a gas chromatograph mass spectrometer, the comprehensive two-dimensional chromatograph mass spectrometer is a comprehensive two-dimensional gas chromatograph mass spectrometer, and the reference compound is an n-alkane. Chromatographic mass spectrometry data processing device. The chromatograph mass spectrometry data processing device according to any one of claims 1 to 3,
e) a spectrum library in which mass spectrum information is stored in association with compound information;
f) a selection instruction unit for the analyzer to select and instruct an arbitrary blob on the two-dimensional chromatogram displayed on the screen of the display unit;
g) Acquire spectrum data obtained at the time position where the blob instructed by the selection instruction unit exists, and collate the mass spectrum created based on the data with the mass spectrum stored in the spectrum library A library search unit for obtaining compound information corresponding to the blob;
A chromatograph mass spectrometry data processing apparatus, further comprising: The chromatograph mass spectrometry data processing device according to any one of claims 1 to 3,
h) From the data obtained by performing the scan measurement with the comprehensive two-dimensional chromatograph mass spectrometer, the same mass to charge ratio or MRM transition as the mass chromatogram displayed on the screen of the display unit. It further includes a two-dimensional mass chromatogram creation unit that acquires data and creates a two-dimensional mass chromatogram based on the data,
The chromatogram display processing unit replaces the two-dimensional chromatogram created by the two-dimensional mass chromatogram creation unit with the two-dimensional chromatogram or together with the two-dimensional chromatogram and the mass chromatogram. A chromatograph mass spectrometry data processing apparatus characterized by being displayed on a screen.