Data processing method, information processing device, chromatograph-mass spectrometry device, and program

Abstract

To correct a measurement value of a target component in a sample by using a measurement result of a standard sample that does not contain the target component.SOLUTION: A data processing method corrects a measurement value of a target component in a target sample on the basis of a measurement value of a reference component included in a standard sample. The method includes: a step S12 of acquiring a feature quantity of the target component and the measurement value of the target component from a chromatogram obtained by analyzing the target sample; a step S14 of acquiring a feature quantity of the reference component and the measurement value of the reference component from a chromatogram obtained by analyzing the standard sample; and a step S16 of correcting the measurement value of the target component on the basis of the feature quantity of the target component, the feature quantity of the reference component, and the measurement value of the reference component.SELECTED DRAWING: Figure 10

Description

[Technical Field]

[0001] The present disclosure relates to a data processing method, an information processing device, a chromatographic mass spectrometer, and a program, and more particularly to data processing for correcting measurements obtained by an analytical device. [Background technology]

[0002] Measurement values ​​obtained by an analytical instrument may be affected not only by analytical conditions but also by the state of the instrument at the time of analysis. For example, in a chromatographic mass spectrometer, contamination of the mass spectrometer may affect measurement sensitivity. Therefore, even when the same sample is measured under the same analytical conditions, the measurement values ​​obtained before and after cleaning the mass spectrometer may differ. In other words, the measurement values ​​obtained by an analytical instrument contain errors due to differences in the timing of analysis.

[0003] As a method for correcting this error, Dunn, Warwick B., et al. "Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry," Nature protocols 6.7 (2011): 1060-1083. (Non-Patent Document 1) discloses a technique for correcting sample measurements based on the measurements of a pooled QC, which is a mixture of equal amounts of all samples. In Non-Patent Document 1, the pooled QC is analyzed between sample analyses. After the analysis, LOESS smoothing is performed using only the pooled QC measurements to calculate an approximate curve. The measurements of each sample are corrected based on the calculated approximate curve. This method is called QC-based robust LOESS signal correction (QC-RLSC) method. The pooled QC is a type of standard sample.

[0004] A pooled QC is created by mixing all samples in equal amounts. By mixing all samples in equal amounts, the amount of each component contained in the pooled QC is the average of the amounts of each component across all samples. The measured values ​​of the pooled QC approach the average of the sample measured values, preventing the pooled QC measured values ​​from being extremely different from the sample measured values. Furthermore, by mixing all samples to create a pooled QC, components contained in at least one of the samples are included in the pooled QC. Therefore, even if the component to be corrected is unknown at the start of the measurement, correction processing can be performed on the measured values ​​of that component after the measurement. [Prior art documents] [Non-patent literature]

[0005] [Non-Patent Document 1] Dunn, Warwick B., et al. "Procedures for large-scale metabolic profiling of serum and plasma using gas chromatography and liquid chromatography coupled to mass spectrometry." Nature protocols 6.7 (2011): 1060-1083. Summary of the Invention [Problem to be solved by the invention]

[0006] As in the method disclosed in Non-Patent Document 1, when a standard sample is prepared in advance and the measurement value of a sample is corrected based on the measurement value obtained by analyzing the standard sample, the component to be corrected must be contained in the standard sample. However, for example, if a new sample to be measured is added after the standard sample is prepared, the sample may contain a component that is not contained in the standard sample. In such a case, in order to correct the measurement value of the component, the user must prepare a new standard sample containing the component. Since the user must prepare a new standard sample, measurement costs may increase.

[0007] The present disclosure has been made in consideration of the above circumstances, and its purpose is to correct the measurement value of a specified component in a target sample by utilizing the results obtained by analyzing the standard sample when correcting the measurement value of a specified component not contained in the standard sample. [Means for solving the problem]

[0008] A data processing method according to a first aspect of the present disclosure is a data processing method for correcting a measurement value of a target component in a target sample obtained by an analytical device equipped with a mass spectrometer or a chromatographic mass spectrometer, using a standard sample containing a first reference component and a second reference component. For the target component, the first reference component, and the second reference component, the measurement value of each component is a value related to the amount of the corresponding component, and the feature amount of each component is the retention time and / or mass-to-charge ratio of the corresponding component. The data processing method includes the steps of: (1) acquiring a feature amount of a target component and a measurement value of the target component from a chromatogram obtained by analyzing a target sample under first analytical conditions at a first timing; (2) acquiring a feature amount of a first reference component, a feature amount of a second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing a standard sample under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing; and (3) correcting the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing.

[0009] An information processing device according to a second aspect of the present disclosure includes at least one processor and a memory accessible to the one or more processors. The memory stores one or more instructions to be executed by the processor. The processor executes the one or more instructions to acquire feature amounts and measurement values ​​of the target component from a chromatogram obtained by analyzing a target sample containing the target component under first analytical conditions at a first timing. The processor acquires feature amounts of the first reference component, feature amounts of the second reference component, measurement values ​​of the first reference component at each timing, and measurement values ​​of the second reference component at each timing from a chromatogram obtained by analyzing a standard sample containing the first reference component and the second reference component under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing. The processor corrects the measured value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measured value of the first reference component at each timing, and the measured value of the second reference component at each timing. For the target component, the first reference component, and the second reference component, the measured value of each component is a value related to the amount of the corresponding component, and the feature amount of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

[0010] A chromatography mass spectrometer according to a third aspect of the present disclosure includes a chromatograph unit, a mass analyzer unit, and a controller. The chromatograph unit temporally separates a target component contained in a target sample and a first reference component and a second reference component contained in a standard sample. The mass analyzer measures ions having mass-to-charge ratios derived from the target component, first reference component, and second reference component separated by the chromatograph unit. The controller acquires feature amounts and measured values ​​of the target component from a chromatogram obtained by analyzing the target sample under first analytical conditions at a first timing. The controller acquires feature amounts of the first reference component, feature amounts of the second reference component, and measured values ​​of the first reference component at each timing from a chromatogram obtained by analyzing the standard sample under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing. The controller corrects the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing. For the target component, the first reference component, and the second reference component, the measurement value of each component is a value related to the amount of the corresponding component, and the feature amount of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

[0011] A program according to a fourth aspect of the present disclosure is a program executed by a processor mounted on a computer. The computer acquires feature amounts of the target component and measurement values ​​of the target component from a chromatogram obtained by analyzing a target sample containing the target component under first analytical conditions at a first timing. The computer acquires feature amounts of the first reference component, feature amounts of the second reference component, measurement values ​​of the first reference component at each timing, and measurement values ​​of the second reference component at each timing from a chromatogram obtained by analyzing a standard sample containing a first reference component and a second reference component under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing. The computer corrects the measurement values ​​of the target component based on the feature amounts of the target component, feature amounts of the first reference component, feature amounts of the second reference component, measurement values ​​of the first reference component at each timing, and measurement values ​​of the second reference component at each timing. For the target component, the first reference component, and the second reference component, the measured value of each component is a value related to the amount of the corresponding component, and the feature value of each component is the retention time and / or mass-to-charge ratio of the corresponding component. [Effects of the Invention]

[0012] According to the data processing method of the present disclosure, the measurement value of a predetermined component in a target sample can be corrected using the analysis results of a standard sample that does not contain the predetermined component. [Brief explanation of the drawings]

[0013] [Figure 1] FIG. 1 is a schematic diagram of an analysis system according to an embodiment. [Figure 2] FIG. 10 is a diagram for explaining the procedure for creating a pooled QC. [Figure 3] FIG. 1 is a diagram illustrating pooled QC and the measurement order of samples. [Figure 4] FIG. 10 is a diagram for explaining a method for correcting the measured values ​​of a sample based on the measured values ​​of pooled QC in a comparative example. [Figure 5]FIG. 10 is a diagram for explaining the measurement order of samples. [Figure 6] FIG. 1 is a diagram showing an example of a chromatogram obtained by analyzing a sample. [Figure 7] FIG. 1 shows an example of a chromatogram of a standard sample analyzed in a different batch. [Figure 8] FIG. 10 shows an example of a chromatogram of a sample to be measured analyzed in different batches. [Figure 9] FIG. 10 is a diagram showing an example in which a target component of a target sample is corrected based on weights. [Figure 10] 10 is a flowchart showing data processing according to the embodiment. [Figure 11] 11 is a flowchart showing a subroutine of step S16 shown in FIG. DETAILED DESCRIPTION OF THE INVENTION

[0014] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. Hereinafter, a chromatograph mass spectrometer will be illustrated as an example of an analytical device, but the present invention is not limited to this and can be applied to analytical devices in general. Note that the same or corresponding parts in the drawings will be designated by the same reference numerals, and their description will not be repeated.

[0015] [Overall configuration of the analysis system] Fig. 1 is a block diagram showing the configuration of an analysis system 100 according to an embodiment. Referring to Fig. 1, analysis system 100 includes a processing device 10, an input device 20, a display device 30, and a chromatograph mass spectrometer 40. Analysis system 100 corrects errors in sample measurement values ​​acquired by chromatograph mass spectrometer 40 that are caused by differences in measurement timing. Note that processing device 10 may be incorporated into chromatograph mass spectrometer 40.

[0016] The processing device 10 includes a processor 11, a memory 12, and an input / output interface (I / F) 13. These components are connected to each other via a bus so that they can communicate with each other.

[0017] The processor 11 is an example of an electric circuit, and controls the operation of the processing device 10 by executing a given program. The program executed by the processor 11 may be stored in the memory 12, or may be stored in a storage device (not shown) external to the processing device 10. The processor 11 is, for example, a CPU (Central Processing Unit).

[0018] The memory 12 can store programs executed by the processor 11 and analytical data acquired by the chromatograph mass spectrometer 40 analyzing a sample. The analytical data includes, for example, a created chromatogram, created mass spectrum data, and component measurement values. The programs stored in the memory 12 include a correction program 121. The memory 12 includes volatile memory (e.g., RAM (Random Access Memory)) and non-volatile memory (e.g., ROM (Read Only Memory), a hard disk drive, and a solid state drive). The programs may also be stored in an external storage device accessible by the processor 11.

[0019] The input / output I / F 13 is an interface for exchanging various data between the processor 11 and devices connected to the input / output I / F 13. The input device 20, the display device 30, and the chromatograph mass spectrometer 40 are connected to the input / output I / F 13. The input / output I / F 13 is realized by, for example, a terminal block, a connector, and a network adapter. Data exchange via the input / output I / F 13 may be performed wirelessly, such as via Bluetooth (registered trademark) or wireless LAN, or may be performed wired using a Universal Serial Bus (USB) or the like. The processing device 10 can receive measurement values ​​acquired by devices other than the chromatograph mass spectrometer 40 via the input / output I / F 13 and perform data processing on the measurement values.

[0020] The input device 20 accepts information input from a user to the processing device 10. The information is, for example, the total number of samples, the type of sample, and the feature values ​​of the components. A detailed description of the feature values ​​of the components will be given later. The input device 20 is, for example, composed of a touch panel, a mouse, and a keyboard.

[0021] The display device 30 displays information in accordance with instructions from the processing device 10. The information may be, for example, a chromatogram of the sample, a mass spectrum of the components contained in the sample, measurement values ​​of the predetermined components before correction, and measurement values ​​of the predetermined components after correction. The display device 30 may be, for example, a liquid crystal display capable of displaying images.

[0022] The chromatographic mass spectrometer 40 analyzes a sample under predetermined analytical conditions and generates analytical data. The analytical conditions include, for example, the instrument used for the analysis, the column length, the type of column carrier, the column diameter, the column temperature, the type of solvent, and the solvent flow rate. The analytical data includes, for example, a chromatogram of the sample and mass spectrum data showing the mass distribution of ions derived from components contained in the sample. The analytical data is transmitted to the processing device 10. The processing device 10 extracts feature quantities and measurement values ​​of the components contained in the sample from the analytical data of the sample. The feature quantities of the components are values ​​related to the analytical conditions and the physicochemical properties of the components, such as retention time, mass-to-charge ratio, and mass-to-charge ratio of product ions. The measurement values ​​of the components are values ​​related to the amount of the components, such as the peak area and peak intensity of the components in the chromatogram. The chromatography mass spectrometer 40 is, for example, a liquid chromatography mass spectrometer, a gas chromatography mass spectrometer, a high performance liquid chromatography tandem mass spectrometer, or a gas chromatography tandem mass spectrometer.

[0023] [Comparative Example] In measurements using a chromatograph mass spectrometer, contamination can occur on the mass analyzer during repeated measurements, which can affect the analysis results. For example, even for the same sample, measurements taken on different days may not match. In other words, measurements obtained using a chromatograph mass spectrometer may contain errors due to differences in the state of the analyzer caused by differences in the timing of measurements, even if the analysis conditions are the same.

[0024] One known method for correcting the above-mentioned errors is a technique for correcting sample measurements based on the measurement values ​​of a standard sample, known as a pooled QC, as described in Non-Patent Document 1. Figure 2 illustrates the procedure for creating a pooled QC. Assume that there are N samples to be measured. As shown in Figure 2, the pooled QC is created by mixing all samples in equal amounts. By mixing all samples in equal amounts, the amount of each component contained in the pooled QC is the average of all samples for that component. In other words, the measurement value of the pooled QC approaches the average of the sample measurements, preventing the measurement value of the pooled QC from being extremely different from the sample measurements. Furthermore, by mixing all samples to create a pooled QC, components contained in at least one sample are included in the pooled QC. Therefore, even if the component to be corrected is unknown at the start of the analysis, correction processing can be performed on the measurement value of that component after the analysis is completed. The created pooled QC is dispensed into an appropriate number of aliquots. In Figure 2, the created pooled QC is divided into M aliquots.

[0025] The chromatograph mass spectrometer analyzes the pooled QC before and after sample analysis, sequentially obtaining sample and pooled QC measurements. Figure 3 illustrates the pooled QC and sample measurement sequence. In Figure 3, the white containers represent the samples to be measured, and the gray containers represent the pooled QC. The operator prepares one pooled QC by dividing an equal amount of solution from each of the 36 samples. The prepared pooled QC is then divided into appropriate portions and measured at appropriate times before or after the sample analysis. For example, as shown in Figure 3, the chromatograph mass spectrometer analyzes the pooled QC twice consecutively before the start of sample analysis, and then analyzes the pooled QC once for every four samples. After the last sample is analyzed, the pooled QC is analyzed twice consecutively.

[0026] As a result of the series of analyses performed as described above, sample measurement values ​​and pooled QC measurement values ​​are obtained sequentially. The processing device 10 corrects the sample measurement values ​​based on the pooled QC measurement values. FIG. 4 is a diagram illustrating a method for correcting the sample measurement values ​​based on the pooled QC measurement values. The graph shown at the top of FIG. 4 shows the measurement values ​​obtained in the order in which the samples and pooled QC were analyzed. White circles indicate sample measurement values, and gray circles indicate pooled QC measurement values. Here, for example, the measurement value of the 10th analyzed sample, indicated by point P1, is greater than the measurement value of the 21st analyzed sample, indicated by point P2.

[0027] Ideally, the measurement values ​​of the pooled QCs should be equal regardless of the timing of analysis. Therefore, to correct the measurement values ​​of the samples, LOESS smoothing is performed only on the measurement values ​​of the pooled QCs, and an approximate curve L1 is calculated. The measurement values ​​of each sample are corrected based on the calculated approximate curve L1. The graph shown at the bottom of Figure 4 shows the relative measurement values ​​of the samples after correction. Note that the relative measurement values ​​in this graph are normalized values ​​where the value indicated by the approximate curve L1 is set to 1. In the graph shown at the bottom of Figure 4, the measurement values ​​of the pooled QCs have been corrected so that they are approximately constant.

[0028] Point P3 indicates the corrected measurement value of the 10th sample analyzed, and point P4 indicates the corrected measurement value of the 21st sample analyzed. Before correction, point P1 was larger than point P2, but after correction, point P3 is smaller than point P4. In this way, by using the QC-RLSC method, errors contained in each measurement value due to differences in analysis timing can be corrected, improving measurement accuracy.

[0029] In a correction method using the measured values ​​of a standard sample, such as a pooled QC, the measured values ​​of a specific component of a target sample are corrected based on the measured values ​​of the specific component of the standard sample. For example, in the measured values ​​of a chromatograph mass spectrometer, the detection sensitivity and ionization efficiency of components A and B may differ. In other words, the error in the measured value of component A due to differences in the timing of analysis may differ from the error in the measured value of component B due to differences in the timing of analysis. Therefore, if the error in the measured value of component B is corrected based on the error in the measured value of component A, the accuracy of the corrected measured value of component B may be insufficient. Therefore, it is desirable that the standard sample contain the component to be corrected.

[0030] However, for example, if a new sample to be analyzed is added after a standard sample has been prepared, the component to be corrected may not be contained in the standard sample. Furthermore, in the QC-RLSC method described above, the amount of a component contained in a trace amount in some samples is very small in the pooled QC. Therefore, in the measurement of the pooled QC, the component may be below the detection limit, and a measurement value of the component in the pooled QC may not be obtained.

[0031] [Data processing method according to the embodiment] Therefore, in the data processing method according to the present embodiment, the variation rate of the target component is estimated based on the variation rates of the measured values ​​of two or more reference components contained in the standard sample. According to this data processing method, even if the standard sample does not contain the target component, the user can correct the measured value of the target component in the target sample.

[0032] In the data processing method according to the present embodiment, when estimating the variation rate of a predetermined component, a degree of influence (weight) calculated based on the feature amount of the predetermined component and the feature amount of the reference component is assigned to the reference component of the standard sample. By placing emphasis on the variation rate of the reference component having similar features to the predetermined component, it is possible to improve the accuracy of estimating the variation rate of the predetermined component.

[0033] FIG. 5 is a diagram illustrating a sample to be analyzed by the chromatograph mass spectrometer 40. In FIG. 5, the sample to be measured is shown in a white container, and the standard sample is shown in a black container. The sample to be measured contains a predetermined component. The standard sample contains two or more reference components, but does not contain the predetermined component.

[0034] Assume that five analyses are performed in one analysis group, and that one analysis group is called a batch. At least within the same batch, samples are analyzed under the same analytical conditions. Analyses within the same batch are performed consecutively, and it is assumed that there is no error due to differences in measurement timing between analyses within the same batch. Therefore, the measurement value of sample Y belonging to batch 2 will contain an error due to the difference in analysis timing compared to the measurement value of sample X belonging to batch 1.

[0035] In one batch, a standard sample is analyzed once, followed by four consecutive analyses of the target sample. Therefore, when one batch is analyzed, the processing device 10 acquires the measurement values ​​of two or more reference components contained in the standard sample, as well as the measurement values ​​of a predetermined component in each sample. The data processing according to this embodiment is used, for example, when comparing the measurement values ​​of a predetermined component in sample X belonging to batch 1 with the measurement values ​​of a predetermined component in sample Y belonging to batch 2. The following describes the process of correcting errors in measurement values ​​due to differences in batches.

[0036] <1. Sample analysis using a chromatography mass spectrometer> As described above, the standard sample and the target sample are sequentially analyzed by the chromatograph mass spectrometer 40. The chromatograph mass spectrometer 40 measures the standard sample and the target sample and creates a chromatogram for each sample. The chromatograms created are a chromatogram showing the relationship between the detection intensity and retention time of ions for each mass-to-charge ratio, and a total ion chromatogram showing the relationship between the detection intensity and retention time of all ions introduced into the chromatograph mass spectrometer 40. Furthermore, the chromatograph mass spectrometer 40 detects product ions by defining ions whose detection intensity in the chromatogram for each mass-to-charge ratio is equal to or greater than a predetermined value as precursor ions. The measurement data acquired by the chromatograph mass spectrometer 40 includes the chromatogram showing the relationship between the detection intensity and retention time of ions for each mass-to-charge ratio, the total ion chromatogram, and the mass-to-charge ratios of the product ions when ions whose detection intensity is equal to or greater than a predetermined value are defined as precursor ions.

[0037] <2. Feature extraction> The processing device 10 automatically recognizes peaks on the chromatogram and extracts the feature quantity of each peak from the analysis data acquired by the chromatograph mass spectrometer 40.

[0038] The processing device 10 identifies peaks of each component contained in the sample in the total ion chromatogram for each sample created by the chromatograph mass spectrometer 40. The mass-to-charge ratio of the ions corresponding to the retention time of each identified peak is derived from the chromatogram created for each mass-to-charge ratio. In this embodiment, for example, the average or median of the mass-to-charge ratios of the ions detected at the retention time corresponding to a peak recognized in the total ion chromatogram is used as the mass-to-charge ratio of that peak. Furthermore, the processing device 10 acquires, as a feature, the mass-to-charge ratio of the product ions obtained by the chromatograph mass spectrometer 40 using ions having the specified mass-to-charge ratio as precursor ions.

[0039] Alternatively, the user may input features for identifying the predetermined component to be corrected and features for identifying the reference component that serves as the basis for correction to the input device 20. In this case, the processing device 10 accepts the features input by the user and identifies peaks having the features from the chromatogram. The processing device 10 uses the identified peaks as peaks derived from the predetermined component and the reference component in subsequent processing.

[0040] 6 is a diagram showing an example of a total ion chromatogram created by analyzing a standard sample and a sample to be measured by the chromatograph mass spectrometer 40. The process by which the processing device 10 acquires the feature quantities and measurement values ​​of each peak from the chromatogram will be described with reference to FIG.

[0041] First, the processing device 10 recognizes peaks in the chromatogram created by the chromatograph mass spectrometer 40 analyzing the standard sample in batch 1. The processing device 10 recognizes peaks in the chromatogram created by the chromatograph mass spectrometer 40 analyzing the standard sample in batch 1. A The peak with retention time RT B As shown in FIG. 6, a peak has a width on a chromatogram. In this embodiment, the retention time of a peak is the time of the peak's apex, but this is not limited thereto. For example, the retention time may be the start point or end point of the peak. Here, if the retention time is RT A The peak at RT is due to component A and has a retention time of RT B The peak at is determined to be due to component B.

[0042] Next, based on the chromatogram (not shown) for each mass-to-charge ratio created by the chromatograph mass spectrometer 40, the retention time is determined as RT A Component A and its retention time are RT BThe mass-to-charge ratio mz1 of each of the components B is determined. Furthermore, the mass-to-charge ratio mz2 of the product ions when these components are used as precursor ions is obtained from the analysis data of the chromatographic mass spectrometer 40. Note that product ions of 1 or more are generally detected. In this embodiment, the chromatographic mass spectrometer 40 analyzes the corresponding components as precursor ions, and the mass-to-charge ratio of the ion with the highest detection intensity among the detected product ions is used as mz2. The values ​​of mz1 and mz2 obtained by the processing device 10 are shown in box Z in FIG. 6.

[0043] The processing device 10 also calculates the peak area, which is the area of ​​the region surrounded by each peak and a line segment drawn from the start point of the peak to the end point of the peak. The area of ​​a peak is proportional to the amount of the component. In other words, the peak area can be considered a measurement value. The highest detected intensity value for the target peak may also be used as the measurement value of the component that formed the peak.

[0044] In Figure 6, the processing device 10 calculates that the area of ​​the peak derived from component A in the standard sample of batch 1 is 2, and the area of ​​the peak derived from component B in the standard sample of batch 1 is 3. In Figure 6, the area value of each peak is shown at the apex of the corresponding peak.

[0045] The processing device 10 performs the above-described processing on each of the chromatograms of sample X of batch 1, the standard sample of batch 2, and sample Y of batch 2 created by the chromatograph mass spectrometer 40, and obtains the feature quantities and measurement values ​​of each component contained in each sample. As shown in FIG. 6, from the chromatogram of sample X, the processing device 10 obtains the retention time RT C , mz1, mz2, and measurement values. The processing device 10 also obtains measurement values ​​of components A and B in batch 2 from the standard sample of batch 2. The processing device 10 also obtains measurement values ​​of component C of sample Y from the chromatogram of sample Y.

[0046] The processing device 10 sets components A and B contained in the standard sample as reference components. The processing device 10 also sets component C, which is not contained in the standard sample but is contained in sample X and sample Y, as a predetermined component.

[0047] Note that feature values ​​can change depending on the analysis conditions. Therefore, the feature values ​​of component A in batch 1 may not match the feature values ​​of component A in batch 2. In such cases, the feature values ​​of component A in subsequent processing may be the average of the feature values ​​of component A in batch 1 and the feature values ​​of component A in batch 2, or may be either the feature values ​​of component A in batch 1 or batch 2.

[0048] <3. Weighting of reference components relative to specified components> The weight indicating the degree of influence of each reference component on the predetermined component is calculated based on the feature of each reference component and the feature of the predetermined component. The processing device 10 assigns a greater weight to a reference component, among two or more reference components, whose common feature value is closer to the value of the common feature of the predetermined component. For example, if a standard sample contains a first reference component and a second reference component, and the difference between the value of the common feature of the first reference component and the value of the common feature of the predetermined component is smaller than the difference between the value of the common feature of the second reference component and the value of the common feature of the predetermined component, a greater weight is assigned to the first reference component. In this case, the value of the common feature of the first reference component is closer to that of the common feature of the predetermined component than that of the second reference component. The similarity between the feature values ​​of each reference component and the predetermined component is not limited to comparison based on difference. For example, if the quotient obtained by dividing the value of a predetermined feature of a first reference component by the value of the feature of the predetermined component is closer to 1 than the quotient obtained by dividing the value of the feature of the second reference component by the value of the feature of the predetermined component, the first reference component may be deemed to have a closer value of the feature common to the predetermined component than the second reference component.

[0049] In Figure 6, focusing on retention time, RT A <RT B <RT CThat is, when the retention time is used as an index, it can be said that component A is a component having a feature quantity more similar to component C than to component B. Therefore, the processing device 10 calculates the weights such that component B is weighted more heavily than component A in the element of retention time.

[0050] Furthermore, in FIG. 6, focusing on mz1, the value of mz1 of component C is closer to that of mz1 of component A than to that of mz1 of component B. In other words, when mz1 is used as an index, it can be said that component B is a component having a feature quantity more similar to that of component C than that of component A. Therefore, the processing device 10 calculates weights for the elements of mz1 so that component A is weighted more than component B. Also, when mz2 is used as an index, the processing device 10 calculates weights so that component A is weighted more than component B, just as when mz1 is used as an index.

[0051] The weight of the reference component is calculated for each reference component using the retention time, mz1, and mz2. Specifically, for example, when the retention time, mz1, and mz2 are used as feature quantities and a Gaussian function is used, the weight of the reference component with respect to the target component is determined by the following formula (1).

[0052]

number

[0053] In equation (1), the retention time of the target component is RT T The retention time of the reference component is RT Q The target component mz1 is mz1 T Let mz1 of the reference component be mz1 Q and the target component mz2 is mz2 T Let mz2 of the reference component be mz2 Q Let σRT, σmz1, σmz2, and C be predetermined numbers.

[0054] σRT, σmz1, and σmz2 are numbers for adjusting the weights. By setting these numbers, the user can adjust the degree of influence of each feature on the determination of the weights of the reference components. As shown in equation (1), for example, when the value of σRT is increased in determining the weights of the reference components, the degree of influence of retention time increases. By adjusting the values ​​of σRT, σmz1, and σmz2, the user can adjust the influence of each feature on the determination of the weight.

[0055] Furthermore, C is a constant greater than 0, which prevents the weight from becoming zero when there is a large difference between the feature amount of the predetermined component and the feature amount of the reference component.

[0056] In calculating the weight of the reference component, a Gaussian function is used in equation (1), but the use of the Gaussian function is not limited thereto, and a Cauchy function or a T distribution may also be used.

[0057] For example, when the Cauchy function is used, the weight of the reference component is determined by the following equation (2).

[0058]

number

[0059] In equation (2), the retention time of the target component is RT T The retention time of the reference component is RT Q The mass-to-charge ratio of the target component is mz1 T and the mass-to-charge ratio of the reference component is mz1 Q and the target component mz2 is mz2 T Let mz2 of the reference component be mz2 Q Let σRT, σmz1, σmz2, and C be predetermined numbers.

[0060] The user can select a function to be used in the weighting process of the reference component in accordance with the characteristics of the predetermined component.

[0061] <4. Determination of weighting coefficients for reference components based on weighting> Based on the calculated weight for each reference component, the processing device 10 determines a weighting factor for each reference component. The weighting factor is determined, for example, based on the ratio of the weights. In FIG. 6, the weight of component A relative to component C is expressed as W A The weight of component B relative to component C is W B Then, the weighting coefficient F of component A A is W A / W A +W B The weighting coefficient F of component B B is W B / W A +W B It should be noted that the method for determining the weighting coefficients is not limited to the above-described method.

[0062] <5. Calculation of the variation rate of the reference component> Next, the variation rate of the reference component between batches is calculated. FIG. 7 is a diagram for explaining the variation rate of the reference component. In FIG. 7, chromatograms of standard samples obtained in different batches are shown overlapping each other. The chromatogram obtained in batch 1 is shown by a solid line, and the chromatogram obtained in batch 2 is shown by a dotted line. The standard sample has a retention time of RT A Component A has a retention time of RT B The standard sample contains component B, which has a retention time of RT C It does not contain component C, which is

[0063] As shown in the chromatogram in Figure 7, the peak areas of component A and component B are different in batch 1 and batch 2, even though the same standard sample was analyzed. For example, if the measured value of component A in batch 1 is α1 and the measured value of component A in batch 2 is α2, the variability V of the measured value of component A in batch 2 relative to batch 1 is A Similarly, if the measured value of component B in batch 1 is β1 and the measured value of component B in batch 2 is β2, the rate of variation V of the measured value of component B in batch 2 relative to batch 1 is B becomes β2 / β1.

[0064] 6. Estimating the batch-to-batch variability of a given component A method for estimating the variability of a specific component using the weighting coefficient and variability of the reference component will be described below. The variability of a specific component corresponds to the measured value of component C in batch 2 when the standard sample contains component C and the measured value of component C in batch 1 is 1.

[0065] The variability of a predetermined component is, for example, the sum of the weight coefficients of each reference component multiplied by the variability of the corresponding reference component. Specifically, in FIG. 6, the variability V of component C of batch 2 relative to batch 1 is C is the weighting coefficient of component A, A The fluctuation rate of component A is V A and the weighting coefficient of component B is F B The fluctuation rate of component B is V B Then, V C =F A V A +F B V B It is expressed as:

[0066] 7. Correction of batch-to-batch measurements of specific components Based on the estimated fluctuation rate of the predetermined component, the measured values ​​acquired in different batches are corrected. Figure 8 is a diagram for explaining a method for correcting the measured values ​​of the predetermined component based on the estimated fluctuation rate of the predetermined component.

[0067] FIG. 8 shows chromatograms generated by the chromatograph mass spectrometer 40 after analyzing samples X and Y. As shown in FIG. 8, the measured value of component C in sample X in batch 1 is γ1, and the measured value of component C in sample Y in batch 2 is γ2. Measurement values ​​obtained in different batches contain errors due to differences in the timing of the analyses. Therefore, when comparing the amount of component C contained in sample X with the amount of component C contained in sample Y, γ1 and γ2 cannot be simply compared. Therefore, it is necessary to estimate the measurement value that would be obtained if sample X were analyzed in batch 2.

[0068] Therefore, the processing device 10 multiplies the measured value γ1 of the component C of the sample X by the estimated fluctuation rate V of the component C. C to obtain the corrected measurement value γ3 of component C of sample X. In other words, the corrected measurement value γ3 of component C of sample X is γ3 = γ1V C This becomes:

[0069] When comparing the amount of component C contained in sample X with the amount of component C contained in sample Y, as shown in Figure 8, the measured value of component C in sample X is multiplied by the fluctuation rate V C The user needs to compare γ3 obtained by multiplying with γ2.

[0070] The estimated fluctuation rate of the predetermined component is used as a correction coefficient to be used when correcting the measured value.

[0071] In the above example, the difference between the feature amount of the reference component and the feature amount of the predetermined component is used to determine the weight, but the ratio between the feature amount of the reference component and the feature amount of the predetermined component may also be used. The ratio between the feature amount of the reference component and the feature amount of the predetermined component corresponds to the difference between the logarithms of the respective feature amounts.

[0072] In the above example, the data processing according to this embodiment was applied to the correction of measurement values ​​in the analysis of samples between batches, but it may also be applied to the correction of measurement values ​​in the analysis of samples within a batch. For example, as in the example shown in Figure 3, in data obtained by sequentially measuring a sample and a pooled QC, this data processing may be used to correct the measurement value of a specific component in the sample based on the measurement value of a reference component contained in the pooled QC. In this case, it is desirable that the analysis conditions for each sample are the same.

[0073] Figure 9 shows an example of the results of correction using the data processing method. The amount of metabolites in human plasma was measured using liquid chromatography tandem mass spectrometry. The measured values ​​of the metabolites were corrected using a specific substance in the plasma as a reference component. Figure 9 shows the coefficient of variation of the measured values ​​of each metabolite. White indicates the coefficient of variation of the measured values ​​of each metabolite before correction, and black indicates the coefficient of variation of the measured values ​​of each metabolite after correction. The coefficient of variation is a value that represents the variability of the data; a smaller coefficient of variation indicates less variability in the data. Figure 9 shows that correction increases the number of metabolites with coefficients of variation greater than or equal to 0.0 and less than 0.0070. In other words, it is estimated that performing the above-described correction reduces measurement errors due to differences in the timing of analysis, thereby reducing data variability.

[0074] [Data processing flow] 10 is a flowchart showing an example of data processing of measurement values ​​obtained by analyzing a sample with the chromatographic mass spectrometer 40. In one implementation example, the data processing subroutine of FIG. 10 is called from the main routine and executed when the processor of the processing device 10 executes the correction program 121. The processing device 10 can be considered an example of an information processing device. The standard sample contains a first reference component and a second reference component, and the target sample to be measured contains a target component.

[0075] The following flowchart describes the process of correcting the measurement values ​​of the target components of the target samples when a standard sample is analyzed by the chromatographic mass spectrometer 40 in each of batch 1 and batch 2, and a target sample is analyzed by the chromatographic mass spectrometer 40 in batch 2.

[0076] In step S10, the processing device 10 receives chromatograms of the standard samples and the target samples in each of the different batches analyzed by the chromatograph mass spectrometer 40.

[0077] In step S12, the processing device 10 acquires feature quantities of the first reference component, feature quantities of the second reference component, measurement values ​​of the first reference component in each batch, and measurement values ​​of the second reference component in each batch. The feature quantities may be extracted by the processing device 10 from the chromatogram received in step S10, or may be input by the user to the input device 20. The feature quantities may be, for example, the retention time of the component when subjected to chromatography, the mass-to-charge ratio of the component, and the mass-to-charge ratio of the product ion when the component is used as a precursor ion. The measurement values ​​may be, for example, the peak area of ​​the component on the chromatogram. Note that in the following steps, the E target components are processed one by one.

[0078] In step S14, the processing device 10 acquires the feature amount and measurement value of one of the E target components from the chromatogram received in step S10.

[0079] In step S16, the processing device 10 corrects the measurement value of the target component using the feature amounts of the first and second reference components, the measurement values ​​of the first and second reference components in each batch, and the measurement values ​​of the second reference component in each batch, all obtained in step S12. The correction processing subroutine of step S16 is shown in FIG.

[0080] Referring to FIG. 11, in step S20, the processing device 10 calculates the influence of the first reference component on the target component using the feature amount of the target component and the feature amount of the first reference component.

[0081] In step S22, the processing device 10 calculates the influence of the second reference component on the target component using the feature amount of the target component and the feature amount of the second reference component.

[0082] In step S24, the processing device 10 calculates a correction coefficient for the target component using the influence of the first reference component calculated in step S20 and the influence of the second reference component calculated in step S22.

[0083] In step S26, the processing device 10 multiplies the measurement value of the target component by the correction coefficient for the target component. Thereafter, the processing device 10 ends the correction processing subroutine and returns control to FIG.

[0084] 10, in step S18, the processing device 10 determines whether or not the processing of the E target components received in step S12 has been completed. If the processing of all target components has been completed (YES in step S18), the processing device 10 ends the data processing subroutine and returns the processing to the main routine; otherwise (NO in step S18), the processing device 10 returns the processing to step S14.

[0085] In the above-described data processing, when a standard sample does not contain a component to be corrected, the measurement value of the component to be corrected can be corrected based on the measurement value of a reference component contained in the standard sample. Therefore, when a sample containing a predetermined component that is not contained in the standard sample is analyzed after preparing the standard sample, the cost of preparing a new standard sample can be reduced.

[0086] In the data processing described above, the weights of the reference components included in the standard components are determined based on information obtained by analyzing the reference components and the components to be corrected. Therefore, the data processing method can be applied even when the components to be corrected are unknown and their chemical properties are unknown.

[0087] The above-described data processing method can be used, for example, in food analysis. For example, consider the case of measuring the amount of components contained in genetically modified vegetables. Genetically modified vegetables may contain components that differ from the vegetables before genetic modification due to the genetic modification. In such cases, a standard sample containing representative components contained in the target vegetables can be prepared, and the measured values ​​of the components contained in the genetically modified vegetables can be corrected based on the measured values ​​of the standard sample. By using this data processing method, even if the analyst cannot predict the components contained in the genetically modified vegetables, the measured values ​​of the components contained in each vegetable can be corrected.

[0088] The data processing method described above can also be used, for example, when analyzing additives contained in imported materials. For example, when pulp is imported, the additives contained in the pulp may vary depending on the country of origin and the time of import. Therefore, a standard sample containing representative components contained in pulp can be prepared, and the measured values ​​of the additives contained in each pulp can be corrected based on the measured values ​​of the standard sample. By using this data processing method, the measured values ​​of the additives contained in each pulp can be corrected even if the additives contained in the pulp are unknown before the measurement.

[0089] [Aspect] It will be appreciated by those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0090] (Item 1) A data processing method according to one embodiment corrects a measurement value of a target component in a target sample obtained by an analytical device equipped with a mass spectrometer or a chromatographic mass spectrometer using a standard sample containing a first reference component and a second reference component. For the target component, the first reference component, and the second reference component, the measurement value of each component is a value related to the amount of the corresponding component, and the feature amount of each component is the retention time and / or the mass-to-charge ratio of the corresponding component. The data processing method includes the steps of: acquiring feature amounts of the target component and measured values ​​of the target component from a chromatogram obtained by analyzing the target sample under first analytical conditions at a first timing; and acquiring feature amounts of the first reference component, feature amounts of the second reference component, measured values ​​of the first reference component at each timing, and measured values ​​of the second reference component at each timing from a chromatogram obtained by analyzing the standard sample under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under second analytical conditions at a third timing. The data processing method also includes the step of correcting the measured values ​​of the target component based on the feature amounts of the target component, feature amounts of the first reference component, feature amounts of the second reference component, measured values ​​of the first reference component at each timing, and measured values ​​of the second reference component at each timing.

[0091] According to the data processing method described in paragraph 1, the measurement value of the target component in the sample can be corrected using the results obtained by analyzing a standard sample that does not contain the target component.

[0092] (Clause 2) In the data processing method described in paragraph 1, the correcting step may include the steps of: calculating an influence of the first reference component using a feature amount of the target component and a feature amount of the first reference component; and calculating an influence of the second reference component using the feature amount of the target component and a feature amount of the second reference component. The correcting step may include the steps of calculating a correction coefficient for the target component based on the measurement value of the first reference component at each timing, the measurement value of the second reference component at each timing, and the influence of the first reference component and the influence of the second reference component; and multiplying the measurement value of the target component by the correction coefficient.

[0093] According to the data processing method described in paragraph 2, the influence of a reference component on a target component is calculated based on the feature amount of the target component and the feature amount of the reference component. Then, a correction coefficient for the target component is calculated according to the magnitude of the influence of the reference component. This allows the user to correct the measurement value of the target component according to the influence of the reference component on the target component.

[0094] (Item 3) In the data processing method described in item 1 or 2, the second analysis conditions may be the same as the first analysis conditions.

[0095] According to the data processing method described in paragraph 3, the measured value of the target component of the target sample is corrected based on the analytical data of the target sample and the standard sample obtained under the same analytical conditions.

[0096] (4) In the data processing method described in any one of paragraphs 1 to 3, the feature amount of the target component, the feature amount of the first reference component, and the feature amount of the second reference component may include at least one of the retention time, mass-to-charge ratio, and mass-to-charge ratio of the corresponding component, and the mass-to-charge ratio of the product ion.

[0097] According to the data processing method described in paragraph 4, the measurement value of the target component is corrected using at least one of the retention times, mass-to-charge ratios, and mass-to-charge ratios of the reference component and target component, and the product ion mass-to-charge ratios.

[0098] (Item 5) In the data processing method described in any one of Items 1 to 4, the measurement value of the target component, the measurement value of the first reference component, and the measurement value of the second reference component may be calculated based on at least one of a peak area and a peak intensity in a chromatogram of the corresponding component.

[0099] According to the data processing method described in item 5, the measured value of a component is calculated based on at least one of the peak area and the peak intensity in the chromatogram.

[0100] (Clause 6) In the data processing method described in clause 2, the step of calculating the influence of the first reference component and the step of calculating the influence of the second reference component may each determine the corresponding weight using at least one of a multidimensional Gaussian distribution and a multidimensional Cauchy distribution function.

[0101] According to the data processing method described in Section 6, the influence of the reference component is determined using at least one of a multidimensional Gaussian distribution function and a multidimensional Cauchy distribution function.

[0102] (Clause 7) In the data processing method described in clause 2, in each of the steps of calculating the influence of the first reference component and calculating the influence of the second reference component, the smaller the difference between the feature amounts of the target component and the corresponding reference component, the larger the corresponding influence.

[0103] According to the data processing method described in paragraph 7, the smaller the difference between the feature value of the target component and the feature value of the reference component, the more weight is assigned to the measurement value of the reference component.

[0104] (Item 8) In the data processing method described in Item 2, the step of calculating the influence of the first reference component and the step of calculating the influence of the second reference component each include calculating the retention time of the target component as RT T and the retention time of the corresponding reference component is RT Q and the mass-to-charge ratio of the target component is mz1 T and the mass-to-charge ratio of the corresponding reference component is mz1 Q and the mass-to-charge ratio of the product ion of the target component is mz2 T and the mass-to-charge ratio of the product ion of the corresponding reference component is mz2 Q When σRT, σmz1, σmz2 and C are predetermined numbers, the corresponding influence degree may be calculated by the formula (3).

[0105]

number

[0106] (Item 9) In the data processing method described in Item 2, the step of calculating the influence of the first reference component and the step of calculating the influence of the second reference component each include calculating the retention time of the target component as RT T and the retention time of the corresponding reference component is RT Q and the mass-to-charge ratio of the target component is mz1 T and the mass-to-charge ratio of the corresponding reference component is mz1 Q and the mass-to-charge ratio of the product ion of the target component is mz2 T and the mass-to-charge ratio of the product ion of the corresponding reference component is mz2 Q When σRT, σmz1, σmz2, and C are predetermined numbers, the corresponding influence degree may be calculated by the formula (4).

[0107]

number

[0108] (Clause 10) An information processing device according to one aspect includes at least one processor and a memory accessible to the one or more processors, the memory storing one or more instructions to be executed by the processor. By executing the one or more instructions, the processor acquires a feature amount of the target component and a measurement value of the target component from a chromatogram obtained by analyzing a target sample containing the target component under first analytical conditions at a first timing; acquires a feature amount of the first reference component, a feature amount of the second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing a standard sample containing a first reference component and a second reference component under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under second analytical conditions at a third timing; and corrects the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing. For the target component, the first reference component, and the second reference component, the measured value of each component is a value related to the amount of the corresponding component, and the feature amount of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

[0109] According to the information processing device described in item 10, the measurement value of the target component in the target sample can be corrected using the results obtained by analyzing a standard sample that does not contain the target component.

[0110] (Item 11) A mass spectrometer according to one embodiment includes a chromatograph unit that temporally separates a target component contained in a target sample and a first reference component and a second reference component contained in a standard sample; a mass analyzer unit that measures ions having mass-to-charge ratios derived from the target component, the first reference component, and the second reference component separated by the chromatograph unit; and a controller that controls the operation of the chromatograph unit and the mass analyzer unit. The control unit acquires a feature amount of the target component and a measurement value of the target component from a chromatogram obtained by analyzing the target sample under first analytical conditions at a first timing, acquires a feature amount of the first reference component, a feature amount of the second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing the standard sample under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under second analytical conditions at a third timing, and corrects the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing. For the target component, the first reference component, and the second reference component, the measurement value of each component is a value related to the amount of the corresponding component, and the feature amount of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

[0111] According to the mass spectrometer described in item 11, the measurement value of the target component in the sample can be corrected using the results obtained by analyzing a standard sample that does not contain the target component.

[0112] (Item 12) A program according to one aspect is executed by a processor mounted on a computer. The computer acquires a feature amount of a target component and a measurement value of the target component from a chromatogram obtained by analyzing a target sample containing the target component under first analytical conditions at a first timing, acquires a feature amount of the first reference component, a feature amount of the second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing a standard sample containing a first reference component and a second reference component under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under second analytical conditions at a third timing, and corrects the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing. For the target component, the first reference component, and the second reference component, the measured value of each component is a value related to the amount of the corresponding component, and the feature amount of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

[0113] According to the program described in paragraph 12, the measurement value of the target component in the target sample can be corrected using the results obtained by analyzing a standard sample that does not contain the target component.

[0114] The embodiments disclosed herein should be considered to be illustrative in all respects and not restrictive. The scope of the present disclosure is defined by the claims, not by the description of the above embodiments, and is intended to include all modifications within the meaning and scope of the claims. Furthermore, it is intended that each technique in the embodiments can be implemented alone or, if necessary, in combination with other techniques in the embodiments to the extent possible. [Explanation of symbols]

[0115] 10 processing device, 11 processor, 12 memory, 13 input / output I / F, 20 input device, 30 display device, 40 chromatography mass spectrometer, 100 analysis system, 121 correction program.

Claims

1. A data processing method for correcting a measurement value of a target component in a target sample obtained by an analytical device equipped with a mass spectrometer or a chromatographic mass spectrometer, using a standard sample containing a first reference component and a second reference component, comprising: For the target component, the first reference component, and the second reference component, The measured value of each component is a value related to the amount of the corresponding component, The feature of each component is the retention time and / or mass-to-charge ratio of the corresponding component; The data processing method includes: acquiring a feature amount and a measurement value of the target component from a chromatogram obtained by analyzing the target sample at a first timing under first analysis conditions; acquiring a feature amount of the first reference component, a feature amount of the second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing the standard sample under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing; correcting the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing.

2. The correcting step includes: calculating an influence of the first reference component using the feature amount of the target component and the feature amount of the first reference component; calculating an influence of the second reference component using the feature amount of the target component and the feature amount of the second reference component; calculating a correction coefficient for the target component based on the measurement value of the first reference component at each timing, the measurement value of the second reference component at each timing, and the influence of the first reference component and the influence of the second reference component; 2. The data processing method according to claim 1, further comprising the step of multiplying the measured value of the target component by the correction coefficient.

3. 3. The data processing method according to claim 1, wherein the second analysis conditions are the same as the first analysis conditions.

4. 3. The data processing method according to claim 1, wherein the feature amounts of the target component, the feature amounts of the first reference component, and the feature amounts of the second reference component include at least one of a retention time, a mass-to-charge ratio, and a mass-to-charge ratio of a product ion of the corresponding component.

5. 3. The data processing method according to claim 1, wherein the measurement value of the target component, the measurement value of the first reference component, and the measurement value of the second reference component are calculated based on at least one of a peak area and a peak intensity in a chromatogram of the corresponding component.

6. 3. The data processing method according to claim 2, wherein each of the steps of calculating the influence degree of the first reference component and calculating the influence degree of the second reference component determines the corresponding influence degree using at least one of a multidimensional Gaussian distribution function and a multidimensional Cauchy distribution function.

7. 3. The data processing method according to claim 2, wherein in each of the steps of calculating the influence degree of the first reference component and calculating the influence degree of the second reference component, the corresponding influence degree increases as the difference between the feature amounts of the target component and the corresponding reference component decreases.

8. The step of calculating the influence of the first reference component and the step of calculating the influence of the second reference component each include calculating the retention time of the target component as RT Ｔ and the retention time of the corresponding reference component is RT Ｑ and the mass-to-charge ratio of the target component is mz1 Ｔ and the mass-to-charge ratio of the corresponding reference component is mz1 Ｑ and the mass-to-charge ratio of the product ion of the target component is mz2 Ｔ and the mass-to-charge ratio of the product ion of the corresponding reference component is mz2 Ｑ 3. The data processing method according to claim 2, wherein, when σRT, σmz1, σmz2, and C are predetermined numbers, the corresponding influence degree is calculated using equation (1). [Equation 1]

9. The step of calculating the influence of the first reference component and the step of calculating the influence of the second reference component each include calculating the retention time of the target component as RT Ｔ and the retention time of the corresponding reference component is RT Ｑ and the mass-to-charge ratio of the target component is mz1 Ｔ and the mass-to-charge ratio of the corresponding reference component is mz1 Ｑ and the mass-to-charge ratio of the product ion of the target component is mz2 Ｔ and the mass-to-charge ratio of the product ion of the corresponding reference component is mz2 Ｑ 3. The data processing method according to claim 2, wherein, when σRT, σmz1, σmz2, and C are predetermined numbers, the corresponding influence degree is calculated by equation (2). [Equation 2]

10. at least one processor; memory accessible to the one or more processors; the memory stores one or more instructions to be executed by the processor; The processor executes the one or more instructions to: a target sample containing a target component is analyzed under first analytical conditions at a first timing, and from the chromatogram obtained, a feature amount of the target component and a measurement value of the target component are obtained; obtaining a feature amount of the first reference component, a feature amount of the second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing a standard sample containing a first reference component and a second reference component under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing; correcting the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing; For the target component, the first reference component, and the second reference component, The measured value of each component is a value related to the amount of the corresponding component, The feature amount of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

11. a chromatograph unit that temporally separates a target component contained in a target sample and a first reference component and a second reference component contained in a standard sample; a mass spectrometric unit for measuring ions having mass-to-charge ratios derived from the target component, the first reference component, and the second reference component separated in the chromatographic unit; a control unit that controls the operations of the chromatograph unit and the mass spectrometer unit, The control unit acquiring a feature amount and a measurement value of the target component from a chromatogram obtained by analyzing the target sample under first analysis conditions at a first timing; obtaining a feature amount of the first reference component, a feature amount of the second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing the standard sample under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing; correcting the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing; For the target component, the first reference component, and the second reference component, The measured value of each component is a value related to the amount of the corresponding component, A chromatographic mass spectrometer, wherein the feature of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

12. A program executed by a processor installed in a computer, the computer a target sample containing a target component is analyzed under first analytical conditions at a first timing, and from the chromatogram obtained, a feature amount of the target component and a measurement value of the target component are obtained; obtaining a feature amount of the first reference component, a feature amount of the second reference component, a measurement value of the first reference component at each timing, and a measurement value of the second reference component at each timing from a chromatogram obtained by analyzing a standard sample containing a first reference component and a second reference component under the first analytical conditions at a second timing and a chromatogram obtained by analyzing the standard sample under the second analytical conditions at a third timing; correcting the measurement value of the target component based on the feature amount of the target component, the feature amount of the first reference component, the feature amount of the second reference component, the measurement value of the first reference component at each timing, and the measurement value of the second reference component at each timing; For the target component, the first reference component, and the second reference component, The measured value of each component is a value related to the amount of the corresponding component, The feature of each component is the retention time and / or mass-to-charge ratio of the corresponding component.

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