Chromatogram data processing method and system

Abstract

To shorten a time for separating peaks derived from a plurality of components overlapping on a chromatogram.SOLUTION: First data including chromatogram data composed of a retention time and a signal intensity of light having a predetermined wavelength obtained from chromatographic analysis and second data which is three dimensional data composed of a retention time, a mass-to-charge ratio, and a signal intensity are prepared, and information on a waveform of a target peak and a retention time range in which the target peak is present is acquired from a chromatogram created based on the first data. A model function representing a peak waveform including the number of component peaks as a variable is prepared, and initial values of the number of component peaks and the retention time are set based on the number of peaks and the retention time located within the retention time range of a three dimensional graph created based on the second data. A peak waveform expressed by the model function is applied to an object peak while changing a variable of the model function, and an object peak model function expressing a waveform of the object peak is determined.SELECTED DRAWING: Figure 1

Description

[Technical Field]

[0001] The present invention relates to a chromatogram data processing method and system. [Background technology]

[0002] In liquid chromatography (LC) using a multichannel detector such as a photodiode array (PDA) detector, three-dimensional data consisting of time, wavelength, and signal intensity (absorbance) can be obtained by continuously acquiring the absorption spectrum of the sample eluting from the analytical column.

[0003] When quantifying a target component in a sample using a liquid chromatograph, a chromatogram is typically created using the wavelength at which the target component has the greatest absorbance, and the quantification is performed by determining the area value of the peak of the target component on the chromatogram. However, there are cases where the sample contains impurities other than the target component, and the peaks of the impurities overlap with the peak of the target component to form a single peak. In such cases, in order to determine the peak area value of the target component from the peak of the target component that overlaps with the peak of the impurities, it is necessary to separate the peaks of the impurities from the peak of the target component.

[0004] A known method for separating a peak formed by overlapping peaks (component peaks) derived from multiple components into individual component peaks is to use a model function representing a peak waveform, such as an Exponential Modified Gaussian (EMG) function or a Bidirectional Exponential Modified Gaussian (BEMG) function (see Patent Document 1). In this method, a peak to be analyzed (target peak) is extracted from a chromatogram. First, a peak waveform is generated using a model function assuming that the number of component peaks contained in the target peak is one, and the generated peak waveform is fitted to the target peak. In the fitting process, initial values ​​of the model function variables are set using random numbers or the like, and the variables are changed to find a model function representing a peak waveform closest to the target peak. An index (similarity) is then calculated to evaluate the degree to which the peak waveform represented by the model function approximates the target peak. If the similarity value is outside a predetermined range, the number of component peaks is increased by one, and a peak waveform (synthetic waveform) consisting of the sum of the model functions corresponding to each component peak is fitted to the target peak. This fitting process is repeated while increasing the number of component peaks until the similarity value falls within a predetermined range, thereby estimating the number of component peaks contained in the target peak and the waveform of each component peak. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] International Publication No. 2016 / 035167 Summary of the Invention [Problem to be solved by the invention]

[0006] Because the number of component peaks contained in a target peak is typically unknown, the method disclosed in Patent Document 1 begins the above fitting process assuming the number of component peaks is one. Therefore, if the target peak actually contains multiple component peaks, it takes time to estimate the correct number of component peaks. Furthermore, in the above fitting process, a model function is prepared for each component peak estimated to be contained in the target peak, and the variables of the model function are adjusted. A model function has multiple variables. For example, the BEMG function, which can represent the tailing (the trailing portion of the peak) and leading (the leading portion of the peak) of the peak waveform in an actual chromatogram, has five variables indicating the peak position (retention time), height, width, degree of tailing, and degree of leading. When the BEMG function is used as the model function, each additional component peak to be estimated requires one more model function, resulting in five more variables to be adjusted. As the number of variables that need to be adjusted increases, the above fitting process takes time.

[0007] The problem to be solved by the present invention is to reduce the time required to separate peaks resulting from multiple components that overlap on a chromatogram. [Means for solving the problem]

[0008] The chromatogram data processing method according to the present invention, which has been made to solve the above problems, comprises: a data preparation step of preparing first data including chromatogram data consisting of retention times and signal intensities of transmitted / absorbed light at predetermined wavelengths obtained by performing chromatographic analysis on a sample containing a plurality of components, and second data which is three-dimensional data consisting of retention times, mass-to-charge ratios, and signal intensities obtained for the sample; a target peak information acquisition step of acquiring a first retention time range in which a target peak exists and a waveform shape of the target peak from a chromatogram created based on the first data; a component peak information acquisition step of acquiring, as the number of measured component peaks, the number of component peaks within a second retention time range corresponding to the first retention time range in a three-dimensional graph created based on the second data; a model function preparation step of preparing a model function including, as a variable, a peak width variable representing a peak width of the component peak, the number of which corresponds to the number of the measured component peaks; a model changing step of changing the value of each peak width variable of the model function of the number of peaks of the measured component; a similarity determination step of comparing a model peak waveform represented by a model function of the number of measured component peaks with the waveform shape of the target peak and determining the similarity between the model and the target peak; an end determination step of determining that the model change should be ended when the similarity is equal to or greater than a threshold; It has.

[0009] The chromatogram data processing system according to the present invention, which is made to solve the above problems, comprises: a data storage unit for storing first data including chromatogram data consisting of retention times and signal intensities of transmitted / absorbed light at predetermined wavelengths obtained by performing a chromatographic analysis on a sample containing a plurality of components, and second data which is three-dimensional data consisting of retention times, mass-to-charge ratios, and signal intensities obtained for the sample; a data processing unit that performs arithmetic processing using the first data and the second data stored in the data storage unit, The data processing unit a target peak information acquisition step of acquiring information about a first retention time range in which a target peak exists and a waveform shape of the target peak from a chromatogram created based on the first data stored in the data storage unit; a component peak information acquisition step of acquiring, as the number of measured component peaks, the number of component peaks within a second retention time range corresponding to the first retention time range in a three-dimensional graph created based on the second data stored in the data storage unit; a model function preparation step of preparing a model function including, as a variable, a peak width variable representing a peak width of the component peak, the number of which corresponds to the number of the measured component peaks; a model changing step of changing the value of each peak width variable of the model function of the number of peaks of the measured component; a similarity determination step of comparing a model peak waveform represented by a model function of the number of measured component peaks with the waveform shape of the target peak and determining the similarity between the model and the target peak; an end determination step of determining that the model change should be ended when the similarity is equal to or greater than a threshold; is configured to run [Effects of the Invention]

[0010] In a chromatogram data processing method and system according to the present invention, information regarding a first retention time range in which a target peak exists and the waveform shape of the target peak is obtained from a chromatogram created from chromatogram data included in first data. Next, the number of component peaks within a second retention time range corresponding to the first retention time range in a three-dimensional graph created based on second data is obtained as the number of measured component peaks. Since the number of component peaks obtained from the three-dimensional graph is considered to represent a value close to the number of component peaks actually included in the target peak, a model function including a peak width variable representing the peak width of the component peak is prepared for each of the measured component peaks. While changing the value of each peak width variable in the model function for the number of measured component peaks, the model peak waveform represented by the model function for the number of measured component peaks is compared with the waveform shape of the target peak to determine the similarity between the model and the target peak. If the similarity is equal to or greater than a threshold, the model peak waveform represented by the model function for the number of measured component peaks is determined to be similar to the waveform shape of the target peak, and the model change is terminated. This makes it possible to efficiently determine the target peak model function, and to separate peaks derived from multiple components that overlap on a chromatogram in a short time, compared to conventional techniques that determine a model function representing the target peak by assuming that the number of component peaks contained in the target peak is completely unknown. [Brief explanation of the drawings]

[0011] [Figure 1] 1 is a block diagram illustrating a schematic diagram of an embodiment of a data processing system. [Figure 2] 10 is a flowchart illustrating a series of steps related to an initial value setting process. [Figure 3] 10 is a flowchart illustrating an example of a procedure for initial value setting processing. [Figure 4] FIG. 10 is a diagram illustrating an example of a procedure for initial value setting processing. [Figure 5] 10 is a flowchart illustrating an example of a procedure for a model function estimation process. [Figure 6] FIG. 10 is a diagram showing a display example of peak separation results. DETAILED DESCRIPTION OF THE INVENTION

[0012] Hereinafter, embodiments of a chromatogram data processing method and system according to the present invention will be described with reference to the drawings.

[0013] FIG. 1 shows an embodiment of a chromatogram data processing system.

[0014] The data processing system 1 includes a data processing device 2, an input device 3, and a display 4. The data processing device 2 is realized by a computer device such as a personal computer with a dedicated program installed. The input device 3 is realized by a keyboard and / or a mouse connected to the data processing device 2 so as to be able to communicate with the data processing device 2. A user can input information to the data processing device 2 via the input device 3. The display 4 is connected to the data processing device 2 so as to be able to communicate with the data processing device 2, and displays information output from the data processing device 2.

[0015] The data processing device 2 includes an analytical data storage unit 5, a unit model function storage unit 6, and a data processing unit 7. The analytical data acquired by the first analytical device 100 and the second analytical device 200 are input into the data processing device 2. The first analytical device 100 is configured to perform liquid chromatography analysis of a sample using a PDA detector to acquire an absorption spectrum at regular intervals. That is, the analytical data input from the first analytical device 100 to the data processing device 2 is three-dimensional data consisting of retention time, wavelength, and signal intensity of transmitted / absorbed light. The second analytical device 200 is configured to perform liquid chromatography analysis of a sample using a mass spectrometer as a detector to acquire a mass spectrum at regular intervals. That is, the analytical data input from the second analytical device 200 to the data processing device 2 is three-dimensional data consisting of retention time, mass-to-charge ratio, and signal intensity. Hereinafter, the three-dimensional data input from the first analytical device 100 to the data processing device 2 will be referred to as "first data," and the three-dimensional data input from the second analytical device 200 to the data processing device 2 will be referred to as "second data."

[0016] The analytical data storage unit 5 is a storage area for storing the first data acquired from the first analytical device 100 and the second data acquired from the second analytical device 200. The first data and second data for the same sample are stored in association with each other. The analytical data storage unit 5 can be realized by a nonvolatile flash memory, a hard disk drive, or the like.

[0017] The unit model function storage unit 6 stores one or more unit model functions prepared in advance. The unit model function is a model function that represents the waveform of a target peak (component peak) on a three-dimensional graph (hereinafter also referred to as a three-dimensional chromatogram) with axes representing retention time, wavelength, and signal intensity, respectively, obtained when a sample containing a certain component is subjected to liquid chromatography analysis using a PDA detector. When the target peak, which is created based on the first data and has axes representing retention time, wavelength, and signal intensity, respectively, includes multiple component peaks derived from multiple components (i.e., when multiple components are contained in the sample), the model function that represents the waveform of the target peak is expressed as the sum (composite function) of multiple unit model functions.

[0018] The unit model function can be expressed as the product of a function (matrix) representing the waveform of a chromatogram with the retention time and the signal intensity of a given wavelength as axes, and data (matrix) representing the waveform of a spectrum with the wavelength and the signal intensity of light as axes. An example of a model function is the BEMG function, which is a combination of a Gaussian function and an exponential function designed to reproduce peak waveforms with tailing and leading, similar to actual peak waveforms that appear in a chromatogram. The unit model function has multiple variables, including the peak position (retention time) and the spectral waveform. For example, when the BEMG function is used as a function representing the chromatogram waveform, the unit model function has variables including the peak retention time, height, width, degree of tailing and leading, and spectral waveform. The unit model function storage unit 6 can be realized by a non-volatile flash memory or a hard disk drive, as with the analysis data storage unit 5, but can also be realized by a database installed on a network.

[0019] The data processing unit 7 processes the first data and the second data stored in the analysis data storage unit 5. The data processing by the data processing unit 7 includes a quantification process in which a chromatogram is created based on the first data and the concentrations of components contained in the sample are quantified from the area values ​​of the peaks on the chromatogram, and a peak separation process in which, when multiple component peaks derived from the components contained in the sample overlap each other on the chromatogram, each component peak is separated. The peak separation process is performed by the functions of a peak information acquisition unit 71, a component peak number estimation unit 72, an initial value setting unit 73, and a model function estimation unit 74 of the data processing unit 7.

[0020] The peak information acquisition unit 71 extracts a target peak to be analyzed from a three-dimensional graph created based on the first data, and acquires information about the waveform of the target peak (chromatogram waveform and spectrum waveform) and the range in which the target peak exists (retention time range and wavelength range). The component peak number estimation unit 72 extracts peaks derived from component peaks that are likely to be included in the target peak from a three-dimensional graph created based on the second data, with retention time, mass-to-charge ratio, and signal intensity as axes, and reads the retention time of each extracted peak.

[0021] The initial value setting unit 73 sets initial values ​​for the number of component peaks (the number of unit model functions) and the retention time of each component peak (the retention time of each unit model function), which are variables of the model function representing the target peak, based on the number of peaks extracted by the component peak number estimation unit 72 and the retention time of each peak. The model function estimation unit 74 reads unit model functions from the unit model function storage unit 6 in quantities equal to the number of component peaks, based on information about the waveform of the target peak acquired by the peak information acquisition unit 71 and the initial values ​​set by the initial value setting unit 73, and creates a composite model function consisting of the sum of these unit model functions. Note that if the number of component peaks is one, the composite model function is the unit model function itself. Furthermore, in this embodiment, if the number of component peaks is two or more, two or more identical unit model functions are read from the unit model function storage unit 6 to create the composite model function, but different unit model functions may also be read to create the composite model function. Here, the retention time of each component peak refers to the peak width of each component peak.

[0022] When the model function estimation unit 74 creates the composite model function, it executes a process of fitting the peak waveform represented by the composite model function to the target peak while adjusting each variable of the composite model function, thereby obtaining a model function representing the waveform of the target peak. Each function of the data processing unit 7 is realized by executing a program in a computer circuit equipped with a CPU (Central Processing Unit).

[0023] The following describes a series of steps related to the initial value setting process using the flowchart in FIG.

[0024] First, when the user specifies first data to be analyzed, the data processing unit 7 reads the specified first data (step S101). The data processing unit 7 creates a first three-dimensional graph from the read first data (step S102), displays the three-dimensional graph on the display 4 communicably connected to the data processing system 1, and prompts the user to specify a retention time range and a wavelength range to be analyzed (step S103). Thereafter, when the user inputs an instruction to execute an initial value setting process, the data processing unit 7 executes the initial value setting process (step S104).

[0025] The procedure for the initial value setting process will be described with reference to the flowchart of FIG. 3 and FIG.

[0026] When the initial value setting process starts, the peak information acquisition unit 71 extracts a portion within the retention time range of the specified analysis target from the first three-dimensional graph created in step S102 as a target peak, and acquires the waveform of the target peak (chromatogram waveform and spectrum waveform) and information about the first retention time range in which the target peak exists (step S201). At this point, it is not known whether the target peak consists of a single component peak or multiple component peaks.

[0027] Next, the component peak number estimation unit 72 reads the second data (step S202), and creates a second three-dimensional graph including a mass chromatogram showing the time change of the signal intensity at each mass-to-charge ratio and a mass spectrum showing the relationship between the signal intensity and the mass-to-charge ratio from the second data (step S203). Then, in the second retention time range corresponding to the first retention time range acquired in step S201, the first retention time (for example, RT A) and count the number of peaks having an intensity equal to or greater than a predetermined intensity value. Here, the first retention time range and the second retention time range may be the same time range, or there may be a difference between the first retention time range and the second retention time range, taking into account the piping capacity and flow rate of the apparatus. If the counted number exceeds a predetermined number (for example, 5), it is determined that a component peak exists at the first retention time, and the first retention time is stored. A second retention time (for example, RT in Figure 4) different from the first retention time in the second three-dimensional graph is stored. B ) and similarly determine whether a component peak is present at all other retention times. Similarly, each retention time determined to have a component peak is stored in association with the respective component peak. The number of retention times determined to have a component peak within the retention time range is regarded as the number of measured component peaks, and the number of measured component peaks and the retention times determined to have each component peak are stored. If the spectrum at a retention time determined to have a component peak is the same spectrum as a spectrum at another retention time that has already been determined to have a component peak, there is a possibility that the same component peak has been measured in duplicate, and therefore it does not need to be included in the number of counted component peaks.

[0028] Next, the initial value setting unit 73 sets the number of measured component peaks counted in step S205 to the number of component peaks, which is a variable of a model function representing the waveform of the target peak, and sets the retention time of each component peak to the initial value of the model function of the retention time of each corresponding component peak (step S206).

[0029] For example, if the mass chromatogram for each mass-to-charge ratio in the retention time range of the analysis target is as shown in Figure 4, the retention time RT A The three peaks detected at RT were designated as component peak A, which is derived from component A contained in the sample. B If the three peaks detected in the RT A and RT ABased on this, the initial value of the number of component peaks in the model function representing the waveform of the target peak is set to 2, and the initial values ​​of the retention times of the component peaks derived from component A and component B are set to RT A , R.T. B Set to.

[0030] After the initial value setting process is completed, the model function estimation process is executed. The steps of the model function estimation process will be described with reference to the flowchart in FIG.

[0031] The model function estimation unit 74 creates unit model functions from the unit model function storage unit 6 for the number of component peaks, based on the information about the waveform of the target peak acquired in step S201 and the initial value of the number of component peaks set in step S206 (step S301). Then, the model function estimation unit 74 substitutes the initial value of the retention time of the component peak set in step S206 into a corresponding unit model function from among the created unit model functions, sets random numbers as initial values ​​for the other variables, and creates a composite model function consisting of the sum of the unit model functions (step S302). Thereafter, the model function estimation unit 74 applies the peak waveform represented by the composite model function to the target peak while adjusting each variable of the composite model function (step S303).

[0032] The fitting process in step S303 can use a known method. For example, the method disclosed in Patent Document 1 can be mentioned. In the method disclosed in Patent Document 1, a model function representing the waveform of the target peak is calculated using the least squares method. Specifically, a similarity is calculated to evaluate the degree to which the shape of the waveform of the peak represented by the model function resembles the shape of the actual waveform of the target peak, and it is determined whether the similarity exceeds a threshold (step S304). If the similarity does not exceed the threshold (No in step S304), the process returns to step S303, where the variables of the composite model function are changed and the peak waveform represented by the composite model function is fitted to the target peak again.

[0033] The composite model function variables for each peak model include a height variable representing the peak height, a width variable representing the peak width, a retention time variable representing the peak retention time, and a spectral shape variable representing the shape of the spectrum direction. When multiple model functions are used, the similarity is calculated by adding all model functions together and comparing them with the waveform of the target peak. If the maximized similarity value is equal to or less than a threshold, it is determined that the number of component peaks is insufficient. A composite model function is then created by adding one unit model function, with all variables initialized to random numbers, to the model functions after the variable adjustment. The peak waveform represented by the composite model function is then fitted to the target peak. This fitting of the peak waveform represented by the composite model function to the target peak is repeated until the similarity value exceeds a predetermined threshold. In other words, if the similarity value exceeds a predetermined threshold (Yes in step S304), it is determined that the peak waveform represented by the composite model function and the waveform of the target peak are similar, and the fitting process is terminated.

[0034] Through the above processing, the number of component peaks contained in the target peak and the waveforms of each component peak (chromatogram waveform and spectrum waveform) are estimated, and multiple component peaks that overlap on the chromatogram can be separated from each other. The results of peak separation are shown on display 4. Figure 6 shows an example of the peak separation results.

[0035] (Variation) In the above embodiment, the number of component peaks counted in step S205 is set as the initial value for the number of component peaks. However, a value that is a predetermined number smaller than the number of component peaks counted in step S205 may be set as the initial value for the number of component peaks. While the number of component peaks counted in step S205 is likely to be the number of component peaks actually contained in the target peak, it is possible that a number of component peaks greater than the number of component peaks actually contained in the target peak may be detected. In this case, the model function estimation process from step S301 onward is started with the initial value for the number of component peaks of the model function set to a value greater than the actual number of component peaks. In the model function estimation process, the number of component peaks is increased from the initial value to approximate the composite model function to the actual target peak. Therefore, if the initial value for the number of component peaks is set to a value greater than the actual number, the correct number of component peaks cannot be estimated. For example, if a value (but not less than 1) that is one less than the number of component peaks counted in step S205 is set as the initial value for the number of component peaks in the model function, it is possible to avoid a situation in which the correct number of component peaks cannot be estimated even if one more component peak than the number of component peaks actually contained in the target peak is counted in step S205. Furthermore, in the process of counting component peaks in step S205, in order to extract peaks derived from component peaks that are highly likely to be contained in the target peak, only component peaks from which a predetermined number or more peaks have been extracted may be counted in multiple mass chromatograms with different mass-to-charge ratios, and the counted value may be set as the initial value for the number of component peaks in the model function.

[0036] In the above embodiment, a three-dimensional graph is created based on the first data, and both a chromatogram waveform and a spectral waveform are estimated for the component peaks included in the target peak on the three-dimensional graph. However, a chromatogram (two-dimensional chromatogram) may be created based on chromatogram data consisting of retention time and signal intensity of light of a predetermined wavelength from the first data, and a chromatogram waveform may be estimated for the component peaks included in the target peak on the chromatogram. In this case, the unit model function is expressed by a function that represents the peak waveform of the chromatogram.

[0037] [Aspect] It will be apparent to those skilled in the art that the above-described exemplary embodiments are examples of the following aspects.

[0038] (Item 1) A chromatogram data processing method according to one aspect of the present invention includes: a data preparation step of preparing first data including chromatogram data consisting of retention times and signal intensities of transmitted / absorbed light at predetermined wavelengths obtained by performing chromatographic analysis on a sample containing a plurality of components, and second data which is three-dimensional data consisting of retention times, mass-to-charge ratios, and signal intensities obtained for the sample; a target peak information acquisition step of acquiring a first retention time range in which a target peak exists and a waveform shape of the target peak from a chromatogram created based on the first data; a component peak information acquisition step of acquiring, as the number of measured component peaks, the number of component peaks within a second retention time range corresponding to the first retention time range in a three-dimensional graph created based on the second data; a model function preparation step of preparing a model function including, as a variable, a peak width variable representing a peak width of the component peak, the number of which corresponds to the number of the measured component peaks; a model changing step of changing the value of each peak width variable of the model function of the number of peaks of the measured component; a similarity determination step of comparing a model peak waveform represented by a model function of the number of measured component peaks with the waveform shape of the target peak and determining the similarity between the model and the target peak; an end determination step of determining that the model change should be ended when the similarity is equal to or greater than a threshold; It has.

[0039] (Item 6) A chromatogram data processing system according to one aspect of the present invention comprises: a data storage unit for storing first data including chromatogram data consisting of retention times and signal intensities of transmitted / absorbed light at predetermined wavelengths obtained by performing a chromatographic analysis on a sample containing a plurality of components, and second data which is three-dimensional data consisting of retention times, mass-to-charge ratios, and signal intensities obtained for the sample; a data processing unit that performs arithmetic processing using the first data and the second data stored in the data storage unit, The data processing unit a target peak information acquisition step of acquiring information about a first retention time range in which a target peak exists and a waveform shape of the target peak from a chromatogram created based on the first data stored in the data storage unit; a component peak information acquisition step of acquiring, as the number of measured component peaks, the number of component peaks within a second retention time range corresponding to the first retention time range in a three-dimensional graph created based on the second data stored in the data storage unit; a model function preparation step of preparing a model function including, as a variable, a peak width variable representing a peak width of the component peak, the number of which corresponds to the number of the measured component peaks; a model changing step of changing the value of each peak width variable of the model function of the number of peaks of the measured component; a similarity determination step of comparing a model peak waveform represented by a model function of the number of measured component peaks with the waveform shape of the target peak and determining the similarity between the model and the target peak; an end determination step of determining that the model change should be ended when the similarity is equal to or greater than a threshold; is configured to run

[0040] According to the chromatogram data processing method of paragraph 1 and the chromatogram data processing system of paragraph 6, the target peak model function can be determined more efficiently than in the prior art, which determines a model function representing a target peak on the assumption that the number and retention times of component peaks contained in the target peak are completely unknown, and peaks resulting from multiple components that overlap on a chromatogram can be separated in a short time.

[0041] Furthermore, in peak waveform fitting processing, as the number of variables in the model function increases, the degree of statistical freedom increases, making it difficult to estimate the variables and resulting in unstable data processing operations. According to the chromatogram data processing method of paragraph 1 and the chromatogram data processing system of paragraph 4, peak waveform fitting processing is performed from a state in which initial values ​​with a certain degree of accuracy are given, thereby improving the accuracy of estimation of the number of component peaks, the shapes and magnitudes of the component peaks, etc. Furthermore, since the time required to estimate the number of models can be reduced, the time required for estimation can be shortened.

[0042] (Item 2) In the chromatogram data processing method according to item 1, The model function further includes a retention time variable representing the retention time of a component peak as a variable; In the component peak information acquisition step, a measured component retention time representing the retention time of each component peak is acquired; The method may include an initial value setting step of setting the retention time of the measured component as the retention time variable.

[0043] (7) In the chromatogram data processing system according to the 6th paragraph, The model function further includes a retention time variable representing the retention time of a component peak as a variable; In the component peak information acquisition step, a measured component retention time representing the retention time of each component peak is acquired; The data processing unit further An initial value setting step of setting the retention time variable to the retention time of the measured component may be executed.

[0044] According to the chromatogram data processing method of item 2 and the chromatogram data processing system of item 7, the number of component peaks contained in a target peak and approximate values ​​of the retention time of each component peak are determined, and these are used as initial values ​​of variables of a model function representing the target peak. Therefore, the target peak model function can be determined more efficiently than in the prior art, in which the model function representing the target peak is determined on the assumption that the number of component peaks and the retention time of each component peak are completely unknown.

[0045] (Item 3) In the chromatogram data processing method according to item 1 or 2, In the component peak information acquisition step, if there are a predetermined number or more peaks exceeding a predetermined threshold at a predetermined retention time within the retention time range in the second three-dimensional graph created based on the second data, it can be determined that there is one component peak at the predetermined retention time.

[0046] (Item 8) In the chromatogram data processing system according to item 6 or 7, In the component peak information acquisition step, if there are a predetermined number or more peaks exceeding a predetermined threshold at a predetermined retention time within the retention time range in the second three-dimensional graph created based on the second data, it can be determined that there is one component peak at the predetermined retention time.

[0047] If the number of component peaks contained in a target peak is estimated to be larger than the actual number, it may be impossible to correctly determine a model function representing the target peak, or the process of estimating the model function may take a long time. The chromatogram data processing method according to paragraph 3 and the chromatogram data processing system according to paragraph 8 can prevent an incorrect model function from being estimated.

[0048] (Item 4) In the chromatogram data processing method according to any one of items 1 to 3, the first data includes spectral data consisting of signal intensity and wavelength of transmitted / absorbed light; the target peak is a three-dimensional peak extracted from a three-dimensional chromatogram created from the first data, The model function may include, as variables, the number of component peaks, the retention time of each component peak, and the waveform of a spectrum created from the spectrum data.

[0049] (Item 9) In the chromatogram data processing system according to any one of items 6 to 8, the first data includes spectral data consisting of signal intensity and wavelength of transmitted / absorbed light; the target peak is a three-dimensional peak extracted from a three-dimensional chromatogram created from the first data, The model function may include, as variables, the number of component peaks, the retention time of each component peak, and the waveform of a spectrum created from the spectrum data.

[0050] In the chromatogram data processing method according to paragraph 4 and the chromatogram processing system according to paragraph 9, the first data is three-dimensional data including chromatogram data consisting of retention time and signal intensity of transmitted / absorbed light, and spectrum data consisting of signal intensity and wavelength of transmitted / absorbed light. A three-dimensional chromatogram refers to a three-dimensional graph created based on the three-dimensional data. According to the chromatogram data processing method according to the fourth aspect and the chromatogram processing system according to the seventh aspect, component peaks derived from a plurality of components can be separated not only on a chromatogram but also on a spectrum.

[0051] (Item 5) In the chromatogram data processing method according to any one of items 1 to 4, the model function may include a function that combines a Gaussian function and an exponential function.

[0052] (Item 10) In the chromatogram data processing system according to any one of items 6 to 9, the model function may include a function that combines a Gaussian function and an exponential function.

[0053] In the chromatogram data processing method according to item 5 and the chromatogram data processing system according to item 10, the peak waveform of an actual chromatogram can be reproduced with high accuracy using the model function, thereby improving the accuracy of component peak estimation. [Explanation of symbols]

[0054] 1...Data processing system 2...Data processing device 3...Input device 4. Display 5...Analysis data storage section 6...Unit model function memory section 7...Data processing unit 71...Peak information acquisition unit 72...Component peak number estimation section 73...Initial value setting section 74...Model function estimation section 100...1st analysis device 200…Second analysis device

Claims

1. a data preparation step of preparing first data including chromatogram data consisting of retention times and signal intensities of transmitted / absorbed light at predetermined wavelengths obtained by performing chromatographic analysis on a sample containing a plurality of components, and second data which is three-dimensional data consisting of retention times, mass-to-charge ratios, and signal intensities obtained for the sample; a target peak information acquisition step of acquiring a first retention time range in which a target peak exists and a waveform shape of the target peak from a chromatogram created based on the first data; a component peak information acquisition step of acquiring, as a measured component peak number, the number of component peaks within a second retention time range corresponding to the first retention time range in a three-dimensional graph created based on the second data; a model function preparation step of preparing a model function including, as a variable, a peak width variable representing a peak width of the component peak, the number of which corresponds to the number of the measured component peaks; a model changing step of changing the value of each peak width variable of the model function of the number of peaks of the measured component; a similarity determination step of comparing a model peak waveform represented by a model function of the number of measured component peaks with the waveform shape of the target peak and determining the similarity between the model and the target peak; an end determination step of determining that the model change should be ended when the similarity is equal to or greater than a threshold; A chromatogram data processing method comprising:

2. The model function further includes a retention time variable representing the retention time of a component peak as a variable; In the component peak information acquisition step, a measured component retention time representing the retention time of each component peak is acquired; 2. The chromatogram data processing method according to claim 1, further comprising an initial value setting step of setting the retention time of the measured component to the retention time variable.

3. 2. The chromatogram data processing method according to claim 1, wherein in the component peak information acquisition step, when there are a predetermined number or more peaks exceeding a predetermined threshold at a predetermined retention time within the retention time range in a second three-dimensional graph created based on the second data, it is determined that there is one component peak at the predetermined retention time.

4. the first data includes spectral data consisting of signal intensities and wavelengths of transmitted / absorbed light; the target peak is a three-dimensional peak extracted from a three-dimensional chromatogram created from the first data, the model function further includes a spectral waveform variable relating to the waveform of the spectrum; The chromatogram data processing method according to claim 1 , wherein the waveform of the spectrum is adjusted in the target peak model function estimation step.

5. 5. The chromatogram data processing method according to claim 1, wherein the model function includes a function that combines a Gaussian function and an exponential function.

6. a data storage unit for storing first data including chromatogram data obtained by performing a chromatographic analysis on a sample containing a plurality of components, the chromatogram data being composed of retention times and signal intensities of transmitted / absorbed light at predetermined wavelengths, and second data being three-dimensional data obtained for the sample and being composed of retention times, mass-to-charge ratios, and signal intensities; a data processing unit that performs arithmetic processing using the first data and the second data stored in the data storage unit, The data processing unit a target peak information acquisition step of acquiring information about a first retention time range in which a target peak exists and a waveform shape of the target peak from a chromatogram created based on the first data stored in the data storage unit; a component peak information acquisition step of acquiring, as a measured component peak number, the number of component peaks within a second retention time range corresponding to the first retention time range in a three-dimensional graph created based on the second data stored in the data storage unit; a model function preparation step of preparing a model function including, as a variable, a peak width variable representing a peak width of the component peak, the number of which corresponds to the number of the measured component peaks; a model changing step of changing the value of each peak width variable of the model function of the number of peaks of the measured component; a similarity determination step of comparing a model peak waveform represented by a model function of the number of measured component peaks with the waveform shape of the target peak and determining the similarity between the model and the target peak; an end determination step of determining that the model change should be ended when the similarity is equal to or greater than a threshold; 1. A chromatogram data processing system configured to:

7. The model function further includes a retention time variable representing the retention time of a component peak as a variable; In the component peak information acquisition step, a measured component retention time representing the retention time of each component peak is acquired; The data processing unit further 7. The chromatogram data processing method according to claim 6, further comprising the step of setting an initial value for the retention time variable to the retention time of the measured component.

8. 7. The chromatogram data processing method according to claim 6, wherein in the component peak information acquisition step, when there are a predetermined number or more peaks exceeding a predetermined threshold at a predetermined retention time within the retention time range in a second three-dimensional graph created based on the second data, it is determined that there is one component peak at the predetermined retention time.

9. the first data includes spectral data consisting of signal intensities and wavelengths of transmitted / absorbed light; the target peak is a three-dimensional peak extracted from a three-dimensional chromatogram created from the first data, the model function further includes a spectral waveform variable relating to the waveform of the spectrum; The chromatogram data processing system according to claim 6 , wherein the waveform of the spectrum is adjusted in the target peak model function estimation step.

10. 10. The chromatogram data processing system according to claim 6, wherein the model function includes a function that combines a Gaussian function and an exponential function.

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