Compound determination method and compound determination system by mass spectrometry

Abstract

To make it possible to easily determine, after determining whether or not a given compound is contained in a sample by mass spectrometry, whether or not another compound which newly required determination is contained in the sample.SOLUTION: Mass analysis data is obtained by scanning with a mass spectrometer for the sample (11), whether or not a predetermined compound is contained in the sample is determined based on the data (14), a data set associating the mass analysis data and information identifying the compound that has been determined with an ID of the sample is created (16), a database is constructed by accumulating the data sets created for a plurality of samples, a data set for a sample to be re-determined out of the plurality of samples is read from the database, to determine whether or not the compound to be re-determined, including a compound other than the determined compound, has been contained in the sample to be re-determined, based on the mass spectrometry data contained in the data set.SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to a compound determination method and a compound determination system by mass spectrometry. [Background technology]

[0002] 2. Description of the Related Art In recent years, simultaneous multi-component analysis using a mass spectrometer is commonly carried out in various fields, such as testing for pesticide residues in food, testing for pollutants in environmental water, and testing for drugs and poisons.

[0003] In such multi-component simultaneous analysis, information regarding a large number of compounds that may be contained in a sample is registered in advance in a database (compound library), and based on the data obtained by mass spectrometry of the sample, a determination is made as to whether or not each of the compounds registered in the compound library (or compounds specified by the user from among them) is contained in the sample.

[0004] In such a multi-component simultaneous analysis, multiple reaction monitoring (MRM) measurements are often performed using a tandem mass analyzer such as a triple quadrupole mass analyzer (see, for example, Patent Document 1). The tandem mass analyzer includes an ion source for ionizing a sample, a front-stage mass separation section for selecting ions generated in the ion source based on m / z (mass-to-charge ratio), a collision cell for fragmenting ions (precursor ions) that have passed through the front-stage mass separation section, a rear-stage mass separation section for selecting product ions generated in the collision cell based on m / z, and a detector for detecting ions that have passed through the rear-stage mass separation section. In the MRM measurement, the m / z of the ions that pass through the front-stage mass separation section and the rear-stage mass separation section are fixed, and the intensity of a specific product ion generated from a specific precursor ion is measured. In MRM measurements, ions derived from components not being measured or impurities, as well as unionized neutral particles, are removed using two mass separation sections, one at the front and one at the rear. This makes it possible to obtain ion intensity signals with a high S / N ratio even in the simultaneous analysis of samples containing multiple target components or in the analysis of samples containing many impurities. [Prior art documents] [Patent documents]

[0005] [Patent Document 1] JP 2018-136266 A [Patent Document 2] International Publication No. 2018 / 008149 (

[0003] -

[0004] ) Summary of the Invention [Problem to be solved by the invention]

[0006] In the above-mentioned multi-component simultaneous analysis, after a sample is analyzed by MRM measurement, it may be discovered that a compound that was not expected at the time of the sample analysis was mixed into the sample, or it may be necessary to determine whether or not a newly regulated compound was contained in the sample. However, in MRM measurement, a combination of m / z of ions passing through the front-stage mass separation unit and m / z of ions passing through the rear-stage mass separation unit (called an MRM transition) is set in advance for each compound to be determined, and an ion intensity signal is acquired for each MRM transition, so that after the sample analysis is completed, it is not possible to determine whether or not a compound that was not expected in advance was contained in the sample.

[0007] The present invention has been made in consideration of the above-mentioned points, and an object of the present invention is to make it possible, after a determination of whether or not a specific compound is contained in a sample has been made by mass spectrometry, to easily determine whether or not a new compound that needs to be determined is contained in the sample. [Means for solving the problem]

[0008] The compound determination method by mass spectrometry according to the present invention, which has been achieved to solve the above problems, comprises: a mass spectrometry step of acquiring mass spectrometry data by performing a scan measurement on the sample to be determined using a mass spectrometer; a determination step of determining whether or not each of one or more compounds is contained in the target sample based on the mass spectrometry data; a data set creation step of creating a data set in which the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, are associated with information identifying the determination target sample; a database construction step of performing the mass spectrometry step, the determination step, and the data set creation step for each of a plurality of samples as the determination target sample, and constructing a database by accumulating the data sets created for each of the plurality of samples; a re-evaluation step of reading out from the database the data set relating to a sample to be re-evaluated among the plurality of samples, and determining, based on the mass spectrometry data included in the data set, whether or not each of the re-evaluation target compounds, which is one or more compounds including a compound other than the determined compound identified from the data set, is included in the sample to be re-evaluated; It has the following characteristics.

[0009] The compound determination system by mass spectrometry according to the present invention, which has been developed to solve the above problems, comprises: a determination unit that determines whether or not each of one or more compounds is contained in a target sample based on mass spectrometry data obtained by performing a scan measurement on the target sample using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, in a database in association with information identifying the determination target sample; a re-evaluation target sample designation receiving unit for receiving, from a user, designation of a sample to be re-evaluated from among a plurality of evaluation target samples registered in the database; a re-evaluation target compound designation receiving unit that receives, from a user, designation of a re-evaluation target compound, which is one or more compounds to be re-evaluated; an undetermined compound identification unit that reads out from the database information identifying the determined compounds stored for the sample to be re-evaluated, and identifies undetermined compounds that are not included in the determined compounds among the compounds to be re-evaluated; a re-evaluation unit that reads out the mass spectrometry data stored for the sample to be re-evaluated from the database and determines whether or not each of the undetermined compounds was contained in the sample to be re-evaluated based on the mass spectrometry data; It has the following characteristics.

[0010] The compound determination system by mass spectrometry according to the present invention, which has been developed to solve the above problems, comprises: a determination unit that determines whether or not each of one or more compounds is contained in a target sample based on mass spectrometry data obtained by performing a scan measurement on the target sample using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, in a database in association with information identifying the determination target sample; a re-evaluation target sample designation receiving unit for receiving, from a user, designation of a sample to be re-evaluated from among a plurality of evaluation target samples registered in the database; a re-evaluation target compound designation receiving unit that receives, from a user, designation of a re-evaluation target compound, which is one or more compounds to be re-evaluated; a re-evaluation unit that reads out the mass spectrometry data stored for the sample to be re-evaluated from the database, and determines whether or not each of the compounds to be re-evaluated is contained in the sample to be re-evaluated based on the mass spectrometry data; having The re-evaluation target compound designation receiving unit may read out information identifying the determined compound stored for the sample to be re-evaluated from the database, and may prevent the user from designating the determined compound as the compound to be re-evaluated.

[0011] The compound determination system by mass spectrometry according to the present invention, which has been developed to solve the above problems, comprises: a determination unit that determines whether or not each of one or more compounds is contained in a target sample based on mass spectrometry data obtained by performing a scan measurement on the target sample using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, in a database in association with information identifying the determination target sample; a re-evaluation target sample designation receiving unit for receiving, from a user, designation of a sample to be re-evaluated from among the plurality of evaluation target samples registered in the database; a determined compound presenting unit that reads out information for identifying the determined compound stored in the sample to be re-evaluated from the database and presents the information to a user; a re-evaluation target compound designation receiving unit for receiving designation of re-evaluation target compounds, which are one or more compounds to be re-evaluated, from a user; a re-evaluation unit that reads out the mass spectrometry data stored for the sample to be re-evaluated from the database, and determines whether or not each of the compounds to be re-evaluated is contained in the sample to be re-evaluated based on the mass spectrometry data; The present invention may also have the following structure. Effect of the Invention

[0012] According to the compound determination method or compound determination system by mass spectrometry of the present invention, once a determination is made by mass spectrometry as to whether or not a specific compound is contained in a sample, it becomes possible to easily determine whether or not a new compound that needs to be determined is contained in the sample. [Brief description of the drawings]

[0013] [Figure 1] FIG. 1 is a block diagram showing a configuration of a main part of a compound determination system according to one embodiment of the present invention. [Diagram 2] 4 is a flowchart showing a procedure for determining a sample using the compound determination system. [Diagram 3] 4 is a flowchart showing a procedure for re-evaluating a sample using the compound determination system. [Figure 4] FIG. 2 is a diagram showing the first half of a list of compounds to be determined in one embodiment of the present invention. [Diagram 5] FIG. 13 is a diagram showing the latter half of the list of compounds to be determined. [Figure 6] 2 is an extracted ion chromatogram relating to the target compound. [Figure 7] FIG. 2 shows compounds to be re-evaluated in the above examples. [Figure 8] 4 is an extracted ion chromatogram relating to the compound to be re-evaluated. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0014] Hereinafter, an embodiment of the present invention will be described with reference to the drawings. Fig. 1 is a block diagram showing the main components of a compound determination system (hereinafter, simply referred to as the system) according to this embodiment. This system includes an analysis section 100 that performs sample analysis, and a control / processing section 200 that controls the operation of the analysis section 100 and processes data obtained by the analysis.

[0015] The analysis section 100 includes an LC section 110 that fractionates a sample by high performance liquid chromatography (HPLC) and an MS section 120 that is made up of a mass analyzer. The MS section 120 includes an ionization section 121 that ionizes components in a sample, a mass separation section 122 that separates the ionized sample components according to m / z, and a detector 123 that detects separated ions. The mass analyzer constituting the MS section 120 may be any type that can perform a scan measurement, but it is preferable to use a high-resolution mass analyzer with a mass resolution M / dM of 10,000 or more (where M is the m / z of a peak on the mass spectrum, and dM is the half-width of the peak). As such a mass analyzer, for example, a time-of-flight mass analyzer (TOF-MS) or a quadrupole time-of-flight mass analyzer (QTOF-MS) can be suitably used, and an Orbitrap mass analyzer or a Fourier transform mass analyzer (FTMS) can also be used.

[0016] The control / processing unit 200 is composed of a general-purpose computer such as a personal computer or a dedicated computer, or a combination thereof, and includes, as functional blocks, an analysis control unit 201, an analysis data processing unit 202, a display control unit 203, a judgment unit 204, a database registration unit 205, an undetermined compound specification unit 206, and a re-determination unit 207. Note that all of these functional blocks are basically functional means realized in the form of software by a CPU provided in a computer constituting the control / processing unit 200 reading out a dedicated program installed in a storage unit consisting of a large-capacity storage device such as a HDD (Hard Disk Drive) or SSD (Solid State Drive) into the memory of the computer and executing it. A display unit 221 consisting of a liquid crystal display device or the like, and an operation unit 222 consisting of a pointing device such as a keyboard or a mouse are connected to the control / processing unit 200.

[0017] Furthermore, the control / processing unit 200 includes a compound library 211 and a determination result database 212 (corresponding to the database in the present invention). The compound library 211 and the determination result database 212 may be provided in a storage device built into the computer constituting the control / processing unit 200, or may be provided in a storage device connected directly to the computer or via a network such as a LAN. Alternatively, they may be provided in a storage device present on another computer system accessible from the computer via the Internet, that is, in cloud computing.

[0018] In the compound library 211, for each of a plurality of compounds, at least a retention time and a peak list including peak information (m / z and intensity information) for one or more peaks observed in the mass spectrum of the compound are stored in advance in association with information identifying the compound (such as the compound name or structural formula). The mass spectrum may be either an actual measurement or a theoretical calculation based on structural information of the compound.

[0019] The system of this embodiment and the compound determination method using the same can be suitably used for multi-component simultaneous analysis in fields such as testing for pesticide residues in food, testing for pollutants in the environment, or screening for drugs, toxins or metabolites in blood or urine (e.g., doping tests).

[0020] Below, we will explain the procedure for using this system to determine whether a target sample (hereinafter referred to as a target sample) contains a specific compound (hereinafter referred to as a target compound) with reference to the flowchart in Figure 2.

[0021] First, a sample to be determined is introduced into the analysis section 100, and separation of sample components by the LC section 110 and mass analysis by the MS section 120 are performed (step 11). The operations of the LC section 110 and the MS section 120 at this time are controlled by the analysis control section 201. Various components in the sample to be determined introduced into the LC section 110 are separated by a column (not shown) provided in the LC section 110, and are eluted from the outlet of the column with a time lag. Various components eluted sequentially from the column are introduced into the MS section 120, ionized by the ionization section 121, and introduced into the mass separation section 122. In the mass separation section 122, the m / z of the ions passing through the mass separation section 122 is repeatedly scanned in a predetermined m / z range, and the ions that have passed through the mass separation section 122 are detected by the detector 123. That is, in the MS section 120, scan measurements over a predetermined m / z range are repeatedly performed on various components in the sample to be determined that are introduced sequentially over time. The detection signal from the detector 123 at this time is input to the analysis data processing unit 202 of the control / processing unit 200 via an A / D converter (not shown). The scan measurement is a normal scan measurement that does not involve ion dissociation. The m / z range in which the scan measurement is performed is not particularly limited, but can be, for example, a range of m / z 50 to 1500 (preferably m / z 100 to 1000).

[0022] The analysis data processing unit 202 creates a mass spectrum for each scan measurement based on data (mass spectrometry data) obtained by the analysis of the sample to be determined by the analysis unit 100, and further creates a peak list based on the mass spectrum (step 12). That is, in the analysis data processing unit 202, a mass spectrum having dimensions of m / z and ion intensity is created based on data acquired in association with the scan measurement in the mass separation unit 122. Then, one or more peaks contained in the mass spectrum are detected, and a peak list is created in which the m / z and ion intensity of each peak are listed. Note that this step may be performed after the analysis of the sample to be determined by the analysis unit 100 (step 11) is completed, or may be performed in parallel with the analysis.

[0023] Next, when the user performs a predetermined operation on the operation unit 222, a screen for specifying a target compound to be determined (target compound specification screen) is displayed on the display unit 221 under the control of the display control unit 203. On the target compound specification screen, one or more compounds can be selected from a plurality of compounds registered in the compound library 211, and when the user selects one or more compounds via the operation unit 222, the compounds are specified as target compounds to be determined (step 13). Note that, in this embodiment, the target compound to be determined is specified (step 13) after the analysis unit 100 analyzes the target sample (step 11) and the analysis data processing unit 202 creates a peak list (step 12). However, the target compound to be determined may be specified before the analysis of the target compound and the creation of the peak list.

[0024] Next, the determination unit 204 determines whether each of the target compounds is contained in the target sample (step 14). Specifically, for any of the one or more target compounds specified in step 13, the retention time and peak list of the target compound are read from the compound library 211, and the peak list is compared with a peak list obtained near the retention time from the peak list of the target sample created in step 12 to obtain the similarity between the two. Then, if the similarity is equal to or greater than a predetermined threshold, it is determined that the target compound is contained in the target sample.

[0025] When the above-mentioned judgment is completed for all of the target compounds specified in step 13, a screen showing the judgment result (i.e., whether or not each of the target compounds is contained in the target sample) is displayed on the display unit 221 under the control of the display control unit 203 (step 15).

[0026] Furthermore, the database registration unit 205 creates a data set in which all the peak lists generated in step 12 for the sample to be determined, the compounds determined to be contained in the sample to be determined (i.e., information specifying the compounds to be determined specified in step 13 (e.g., compound names), and the determination results in step 14 are associated with information for identifying the sample to be determined (e.g., sample name or number), and registers the data set in the determination result database 212 (step 16). Note that the information for identifying the sample to be determined (hereinafter referred to as sample ID) may be input by the user in this step, but may also be input by the user at any time before this step, for example, before the analysis unit 100 analyzes the sample to be determined (step 11) or when the compound to be determined is specified (step 13).

[0027] The processes of steps 11 to 16 are carried out on various samples as the samples to be determined, and the obtained data set is stored in determination result database 212, thereby constructing a database of samples that have been determined in the past.

[0028] Next, the procedure for using this system to determine whether a sample that has previously been determined to contain a specific compound (hereinafter referred to as a determined sample) contains a compound other than the specific compound (this is called re-determination) will be explained with reference to the flowchart in Figure 3.

[0029] First, the user performs a predetermined operation on the operation unit 222, and a re-evaluation target sample designation screen is displayed on the display unit 221 under the control of the display control unit 203. The re-evaluation target sample designation screen is configured to be able to accept, for example, an input of a sample ID from the user, and the user operates the operation unit 222 to designate a sample to be re-evaluated on the screen (hereinafter referred to as a re-evaluation target sample) (step 21). That is, in this step, the display control unit 203, the display unit 221, and the operation unit 222 function as a re-evaluation target sample designation receiving unit in the present invention. When the user inputs a desired sample ID on the re-evaluation target sample designation screen, the determination result database 212 is searched using the sample ID as a query, and a list of multiple peaks related to the determined sample corresponding to the sample ID and information specifying a compound determined to be contained in the determined sample (hereinafter referred to as a determined compound) are read out. Alternatively, the re-evaluation target sample selection screen may display a list of sample IDs for evaluated samples registered in the evaluation result database 212, and allow the user to select one of them as the sample to be re-evaluated.

[0030] Next, the user performs a predetermined operation on the operation unit 222, whereby a re-evaluation target compound designation screen is displayed on the display unit 221 under the control of the display control unit 203. The re-evaluation target compound designation screen is configured so that the user can designate one or more compounds from among a plurality of compounds registered in the compound library 211, and the user operates the operation unit 222 to designate one or more compounds (hereinafter referred to as re-evaluation target compounds) to be re-evaluated on the screen (step 22). That is, in this step, the display control unit 203, the display unit 221, and the operation unit 222 function as a re-evaluation target compound designation receiving unit in the present invention.

[0031] Next, the undetermined compound identification unit 206 identifies compounds that are not already determined compounds (hereinafter, referred to as undetermined compounds) among the re-evaluation target compounds designated in step 22 (step 23). If there are no undetermined compounds, the display unit 221 displays that fact and ends the series of processes. On the other hand, if there are one or more undetermined compounds, the re-evaluation unit 207 determines whether each of the undetermined compounds was included in the re-evaluation target sample (step 24). Specifically, first, for any of the one or more undetermined compounds identified in step 23, the retention time and peak list of the undetermined compound are read from the compound library 211, and the peak list is compared with the peak list obtained near the retention time among the peak lists of the re-evaluation target sample read in step 21 to obtain the similarity between the two. Then, if the similarity is equal to or greater than a predetermined threshold, it is determined that the undetermined compound was included in the re-evaluation target sample.

[0032] When the above-mentioned judgment is completed for all of the undetermined compounds identified in step 23, a screen showing the judgment result (i.e., whether or not each of the undetermined compounds was contained in the sample to be re-evaluated) is displayed on the display unit 221 under the control of the display control unit 203 (step 25).

[0033] Furthermore, the database registration unit 205 updates the judgment result database 212 by adding information identifying the compound to be re-evaluated and the result of the re-evaluation to the data set stored in the judgment result database 212 in correspondence with the sample ID of the sample to be re-evaluated specified in step 21 (step 26).

[0034] Although the embodiment for carrying out the present invention has been described above with specific examples, the present invention is not limited to the above embodiment, and appropriate modifications are permitted within the scope of the present invention. For example, in the above embodiment, various components in the sample to be determined are separated by a liquid chromatograph (LC section 110) and then introduced into the MS section 120, but instead of a liquid chromatograph, other chromatographs (e.g., gas chromatographs) or separation devices other than chromatographs may be used to separate the sample components. Alternatively, such a separation device may not be provided, and the sample to be determined may be directly introduced into the MS section 120 by the infusion method or the like.

[0035] Furthermore, the mass spectrometry data in the present invention is data representing the intensities of ions in a predetermined m / z range obtained by a scan measurement not involving ion fragmentation, and is not limited to the above-mentioned peak list, and may be, for example, profile data that has not been subjected to peak extraction processing. For example, in the above embodiment, in step 16, the peak list generated for the sample to be determined is associated with the sample ID of the sample to be determined and registered in the determination result database 212, but instead of the peak list, profile data regarding the sample to be determined may be registered.

[0036] In the above embodiment, in the judgment of step 14 and step 24, the peak list of the judgment target sample or the re-judgment target sample (hereinafter sometimes collectively referred to as "target sample") is compared with the peak list of the judgment target compound (or the undetermined compound), and the judgment of whether the judgment target compound (or the undetermined compound) is contained (or was contained) in the target sample is made based on the similarity between the two. Alternatively, the profile data of the target sample may be compared with the profile data of the judgment target compound (or the undetermined compound) registered in advance in the compound library, and the judgment may be made based on the similarity between the two. Alternatively, the m / z of representative ions (hereinafter referred to as representative ions) of various compounds may be registered in the compound library, and the judgment may be made based on whether the peak of the representative ion of the judgment target compound (or the undetermined compound) exists in the profile data or peak list of the target sample.

[0037] Alternatively, the retention time and the m / z of the representative ion for each of the various compounds may be registered in the compound library 211, and in the judgment of steps 14 and 24, the analysis data processing unit 202 may create an extracted ion chromatogram for the representative m / z of each target compound (or undetermined compound) based on the data obtained by the analysis by the analysis unit 100, i.e., three-dimensional data with dimensions of m / z, intensity, and time. In this case, on each extracted ion chromatogram generated for the representative m / z of each target compound, it may be determined whether or not a peak with a predetermined intensity or more exists in a predetermined time range around the retention time of the target compound (or undetermined compound), and if such a peak exists, it may be determined that the target sample contains (or was) the target compound, and if such a peak does not exist, it may be determined that the target sample does not contain (or was) the target compound.

[0038] Alternatively, the compound library 211 may register the retention time, m / z of a plurality of representative ions, and a reference value of the intensity ratio (e.g., peak area ratio or peak height ratio) of the plurality of representative ions for each of the various compounds, and the analysis data processing unit 202 may create extracted ion chromatograms for the m / z of the plurality of representative ions of the target compound (or the undetermined compound) in a predetermined time range around the retention time of the target compound (or the undetermined compound) based on the three-dimensional data, and perform the judgment based on the extracted ion chromatograms (see, for example, Patent Document 2). In this case, first, peak detection is performed for each extracted ion chromatogram, and the intensity value (e.g., area value or height value) of the detected peak is obtained. Then, the intensity ratio of the representative ions in the target sample is calculated from the intensity value of the peak obtained for each extracted ion chromatogram, and this is compared with the reference value of the intensity ratio of the representative ions for the target compound (or the undetermined compound) registered in the compound library 211. If the difference between the two falls within a predetermined tolerance range, it is determined that the target sample contains (or contained) the compound to be determined (or an undetermined compound), and if the difference does not fall within the tolerance range, it is determined that the target sample does not contain (or did not contain) the compound to be determined (or an undetermined compound).

[0039] In the above embodiment, the undetermined compound specifying unit 206 specifies compounds that are not determined compounds among the re-evaluation target compounds specified by the user in step 22, and only the undetermined compounds are subject to judgment (i.e., re-evaluation) in step 24. Instead of providing such an undetermined compound specifying unit 206, the user may not select determined compounds on the re-evaluation target compound specification screen displayed in the above-mentioned step 22. In that case, for example, only compounds other than determined compounds among the compounds registered in the compound library 211 may be displayed on the re-evaluation target compound specification screen, and the user may select a compound to be re-evaluated from among them. Alternatively, all compounds registered in the compound library 211 may be displayed on the re-evaluation target compound display screen, and the user's selection of determined compounds among them may be invalidated.

[0040] Furthermore, regardless of whether or not the compound corresponds to a determined compound, it may be determined whether or not the compound was included in the re-evaluation target sample for all compounds designated by the user as a re-evaluation target compound in step 22. In this case, too, it is desirable to display information specifying the determined compound related to the re-evaluation target sample on the display unit 221 as a reference for the user to designate the re-evaluation target compound (in this case, the display control unit 203 and the display unit 222 function as the determined compound presenting unit in the present invention). EXAMPLES

[0041] Hereinafter, examples of the present invention will be described with reference to Figs. 4 to 8. In this example, first, an extract extracted from an agricultural product (strawberry) was used as a sample to be determined, and it was determined whether or not the 53 types of compounds (pesticides) shown in Figs. 4 and 5 were contained in the sample to be determined. In the determination, the sample to be determined was subjected to a scan analysis using a liquid chromatograph mass spectrometer, and an extracted ion chromatogram for the representative m / z of each compound was created based on the obtained three-dimensional data having dimensions of m / z, intensity, and time. Fig. 6 shows these extracted ion chromatograms superimposed. In each extracted ion chromatogram, a peak appeared near the retention time of the corresponding compound, and it was confirmed that all of the 53 types of compounds were contained in the sample to be determined.

[0042] Thereafter, based on the three-dimensional data that had been saved, an extracted ion chromatogram of the representative m / z of one compound not included in the above 53 types, specifically Aldicarb-sulfone (Aldoxycarb) shown in Figure 7, was created. The extracted ion chromatogram is shown in Figure 8. In this extracted ion chromatogram, a peak appears near the retention time of Aldicarb-sulfone (i.e., 3.282 min), and it was confirmed that the sample to be determined contained Aldicarb-sulfone in addition to the above 53 types of compounds.

[0043] [Aspects] It will be apparent to those skilled in the art that the above-described exemplary embodiments are illustrative of the following aspects.

[0044] (Item 1) A compound determination method by mass spectrometry according to one aspect of the present invention comprises: a mass spectrometry step of acquiring mass spectrometry data by performing a scan measurement on the sample to be determined using a mass spectrometer; a determination step of determining whether or not each of one or more compounds is contained in the target sample based on the mass spectrometry data; a data set creation step of creating a data set in which the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, are associated with information identifying the determination target sample; a database construction step of performing the mass spectrometry step, the determination step, and the data set creation step for each of a plurality of samples as the determination target sample, and constructing a database by accumulating the data sets created for each of the plurality of samples; a re-evaluation step of reading out from the database the data set relating to a sample to be re-evaluated among the plurality of samples, and determining, based on the mass spectrometry data included in the data set, whether or not each of the re-evaluation target compounds, which is one or more compounds including a compound other than the determined compound identified from the data set, is included in the sample to be re-evaluated; It includes.

[0045] In the compound determination method by mass spectrometry according to the first aspect, a sample to be determined is scanned by a mass spectrometer, and based on the results, it is determined whether or not each of one or more compounds to be determined is contained in the sample to be determined. In the scan measurement, mass spectrometry data can be obtained without limiting the compounds to be detected in advance, so that even after the mass analysis and determination are performed, it is possible to determine (re-determine) whether or not a compound that was not expected at the time of the determination is contained in the sample to be determined based on the mass spectrometry data obtained by the scan analysis. Furthermore, in the compound determination method by mass spectrometry according to the first aspect, by storing the mass spectrometry data obtained by scanning and analyzing a plurality of samples respectively and information on the compounds (determined compounds) determined using each mass spectrometry data in a database, the user can easily read out information on the samples that have been determined in the past from the database and perform re-determination.

[0046] (2) The compound determination method by mass spectrometry according to the second aspect of the present invention is the method according to the first aspect of the present invention, In the re-evaluation step, only compounds other than the already-evaluated compounds are selected as the re-evaluation target compounds.

[0047] According to the compound determination method by mass spectrometry relating to paragraph 2, by not subjecting determined compounds to re-evaluation, the load of the calculation process in the re-evaluation can be reduced, and the time required for the re-evaluation can be reduced.

[0048] (Item 3) The method for determining a compound by mass spectrometry according to Item 3 is the method according to Item 1 or 2, further comprising: The mass resolution of the mass spectrometer is 10,000 or more.

[0049] According to the compound determination method by mass spectrometry relating to paragraph 3, by performing the above-mentioned scan measurement with high mass resolution, it is possible to realize highly accurate compound determination (and re-determination) with little influence of impurity components in the sample.

[0050] (4) The compound determination system by mass spectrometry according to the fourth aspect of the present invention comprises: a determination unit that determines whether or not each of one or more compounds is contained in a target sample based on mass spectrometry data obtained by performing a scan measurement on the target sample using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, in a database in association with information identifying the determination target sample; a re-evaluation target sample designation receiving unit for receiving, from a user, designation of a sample to be re-evaluated from among a plurality of evaluation target samples registered in the database; a re-evaluation target compound designation receiving unit that receives, from a user, designation of a re-evaluation target compound, which is one or more compounds to be re-evaluated; an undetermined compound identification unit that reads out from the database information identifying the determined compounds stored for the sample to be re-evaluated, and identifies undetermined compounds that are not included in the determined compounds among the compounds to be re-evaluated; a re-evaluation unit that reads out the mass spectrometry data stored for the sample to be re-evaluated from the database and determines whether or not each of the undetermined compounds was contained in the sample to be re-evaluated based on the mass spectrometry data; It has the following characteristics.

[0051] According to the compound determination system by mass spectrometry according to paragraph 4, when re-evaluating a sample previously determined, if a compound already determined is included among the compounds specified by the user, the compound can be automatically excluded from the target of re-evaluation. This makes it possible to avoid re-evaluating a compound that has already been determined, thereby reducing the load of the calculation process in the re-evaluation and reducing the time required for the re-evaluation.

[0052] (5) The compound determination system by mass spectrometry according to the 5th paragraph, a determination unit that determines whether or not each of one or more compounds is contained in a target sample based on mass spectrometry data obtained by performing a scan measurement on the target sample using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, in a database in association with information identifying the determination target sample; a re-evaluation target sample designation receiving unit for receiving, from a user, designation of a sample to be re-evaluated from among a plurality of evaluation target samples registered in the database; a re-evaluation target compound designation receiving unit that receives, from a user, designation of a re-evaluation target compound, which is one or more compounds to be re-evaluated; a re-evaluation unit that reads out the mass spectrometry data stored for the sample to be re-evaluated from the database, and determines whether or not each of the compounds to be re-evaluated is contained in the sample to be re-evaluated based on the mass spectrometry data; having The re-evaluation target compound designation receiving unit reads out from the database information identifying the determined compound stored for the sample to be re-evaluated, and prevents the user from designating the determined compound as the compound to be re-evaluated.

[0053] According to the compound determination system by mass spectrometry according to paragraph 5, when re-evaluating a sample that has been previously determined, it is possible to prevent a compound that has already been determined from being designated as a target for re-evaluation. This makes it possible to avoid re-evaluating a compound that has already been determined, thereby reducing the load of the calculation process in the re-evaluation and reducing the time required for the re-evaluation.

[0054] (6) The compound determination system by mass spectrometry according to the 6th paragraph, a determination unit that determines whether or not each of one or more compounds is contained in a target sample based on mass spectrometry data obtained by performing a scan measurement on the target sample using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the determined compound, which is the one or more compounds, in a database in association with information identifying the determination target sample; a re-evaluation target sample designation receiving unit for receiving, from a user, designation of a sample to be re-evaluated from among the plurality of evaluation target samples registered in the database; a determined compound presenting unit that reads out information for identifying the determined compound stored in the sample to be re-evaluated from the database and presents the information to a user; a re-evaluation target compound designation receiving unit for receiving designation of re-evaluation target compounds, which are one or more compounds to be re-evaluated, from a user; a re-evaluation unit that reads out the mass spectrometry data stored for the sample to be re-evaluated from the database, and determines whether or not each of the compounds to be re-evaluated is contained in the sample to be re-evaluated based on the mass spectrometry data; It has the following characteristics.

[0055] According to the compound determination system using mass spectrometry relating to paragraph 6, when re-evaluating a sample that has been previously determined, information on compounds that have already been determined to be contained in the sample or not is presented to the user, so that the user can refer to the information and easily specify the compound to be re-evaluated. [Explanation of symbols]

[0056] 100…Analysis Department 110...LC section 120…MS Department 200...Control / processing section 201...Analysis control unit 202...Analysis data processing section 203...Display control unit 204...Judgment section 205…Database Registration Department 206...Unidentified compound identification section 207...Rejudgment Department 211…Compound Library 212…Judgment result database 221...Display section 222...Operation unit

Claims

1. a mass spectrometry step of acquiring mass spectrometry data by performing a scan measurement over a predetermined m / z range on the sample to be evaluated using a mass spectrometer; a determination step of determining whether or not each of one or more compounds is contained in the target sample based on the mass spectrometry data; a data set creation step of creating a data set in which the mass spectrometry data and information identifying the one or more determined compounds are associated with information identifying the sample to be determined; a database construction step of performing the mass spectrometry step, the determination step, and the dataset creation step for each of a plurality of samples as the determination target sample, and constructing a database by accumulating the datasets created for each of the plurality of samples; a re-evaluation step of reading out from the database the dataset relating to a sample to be re-evaluated among the plurality of samples, and determining, based on the mass spectrometry data included in the dataset, whether or not each of the re-evaluation target compounds, which is one or more compounds including a compound other than the determined compound identified from the dataset, was contained in the sample to be re-evaluated; A compound determination method by mass spectrometry comprising:

2. In the re-evaluation step, only compounds other than the already-evaluated compounds are selected as the re-evaluation target compounds. The compound determination method by mass spectrometry according to claim 1 .

3. The mass resolution of the mass spectrometer is 10,000 or more. The compound determination method by mass spectrometry according to claim 1 or 2.

4. a determination unit that determines whether or not each of one or more compounds is contained in the target sample based on mass spectrometry data obtained by performing a scan measurement of the target sample over a predetermined m / z range using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the one or more determined compounds in a database in association with information identifying the sample to be determined; a reassessment target sample designation receiving unit that receives, from a user, designation of a sample to be reassessed from among a plurality of assessment target samples registered in the database; a re-evaluation target compound designation receiving unit that receives, from a user, designation of one or more compounds to be re-evaluated; an undetermined compound identifying unit that reads out from the database information identifying the determined compounds stored for the sample to be re-evaluated, and identifies undetermined compounds that are compounds not included in the determined compounds among the compounds to be re-evaluated; a re-evaluation unit that reads out the mass spectrometry data stored for the sample to be re-evaluated from the database and determines whether or not each of the undetermined compounds was contained in the sample to be re-evaluated based on the mass spectrometry data; A compound determination system using mass spectrometry.

5. a determination unit that determines whether or not each of one or more compounds is contained in the target sample based on mass spectrometry data obtained by performing a scan measurement of the target sample over a predetermined m / z range using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the one or more determined compounds in a database in association with information identifying the sample to be determined; a reassessment target sample designation receiving unit that receives, from a user, designation of a sample to be reassessed from among a plurality of assessment target samples registered in the database; a re-evaluation target compound designation receiving unit that receives, from a user, designation of one or more compounds to be re-evaluated; a redetermination unit that reads out the mass spectrometry data stored for the sample to be redeterminated from the database and determines whether or not each of the compounds to be redeterminated was contained in the sample to be redeterminated based on the mass spectrometry data; and the re-evaluation target compound designation receiving unit reads out, from the database, information specifying the determined compound stored for the sample to be re-evaluated, and prevents the user from designating the determined compound as the re-evaluation target compound. Compound identification system using mass spectrometry.

6. a determination unit that determines whether or not each of one or more compounds is contained in the target sample based on mass spectrometry data obtained by performing a scan measurement of the target sample over a predetermined m / z range using a mass spectrometer; a database registration unit that stores the mass spectrometry data and information identifying the one or more determined compounds in a database in association with information identifying the sample to be determined; a reassessment target sample designation receiving unit that receives, from a user, designation of a sample to be reassessed from among the plurality of assessment target samples registered in the database; a determined compound presenting unit that reads out, from the database, information specifying the determined compound stored for the sample to be re-evaluated, and presents the information to a user; a re-evaluation target compound designation receiving unit that receives, from a user, designation of one or more compounds to be re-evaluated; a redetermination unit that reads out the mass spectrometry data stored for the sample to be redeterminated from the database and determines whether or not each of the compounds to be redeterminated was contained in the sample to be redeterminated based on the mass spectrometry data; A compound determination system using mass spectrometry.

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