Sample analysis assist device

Abstract

A sample analysis assistance device (20) is provided with: a storage unit (21) that stores information in which information for identifying a plurality of known compounds is associated with analysis conditions for the compounds, for each of the known compounds; a display unit (26); a compound list input reception unit (221) that receives an input of a list of information for identifying one or more compounds to be analyzed; an analysis condition reading unit (222) that refers to the information stored in the storage unit and reads, from the storage unit, the analysis conditions of the compounds corresponding to each of the information for identifying one or more compounds to be analyzed described in the list received by the compound list input reception unit; and an analysis condition display unit (223) that displays, on the display unit, the analysis conditions of the one or more compounds read by the analysis condition reading unit.

Description

Technical Field

[0001] This invention relates to an auxiliary device for sample analysis. Background Technology

[0002] When storing, transporting, and handling pharmaceuticals, packaging paper or containers are used. Furthermore, medical devices are used when administering pharmaceuticals to patients. During these processes, if eluents or leachates from the containers used to store the pharmaceuticals or the medical devices used to administer them (hereinafter collectively referred to as "pharmaceuticals") become contaminated with the pharmaceuticals, the effectiveness of the pharmaceuticals may be compromised or health hazards may be caused. Therefore, it is recommended to conduct eluent or leachate testing (E&L testing) on ​​pharmaceuticals. In E&L testing of pharmaceuticals, gas chromatography-mass spectrometry (GC-MS) is used, for example (e.g., Non-Patent Literature 1). Previously, when performing E&L testing using GC-MS, non-target analysis was typically performed using scanning methods. Recently, the following method has also been used: utilizing a database that includes various known compounds and the analytical conditions of each compound in a gas chromatography-mass spectrometry instrument, and displaying a list of the known compounds included therein on the screen, the analytical conditions of each analytical compound are extracted by selecting the compound to be analyzed from it (e.g., non-patent literature 2, 3).

[0003] Existing technical documents

[0004] Non-patent literature

[0005] Non-patent document 1: "Evaluation of Eluates from Medical Device Containers (E&L)", [online], Shimadzu Corporation, [September 15, 2023], Shimadzu Corporation<URL:https: / / www.shimadzu-techno.co.jp / annai / pha / h09.html>

[0006] Non - Patent Document 2: Piet Christiaens, Jean - Marie Beusen, Philippe Verlinde, et al., “Identifying and Mitigating Errors in Screening for Organic Extractables and Leachables: Part 1; Introduction to Errors in Chromatographic Screening for Organic Extractables and Leachables and Discussion of the Errors of Omission”, PDA J. Pharm Sci. and Tech. 2020, 7490 - 107

[0007] Non - Patent Document 3: Dennis Jenke and Alex Odufu, “Utilization of Internal Standard Response Factors to Estimate the Concentration of Organic Compounds Leached from Pharmaceutical Packaging Systems and Application of Such Estimated Concentrations to Safety Assessment”, Journal of Chromatographic Science 2012;50:206 - 212, doi:10.1093 / chromsci / bmr048 Summary of the Invention

[0008] Problems to be Solved by the Invention

[0009] The purpose of E&L testing for pharmaceutical products is to assess the risks posed by impurities inherent in the product itself or by compounds that may have been introduced from the manufacturing process. Guidelines for E&L testing recommend compiling a list of compounds that may be present in the pharmaceutical product to be tested before conducting the test, prioritizing compounds with a higher risk of health hazards. Compound databases contain information on a large number (e.g., hundreds) of compounds found in a wide variety of pharmaceutical products. Therefore, searching and selecting the target compound from a large list of compounds displayed on the screen, and extracting the analytical conditions for each target compound, is time-consuming and labor-intensive.

[0010] The problem this invention aims to solve is to reduce the burden of extracting analytical conditions for the target compound from a large number of analytical conditions of known compounds collected in a database.

[0011] Solution for solving the problem

[0012] The sample analysis auxiliary device according to the present invention, made to solve the above problems, comprises:

[0013] The storage unit stores information corresponding to the analytical conditions for identifying the compound for each of a plurality of known compounds.

[0014] Display section;

[0015] The compound list input receiving unit receives an input of a list of information used to identify one or more analyte compounds;

[0016] An analysis condition reading unit, referring to information stored in the storage unit, reads from the storage unit the analysis conditions of compounds corresponding to each piece of information in the list received by the compound list input receiving unit for identifying one or more analyte compounds; and

[0017] An analysis condition display unit displays the analysis conditions of one or more compounds read by the analysis condition reading unit.

[0018] Invention Effects

[0019] In the sample analysis auxiliary device according to the present invention, the user only needs to input a list of information for identifying one or more analyte compounds as the target of analysis. The analysis condition reading unit then reads the analysis conditions of the compounds corresponding to each piece of information in the input list for identifying one or more analyte compounds from the analysis conditions of multiple known compounds stored in the storage unit, and the analysis condition display unit displays the analysis conditions of each compound on the display unit. Therefore, the burden of extracting the analysis conditions of the target compounds from a large number of known compound analysis conditions stored in a database can be reduced. Attached Figure Description

[0020] Figure 1 This is a structural diagram of the main parts of a gas chromatography-mass spectrometry system including the sample analysis auxiliary device according to the present invention.

[0021] Figure 2 This is an example of the compound list input screen in this embodiment.

[0022] Figure 3 This is an example of a keyword input screen in this embodiment.

[0023] Figure 4 This is an example of the analysis condition list display screen in this embodiment.

[0024] Figure 5 This is an example of grouping the compounds and setting the measurement time range through initial settings in this embodiment.

[0025] Figure 6 This is an example in this embodiment of changing the measurement time range by splitting an initially set group into two. Detailed Implementation

[0026] The embodiments of the sample analysis auxiliary device according to the present invention will now be described with reference to the accompanying drawings.

[0027] Figure 1 The main structural components of the gas chromatography-mass spectrometry (GC-MS) system 1, which includes the sample analysis auxiliary device of this embodiment, are shown. The GC-MS system 1 of this embodiment is used, for example, to perform tests (E&L tests) on eluents or leachates from containers holding pharmaceuticals or medical devices for administering pharmaceuticals (hereinafter collectively referred to as "medical supplies"). These medical supplies include primary materials such as packaging materials that directly contact the pharmaceuticals, and secondary materials such as cardboard boxes that indirectly contact the pharmaceuticals.

[0028] The gas chromatography-mass spectrometry system 1 includes a gas chromatography-mass spectrometry analysis unit (GC-MS) 10 as the determination unit and a control / processing unit 20. The control / processing unit 20 corresponds to the sample analysis auxiliary device according to the present invention.

[0029] The gas chromatography-mass spectrometry (GC-MS) analysis unit 10 is a combination of a gas chromatograph for separating various compounds contained in a sample and a mass spectrometry analysis unit for sequentially analyzing the compounds separated by the gas chromatograph. In this embodiment, the mass spectrometry analysis unit employs a structure capable of performing both MS and MS / MS measurements (such as a triple quadrupole mass spectrometer, an ion trap-time-of-flight mass spectrometer, etc.). In this embodiment, a device with this structure is used to perform MRM measurements and product ion scanning measurements in addition to SIM and scanning measurements; however, a single quadrupole mass spectrometer or similar device can also be used when only SIM and / or scanning measurements are performed.

[0030] The control / processing unit 20 includes a storage unit 21. The storage unit 21 stores a compound database (compound DB) 211. The compound database 211 contains information on a large number (e.g., hundreds) of known compounds that may be included in various pharmaceutical products. This information includes, in addition to identification numbers (IDs) in the database, specific information about the compound, information on measurement conditions, information on analytical conditions, and supplementary information. In this specification, the measurement conditions and analytical conditions of the compound are collectively referred to as analytical conditions.

[0031] Specific information about a compound may include, for example, the compound name, CAS number, PubChem ID, chemical formula, and structural formula. Information regarding the compound's assay conditions may include, for example, the type and temperature of the column used in the gas chromatograph for the determination of the compound, the type and flow rate of the carrier gas, the retention index and retention time of each column; and information on the mass spectrometry analysis mode (SIM assay, scanning assay, MRM assay, product ion scanning assay, etc.) and the mass-to-charge ratio of the ions (mass-to-charge ratio of the monitor ion in SIM assay, range of mass-to-charge ratio in scanning assay, mass-to-charge ratio of the MRM transition (precursor ion and product ion) in MRM assay, and range of mass-to-charge ratio of the precursor ion and product ion in MS / MS assay, etc.). Information regarding the compound's resolution conditions may include, for example, mass spectrometry, product ion spectrum, baseline values ​​for the intensity ratio of the quantitative ion to the confirming ion, baseline values ​​for the intensity ratio of the quantitative MRM transition to the confirming MRM transition, standard curve, limit of quantitation (LOQ), and limit of detection (LOD). Supplementary information includes keywords related to each compound. Specifically, this could include, for example, the category of products that may contain the compounds (injector cartridges, syringes, packaging paper, etc.), the manufacturing equipment, manufacturing plant, manufacturer, etc., where the compounds may be introduced during the manufacturing process.

[0032] The control / processing unit 20 includes the following functional modules: a compound list input receiving unit 221, an analytical condition reading unit 222, an analytical condition display unit 223, an analytical execution document creation unit 224, an analytical control unit 225, and an analysis processing unit 226. The control / processing unit 20 is essentially a personal computer, and it executes pre-installed software (sample analysis auxiliary program 22) via a processor to implement the aforementioned functional modules. Furthermore, the control / processing unit 20 is connected to an input unit 25 and a display unit 26. The sample analysis auxiliary program 22 can be executed in a normal user mode where login is possible without an ID or password, and in an administrator mode where login is possible using an ID and password with pre-defined permissions.

[0033] Next, the steps for E&L testing of pharmaceutical products using the gas chromatography-mass spectrometry system of this embodiment will be described.

[0034] When the user instructs the analysis to be performed, the compound list input receiving unit 221 displays a screen on the display unit 26 allowing the user to input a list of compounds to be analyzed. This screen can be, for example, a table-style screen with columns for inputting compound names, CAS numbers, or PubChem IDs, and columns displaying the type of columns that can be used to determine compounds corresponding to the input compound names, CAS numbers, or PubChem IDs.

[0035] Figure 2 An example screen is shown for inputting a list of compounds to be analyzed. The screen displays a compound list display bar 31, a keyword input button 32, a search button 33, a column selection button 34, a mass spectrometry analysis mode selection button 35, and an OK button 36. The compound list display bar 31 includes a compound name input bar 311, a CAS number input bar 312, a PubChem ID input bar 313, and a corresponding column display bar 314.

[0036] If a user enters a compound name, CAS number, or PubChem ID in any of the three input fields (compound name input field 311, CAS number input field 312, and PubChem ID input field 313) for each analyte compound and presses the search button 33, the compound list input receiving unit 221 will check against the compound-specific information stored in the compound database 211 to determine if data with the entered compound name, CAS number, or PubChem ID exists. Then, if data with the entered compound name, CAS number, or PubChem ID exists in the compound database 211, the type of column suitable for the compound's determination will be identified based on the compound's assay conditions. In this embodiment, there are four types of columns (column A to column D), but the number of columns displayed varies depending on the number of columns registered in the compound database 211. For each input analyte compound, the compound list input receiving unit 221 will display "○" in the column display field if the column can be used. Furthermore, the number of compounds displayed in the compound list display field 31 can be appropriately changed through a predetermined operation performed via the input unit 25. Alternatively, the number can be automatically incremented line by line whenever the user enters a compound name, CAS number, or PubChem ID in any of the compound name input field 311, CAS number input field 312, or PubChem ID input field 313.

[0037] This section illustrates an example of a user directly entering a compound name, CAS number, or PubChem ID in any of the three input fields: Compound Name Input Field 311, CAS Number Input Field 312, and PubChem ID Input Field 313. However, if a compound list containing compound names, CAS numbers, or PubChem IDs has been pre-created and saved in storage unit 21, the compound name can be entered by reading that file. Specifically, for example, the user can open the location where the file containing the compound list is saved and drag and drop the file onto the compound list display field 31 to read the compound list contained in that file.

[0038] If a compound corresponding to the compound name, CAS number, or PubChem ID entered by the user is not registered in the compound database 211, the compound list input receiving unit 221 notifies the display unit 26 on the screen that the compound corresponding to the information entered by the user is not saved in the compound database 211. Then, it asks the user whether to add the compound to the compound database 211.

[0039] If the user instructs the user to add the compound to the compound database 211, another pop-up window will appear, allowing the user to enter the information required for registration in the compound database 211 (specific information about the compound, analytical conditions, and supplementary information). If the user enters the required items, a new identification number (ID) will be assigned and the compound will be registered in the compound database 211.

[0040] Furthermore, users can input keywords along with the compounds they are analyzing, either individually or in a list format. For example, if a user inputs these compounds for an E&L test on pharmaceutical product a manufactured by Pharmaceutical A, and simultaneously inputs keywords such as "Pharmaceutical A" or "Pharmaceutical product a," then this information will be added to the compound database 211 as supplementary information for each compound entered by the user. By pre-adding supplementary information in this way, when conducting an E&L test again on the same pharmaceutical product that has undergone E&L testing in the past, multiple compounds can be entered at once simply by inputting keywords as described below.

[0041] Users can not only enter compound names, CAS numbers, or PubChem IDs—information used to identify a compound—but also create lists of compounds by entering information to identify multiple compounds simultaneously. Figure 2 In the example shown, when the user presses the keyword input button 32, the following will be displayed: Figure 3 The keyword input screen shown initially displays only one keyword input field 38 and an OK button 39. When the user enters a keyword in the first keyword input field 38, a next keyword input field 38 is automatically added below it. Therefore, the user can enter any number of keywords. When the user enters a keyword in the keyword input field 38 and presses the OK button 39, the compound list input receiving unit 221 checks the supplementary information of the compounds stored in the compound database 211. It then reads in batches all compounds whose input keywords are registered as supplementary information from the compound database 211 and inputs the same information into the compound name input field 311, CAS number input field 312, PubChem ID input field 313, and corresponding column display field 314. In this example, a so-called AND search containing all the input keywords is performed, but a so-called OR search can also be performed to read in batches compounds containing any one of the input keywords from the compound database 211.

[0042] The user confirms the display of the corresponding column display bar 314 and operates the column selection button 34 to select any column that can be used for all analyte compounds. The column selection button 34 is a drop-down menu, allowing selection only of columns suitable for all analyte compounds. Figure 2 In the example shown, column A or column B can be selected via the drop-down menu of column selection button 34. Then, the mass spectrometry analysis mode selection button 35 is used to select the mass spectrometry analysis mode for each analyte compound. Mass spectrometry analysis mode selection button 35 is also a drop-down menu, allowing selection of any of the following: scan assay, SIM assay, product ion scan assay, and MRM assay.

[0043] When the user selects the column type and mass spectrometry analysis mode and presses the OK button 36, the compound list input receiving unit 221 identifies the compound displayed at this time point in the compound list display bar 31 as a provisional analyte compound. When multiple column types and / or mass spectrometry analysis modes are used for the analyte compounds, simply perform the operation of creating a compound list of analyte compounds with the same combination of column type and mass spectrometry analysis mode as the number of combinations of column type and mass spectrometry analysis mode, and then press the OK button 36.

[0044] Subsequently, the analysis condition reading unit 222 reads the measurement conditions, etc., related to the type of column selected by the user via the column selection button 34 and the mass spectrometry analysis mode selected via the mass spectrometry analysis mode selection button 35, from the compound database 211 for each analytical target compound determined by the compound list input receiving unit 221.

[0045] When the analytical condition reading unit 222 reads the measurement conditions of each analyte compound, the analytical condition display unit 223 displays the read information in tabular form on the display unit 26.

[0046] Figure 4 An example of a list of analytical conditions is shown. The screen displays an analytical conditions list display bar 41 and an OK button 42. The analytical conditions list display bar 41 displays the serial number, type, assay mode, limit of quantitation, method number, compound name, retention index, retention time, and CAS number for each analyte compound determined by the compound list input receiving unit 221. These item bars are equipped with filter buttons, which can be used to rearrange the list or narrow down the displayed items. The items displayed in the analytical conditions list display bar 41 can be appropriately modified, for example, by an administrator using an ID and password granted administrator privileges to execute sample analysis assistance procedures.

[0047] The serial number field displays the identification number (ID) of the compound in the compound database 211. The type field indicates whether the user has selected the compound as the final target compound for analysis. At the point when the list of analytical conditions is initially displayed on the analytical conditions display unit 223, the analytical conditions for the provisional target compounds are displayed, and the type field for all compounds is displayed as "Target".

[0048] The measurement mode bar is displayed Figure 2 The screen shown displays the mass spectrometry analysis mode selected by the user through the mass spectrometry analysis mode selection button 35. The limit of quantitation (LOQ) column displays the LQ value of the compound listed in the compound database 211. The method number column displays the analyte compounds analyzed in a single assay, each with the same number. Figure 4 In the examples, all values ​​are displayed as "1". The determination conditions for these analyte compounds are written into a method file (analysis execution file) and determined in one go. The retention index and retention time columns display the retention index and retention time of the compound as recorded in compound database 211. Although Figure 4 The example display does not include this, but a supplementary information bar can be further displayed in the analysis condition list display bar 41. In this case, the supplementary information bar displays supplementary information about the compound included in the compound database 211.

[0049] exist Figure 4 In the image shown, it can be confirmed that... Figure 2 The screen displayed shows the specific assay conditions or limit of quantitation (LOQ) values ​​for the compound that the user has temporarily selected as the target compound for analysis. If the user determines that, for example, the displayed assay conditions or LOQ values ​​are unsuitable, they can exclude the compound from the target compounds by switching the type field from "Target" to blank. The excluded compound can then be analyzed using other assay methods.

[0050] Figure 4 The display example is in Figure 2 The displayed screen shows the compounds morpholine and 3-methyl-2(5H)-furanone excluded from the list of analyte compounds by the user. Even if a compound is temporarily excluded, it will be reselected as an analyte compound if the user selects "Target" by clicking on the compound's type field.

[0051] Among the compounds identified as provisional analytical targets, there may be compounds not listed in compound database 211 that the user has not yet registered with. Figure 2 The selected mass spectrometry analysis mode and determination conditions for the compound are shown on the screen. In this case, Figure 4 The list of analytical conditions shows compounds for which the analytical mode selected by the user is not included in the analysis conditions highlighted (color display, flashing display, etc.), prompting the user to change the mass spectrometry analysis mode (change the settings in the determination mode bar) or exclude them from the analytical target compounds (exclude them from the "target" in the type bar).

[0052] Furthermore, when a user executes the sample analysis auxiliary procedure 22 using an ID and password granted administrator privileges, they can... Figure 4 The list of analytical conditions shown can be edited (added, modified, or deleted) for items other than the compound name, CAS number, and PubChem ID, which are constant information. For example, the assay conditions read from compound database 211 can be changed. Alternatively, supplementary information shared by multiple compounds can be added to this screen. Therefore, the next time a list of analytical compounds is created, the added supplementary information can be used as keywords to batch input compounds included in the current list. Furthermore, the supplementary information, including product category and manufacturing apparatus, can be updated appropriately to reflect updates to the pharmaceutical products being processed.

[0053] exist Figure 4 In the list of analytical conditions shown, if multiple compounds with similar retention times are selected, and the initial setting is directly set to the length of time for performing a single mass spectrometry analysis of each compound (dwell time), the time interval between mass spectrometry analyses of each compound (loop time) may become too long. For example, in SIM or MRM assays, after the assay is completed, the peak shape of the mass chromatogram is determined based on the intensity values ​​of multiple measurements performed at the retention times of each compound, and the compound is quantified based on the area (or height) of that peak. In this case, if the loop time is too long, the number of measurement points may be insufficient, and the correct peak shape may not be obtained, resulting in a decrease in the accuracy of the quantification. To address this situation, the loop time is fixed at a constant value in this embodiment. This loop time is preset to the length of the peak of each compound in the chromatogram that can be formed by more than the required number of measurement points (e.g., 10 points) (in other words, a length less than the time obtained by dividing the time for measuring each compound separated by the gas chromatograph column by the required number of measurement points (e.g., 10 points)). When a user sets a request processing time (including using the initial request processing time directly), the determination time for each compound is set accordingly, and the residence time is determined. The request processing time refers to the minimum length of the determination time centered on the retention time (or retention index) of each compound (minimum determination time). For example, if the request processing time is set to 0.3 min, the determination time range for each compound is set so that each compound is determined within a time period of at least ±0.3 min centered on the retention time.

[0054] In this embodiment, during display Figure 4The time points in the analysis condition list shown, or the time points when users with administrator privileges changed the measurement conditions, are displayed on the display unit 26 as follows: Figure 5 The image shown. Figure 5 The screen shown arranges the measurement times of each compound vertically, with the measurement time on the horizontal axis. In the initial settings, such as... Figure 5 As shown, one or more compounds whose set measurement times overlap in time, determined based on the user-set request processing time, are grouped. Within each group, the residence time is calculated by dividing the fixed cycle time by the number of analyte ions (analyte ions for SIM analysis, and analyte MRM transitions for MRM analysis, hereinafter referred to as analyte ions) used for the analysis of the compounds included in that group. In this example, compounds A through C are grouped into one group (Group 1), and compounds D through H are grouped into another group (Group 2). Within each group, an actual measurement time range is set to cover the set measurement times of all compounds, and the compounds are measured sequentially within this actual measurement time range.

[0055] When the number of compounds in each group is small, the initial setup described above allocates sufficient residence time to each compound. However, if the number of analytes used to analyze the compounds in a group increases, it may be impossible to allocate sufficient residence time to each analyte corresponding to the compounds in that group. Therefore, it is preferable to configure the group to be highlighted when the residence time allocated to each analyte is less than a predetermined time. Figure 5 (Used in thick dashed lines) to prompt the user to confirm.

[0056] The user confirms the residence time assigned to each analyte ion for each compound included in the highlighted group. If the residence time is deemed insufficient, the user enters an instruction to split the group. When the user instructs the user to split the group, the specified group is divided into two. At this point, the set measurement time for at least one compound will cross the boundary between the two groups. The analyte ions of the compounds whose set measurement times cross the group boundary are measured in both groups. Figure 6 The example shown is to Figure 5 In the example of group 2 being divided, compounds D to K are divided into group 2-1 containing compounds D to H and group 2-2 containing compounds H to K. Compound H, whose measurement time crosses the boundary between these two groups, is measured in both groups. Thus, even when there are many compounds with similar retention times and a large number of analyte ions of these compounds, sufficient residence time can be allocated to each analyte ion, and even when a compound is measured in multiple groups, the cycle time can be kept constant.

[0057] exist Figure 4In the displayed screen, when the user presses the OK button 42, the compound displayed as "Target" in the type field at this time point is set as the final analyte compound. The analysis execution file creation unit 224 creates an analysis execution file for each final determined analyte compound, specifying the measurement conditions for performing the mass spectrometry analysis mode selected in the measurement mode field. Furthermore, if the user modifies information read from the compound database 211, the user is prompted whether to reflect the change in the compound database 211. When the user instructs to reflect the information, the modified content is saved in the compound database 211.

[0058] If, after preparing the analytical execution document, the user places the analyte sample and starts the measurement by issuing a predetermined operation instruction via the input unit 25, the analytical control unit 225 will measure each analyte compound using the measurement conditions described in the analytical execution document.

[0059] Each compound in the sample introduced into the gas chromatography-mass spectrometry analysis unit 10 is separated by the column of the gas chromatograph, and elutes from the column at its retention time for mass spectrometry analysis. In the mass spectrometry analysis unit, scans are repeatedly performed within a predetermined width centered on the retention time (or retention index) of each analyte compound. The data acquired during the measurements are sequentially stored in the storage unit 21.

[0060] After the measurement is completed, the analysis processing unit 226 reads the measurement data stored in the storage unit 21 and performs analysis processing. In this example, since mass spectra of each analyte compound are obtained by scanning and measuring, the analysis processing unit 226 reads the mass spectra of each analyte compound from the compound database 211 and calculates its consistency with the mass spectra obtained by measurement (e.g., consistency of mass-to-charge ratio and normalized intensity of mass peaks). Then, if the consistency exceeds a predetermined threshold, it is determined that the sample contains the compound. Furthermore, the compound is quantified by comparing the mass peak intensity of the target ion appearing in the mass spectrum with a standard curve.

[0061] This section describes the case of scanning determination. However, in the case of SIM determination, the analysis processing unit 226 reads a reference value for the intensity ratio of quantitative ions to confirmatory ions from the compound database 211. Based on the fact that the difference between the intensity ratio of quantitative ions and confirmatory ions obtained through measurement and the reference value is within a predetermined range, it determines whether the sample contains the analyte compound. If the compound is contained, the compound is further quantified by comparing the measured intensity of the quantitative ions with a standard curve. In the case of product ion scanning determination, the analysis processing unit 226 reads the product ion spectrum of each analyte compound from the compound database 211 and calculates its consistency with the product ion spectrum obtained through measurement (e.g., consistency of mass-to-charge ratio and normalized intensity of the mass peak). Then, if the consistency exceeds a predetermined threshold, it is determined that the sample contains the compound. Furthermore, the compound is quantified by comparing the intensity of the mass peak of the target ion (product ion) appearing in the product ion spectrum with a standard curve.

[0062] In E&L testing of pharmaceutical products, non-target analyses are typically performed. In non-target analyses, a scanning assay is performed without pre-setting the analyte compound, and a mass spectrometer is obtained. The obtained mass spectra are then compared with the mass spectra of known compounds stored in a library, and candidate compounds are listed in descending order of consistency.

[0063] However, because the library contains mass spectra of a large number of known compounds, it lists a large number of compounds with the same degree of consistency, making it sometimes difficult to determine which one is included in the actual sample.

[0064] In E&L testing of pharmaceutical products, it is particularly preferred to analyze in detail compounds that pose a high risk of health hazards, such as impurities contained in the pharmaceutical product itself or compounds that may have been introduced from the manufacturing equipment and eluted into the pharmaceutical product. In other words, for these compounds, it is preferable to use a more selective assay method for E&L testing.

[0065] Therefore, target analysis is effective in which compounds with a high risk of contamination with pharmaceuticals and potential health hazards due to elution from pharmaceuticals are pre-specified and analyzed. In target analysis, target compounds are selected from a large database of known compounds, and the obtained mass spectrometry or product ion spectra are compared with those of known compounds in the database to determine the degree of agreement. Therefore, unlike conventional E&L tests using a library, which list a large number of candidate compounds with similar agreement, it is easier to determine whether the sample contains the desired compound. Furthermore, in target analysis, sometimes SIM or MRM assays, which have higher selectivity than scanning assays or product ion scanning assays, are performed to determine whether the compound is present and (if present) its concentration.

[0066] However, compound databases contain information on a large number (e.g., hundreds) of compounds included in a wide variety of pharmaceutical products. Therefore, searching for and selecting the target compound from the large list of compounds displayed on the screen, and extracting the analytical conditions for that compound, is a time-consuming and laborious task.

[0067] In this regard, in the gas chromatography-mass spectrometry system 1 of this embodiment, for example, in... Figure 2 On the screen shown, the user simply inputs a list of information for identifying one or more target compounds. The analysis condition reading unit 222 then reads the analysis conditions of the compounds corresponding to the information in the input list for identifying one or more target compounds from the analysis conditions of multiple known compounds stored in the compound database 211. The analysis condition display unit 223 then displays the analysis conditions of each compound on the display unit 26. Therefore, the burden of extracting the analysis conditions of the target compounds from the large number of analysis conditions of known compounds collected in the compound database 211 can be reduced.

[0068] The above implementation is an example and can be appropriately modified according to the spirit of the present invention.

[0069] Although the above embodiment is a gas chromatography-mass spectrometry system 1, the same structure can be used in analytical systems equipped with other analytical devices. Furthermore, although the above embodiment is configured for E&L testing of pharmaceutical products, the same structure can be used in other analyses. For example, in the above embodiment, as supplementary information for compounds included in the compound database 211, information related to pharmaceutical E&L testing is shown; however, any information can be registered in the supplementary information, but it is preferable to register appropriate information corresponding to the characteristics of the analyte, the purpose of the analysis, and the analytical method.

[0070] The display screens in the above embodiments are all examples, and the display method can be changed appropriately.

[0071] [Way]

[0072] It will be apparent to those skilled in the art that the above exemplary embodiments are specific examples of the following approaches.

[0073] (Item 1)

[0074] One embodiment of the sample analysis auxiliary device of the present invention comprises:

[0075] The storage unit stores information corresponding to the analytical conditions for identifying the compound for each of a plurality of known compounds.

[0076] Display section;

[0077] The compound list input receiving unit receives an input of a list of information used to identify one or more analyte compounds;

[0078] An analysis condition reading unit, referring to information stored in the storage unit, reads from the storage unit the analysis conditions of compounds corresponding to each piece of information in the list received by the compound list input receiving unit for identifying one or more analyte compounds; and

[0079] An analysis condition display unit displays the analysis conditions of one or more compounds read by the analysis condition reading unit.

[0080] In the sample analysis auxiliary device described in item 1, the user only needs to input a list of information for identifying one or more analyte compounds. The analysis condition display unit then retrieves the analysis conditions of compounds corresponding to each piece of information in the input list for identifying one or more analyte compounds from the analysis conditions of multiple known compounds stored in the storage unit, and displays the analysis conditions of each compound on the display unit. Therefore, the burden of extracting the analysis conditions of analyte compounds from a large number of known compound analysis conditions stored in a database can be reduced.

[0081] (Item 2)

[0082] The sample analysis auxiliary device described in item 2 is, in the sample analysis auxiliary device described in item 1,

[0083] Information used to identify the compound includes any one of the compound name, CAS number, and PubChem ID.

[0084] In the sample analysis auxiliary device described in item 2, the target compound can be identified and entered into the compound list by compound name, CAS number, or PubChem ID. Identifying the structure of the target compound by CAS number or PubChem ID is preferable to using compound name, which is prone to input errors.

[0085] (Item 3)

[0086] The sample analysis auxiliary device described in item 3 is, in the sample analysis auxiliary device described in item 1 or item 2,

[0087] Information used to identify the compound includes information for simultaneously identifying multiple known compounds.

[0088] In the sample analysis auxiliary device described in item 3, multiple known compounds can be identified in batches by inputting information for the simultaneous identification of multiple known compounds, thereby making it easier to input the compound list.

[0089] (Item 4)

[0090] The sample analysis auxiliary device described in item 4 is, in any one of items 1 to 3, the sample analysis auxiliary device.

[0091] The analytical conditions of one or more compounds displayed on the analytical conditions display unit can be edited.

[0092] In the sample analysis auxiliary device described in item 4, for example, the analytical conditions for each analyte compound can be confirmed and the analyte compound can be selected for rejection, or the residence time or cycle time can be changed when the retention times of a large number of compounds overlap in the analysis performed using a chromatograph.

[0093] (Item 5)

[0094] The sample analysis auxiliary device described in item 5 is, in any one of items 1 to 4, the sample analysis auxiliary device.

[0095] The analysis condition display unit displays information for identifying the compound on the screen of the display unit, and if the information for identifying the compound is changed, the information stored in the storage unit is updated to the changed information.

[0096] In the sample analysis auxiliary device described in item 5, information for identifying compounds can be updated in conjunction with the updating of information related to the sample to be analyzed.

[0097] (Item 6)

[0098] The sample analysis auxiliary device described in item 6 is, in any one of items 1 to 5, the sample analysis auxiliary device.

[0099] The compound is an eluent and / or leachate derived from pharmaceutical products.

[0100] In eluent or leachate testing of pharmaceutical products (E&L testing), mass spectra or product ion spectra obtained through non-target analysis are typically compared with spectra in a library. However, sometimes compound databases containing information such as analytical conditions for a large number (e.g., hundreds) of compounds included in a wide variety of pharmaceutical products are used. In such cases, selecting each analyte compound and extracting the analytical conditions for each analyte compound is time-consuming and laborious. The sample analysis aid device described in item 6 is particularly capable of optimizing the analytical conditions for extracting analyte compounds in E&L testing of pharmaceutical products, a process that has traditionally been time-consuming and laborious.

[0101] Explanation of reference numerals in the attached figures

[0102] 1…Gas Chromatography-Mass Spectrometry System

[0103] 10…Gas Chromatography-Mass Spectrometry Analysis Department

[0104] 20…Control / Processing Department

[0105] 21… Storage Department

[0106] 211…Compound Database

[0107] 22…Sample Analysis Auxiliary Program

[0108] 221…Compound list input receiving unit

[0109] 222…Analysis Condition Reading Section

[0110] 223…Analysis Conditions Display Section

[0111] 224…Analysis and Execution Document Production Department

[0112] 225…Analysis and Control Department

[0113] 226…Analysis and Processing Department

[0114] 25… Input Section

[0115] 26… Display Department

[0116] 31…Compound list display bar

[0117] 311…Compound Name Input Field

[0118] 312…CAS Number Input Field

[0119] 313…ID input field

[0120] 314… Corresponding column display bar

[0121] 32…Keyword Input Button

[0122] 33…Search button

[0123] 34…Column Selection Button

[0124] 35…Mass Spectrometry Analysis Mode Selection Button

[0125] 36…OK button

[0126] 38…Keyword input field

[0127] 39…OK button

[0128] 41…Analysis Condition List Display Bar

[0129] 42…OK button.

Claims

1. A sample analysis auxiliary device, comprising: The storage unit stores information corresponding to the analytical conditions for identifying the compound for each of a plurality of known compounds. Display section; The compound list input receiving unit receives an input of a list of information used to identify one or more analyte compounds; The analysis condition reading unit, with reference to the information stored in the storage unit, reads from the storage unit the analysis conditions of the compounds corresponding to each piece of information in the list received by the compound list input receiving unit for identifying one or more analyte compounds. as well as An analysis condition display unit displays the analysis conditions of one or more compounds read by the analysis condition reading unit.

2. The sample analysis auxiliary device according to claim 1, wherein, Information used to identify the compound includes any one of the compound name, CAS number, and PubChem ID.

3. The sample analysis auxiliary device according to claim 1, wherein, Information used to identify the compound includes information for simultaneously identifying multiple known compounds.

4. The sample analysis auxiliary device according to claim 1, wherein, The analytical conditions of one or more compounds displayed on the analytical conditions display unit can be edited.

5. The sample analysis auxiliary device according to claim 1, wherein, The analysis condition display unit displays information for identifying the compound on the screen of the display unit, and if the information for identifying the compound is changed, the information stored in the storage unit is updated to the changed information.

6. The sample analysis auxiliary device according to claim 1, wherein, The compound is an eluent and / or leachate derived from pharmaceutical products.

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