Sample analysis assistance device

Abstract

This sample analysis assistance device (20) comprises: a storage unit (21) that, for each of a plurality of known compounds, stores information in which information identifying the compound is associated with an analysis condition of the compound; a display unit (26); a compound list input reception unit (221) that receives an input of a list of information identifying one or a plurality of compounds-to-be-analyzed; an analysis condition reading unit (222) that reads, from the storage unit with reference to the information stored in the storage unit, the analysis condition of the compound associated with each piece of the information identifying the one or plurality of compounds-to-be-analyzed included 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 plurality of compounds read by the analysis condition reading unit.

Description

Sample analysis support equipment

[0001] The present invention relates to a sample analysis support device.

[0002] Pharmaceutical packaging and containers are used to store, transport, and store pharmaceuticals. Medical devices are also used to administer pharmaceuticals to patients. During these processes, leachables and exudates from the containers containing pharmaceuticals and the medical devices used to administer pharmaceuticals (hereinafter collectively referred to as "pharmaceutical products") may be contaminated into pharmaceuticals, potentially impairing their efficacy or causing health problems. Therefore, testing for leachables and exudates (E&L testing) is recommended for pharmaceutical products. For example, gas chromatograph mass spectrometers (GC-MS) are used for E&L testing of pharmaceutical products (e.g., Non-Patent Document 1). Conventionally, non-target analysis using the scanning method has been commonly used for E&L testing using gas chromatograph mass spectrometers. Recently, a method has come into use in which a database containing a plurality of known compounds and analytical conditions for each compound in a gas chromatograph mass spectrometer is used, a list of the known compounds recorded there is displayed on a screen, and the analytical conditions for each target compound are extracted by selecting the target compound from the list (e.g., Non-Patent Documents 2 and 3).

[0003] "Evaluation of Extractables (E&L) from Medical Devices and Containers", [online], Shimadzu Techno Research Corporation, [Retrieved September 15, 2023], Internet<URL:https: / / www.shimadzu-techno.co.jp / annai / pha / h09.html> 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, 74 90-107Dennis 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

[0004] The purpose of E&L testing for pharmaceutical products is to evaluate the risks posed by impurities contained in the pharmaceutical product itself or compounds that may be introduced from the pharmaceutical product's manufacturing equipment. Guidelines for E&L testing recommend that prior to conducting the test, a list of compounds that may be contained in the pharmaceutical product being tested be compiled, and that compounds that pose a high risk of causing health damage be prioritized for evaluation. In contrast, compound databases contain information on a large number (e.g., hundreds) of compounds contained in a wide variety of pharmaceutical products. Therefore, it was time-consuming to find and select target compounds from a list of numerous compounds displayed on the screen and then extract analytical conditions for each target compound.

[0005] The problem to be solved by the present invention is to reduce the effort required to extract analytical conditions for a target compound from among analytical conditions for a large number of known compounds stored in a database.

[0006] The sample analysis support device of the present invention, which has been made to solve the above-mentioned problems, comprises: a memory unit in which, for each of a plurality of known compounds, information identifying the compound is stored in association with analytical conditions for the compound; a display unit; a compound list input receiving unit that receives input of a list of information identifying one or more target compounds; an analytical condition reading unit that refers to the information stored in the memory unit and reads out from the memory unit analytical conditions for the compounds associated with each piece of information identifying one or more target compounds listed in the list received by the compound list input receiving unit; and an analytical condition display unit that displays the analytical conditions for the one or more compounds read out by the analytical condition reading unit on the display unit.

[0007] In the sample analysis support device according to the present invention, the user simply inputs a list of information identifying one or more target compounds to be analyzed, and the analytical condition reading unit reads out analytical conditions for the compounds corresponding to each of the information identifying one or more target compounds listed in the input list from among analytical conditions for a plurality of known compounds stored in the memory unit, and the analytical condition display unit displays the analytical conditions for each compound on the display unit. This reduces the effort required to extract analytical conditions for target compounds from analytical conditions for a large number of known compounds stored in a database.

[0008] 1 is a diagram showing the configuration of the main parts of a gas chromatograph mass spectrometry system including a sample analysis support device according to the present invention. FIG. 1 is an example of a compound list input screen in this embodiment. FIG. 2 is an example of a keyword input screen in this embodiment. FIG. 3 is an example of an analysis condition list display screen in this embodiment. FIG. 4 is an example of an embodiment in which compounds are grouped by initial setting and a measurement time range is set. FIG. 5 is an example of an embodiment in which a measurement time range is changed by dividing one initially set group into two.

[0009] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS An embodiment of a sample analysis support device according to the present invention will be described below with reference to the drawings.

[0010] 1 shows the main components of a gas chromatograph mass spectrometry system 1 including a sample analysis support device according to this embodiment. The gas chromatograph mass spectrometry system 1 according to this embodiment is used to perform E&L testing for extractables and leachables from, for example, containers containing pharmaceuticals and medical devices used to administer pharmaceuticals (hereinafter collectively referred to as "medical supplies"). These medical supplies include primary materials such as packaging that come into direct contact with pharmaceuticals, and secondary materials such as cardboard that come into indirect contact with pharmaceuticals.

[0011] The gas chromatograph mass spectrometry system 1 comprises a gas chromatograph mass spectrometry unit (GC-MS) 10, which is a measurement unit, and a control and processing unit 20. The control and processing unit 20 corresponds to the sample analysis support device according to the present invention.

[0012] The gas chromatograph mass analyzer 10 combines a gas chromatograph for separating various compounds contained in a sample with a mass analyzer for sequentially analyzing the compounds separated by the gas chromatograph. The mass analyzer of this embodiment uses a mass analyzer (such as a triple quadrupole mass analyzer or an ion trap-time-of-flight mass analyzer) configured to be able to perform MS and MS / MS measurements. In this embodiment, such a configuration is used to enable MRM and product ion scan measurements in addition to SIM and scan measurements. However, if only SIM and / or scan measurements are to be performed, a single quadrupole mass analyzer or the like may also be used.

[0013] 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 stores information on a large number (e.g., several hundred) of known compounds that may be contained in various medical supplies. This information includes, in addition to an identification number (ID) in the database, for example, compound-specific information, information on measurement conditions, information on analysis conditions, and supplemental information. In this specification, the compound measurement conditions and analysis conditions are collectively referred to as analysis conditions.

[0014] The compound-specific information may include, for example, the compound name, CAS number, PubChem ID, chemical formula, and structural formula. The information on the measurement conditions of the compound may include, for example, the type and temperature of a column that can be used to measure the compound in a gas chromatograph, the type and flow rate of the carrier gas, the retention index and retention time for each column, and information on the mass analysis mode (SIM measurement, scan measurement, MRM measurement, product ion scan measurement, etc.) and the mass-to-charge ratio of ions (the mass-to-charge ratio of the monitor ion during SIM measurement, the mass-to-charge ratio range during scan measurement, the mass-to-charge ratio of the MRM transition (precursor ion and product ion) during MRM measurement, and the mass-to-charge ratio range of the precursor ion and product ion during MS / MS measurement). The information on the analysis conditions of the compound may include, for example, information on the mass spectrum, product ion spectrum, reference value of the intensity ratio of the quantitation ion to the confirmation ion, reference value of the intensity ratio of the quantitation MRM transition to the confirmation MRM transition, calibration curve, lower limit of quantitation, and lower limit of detection. The supplemental information includes keywords related to each compound, such as the type of product (e.g., syringe, injector, packaging paper) that may contain each compound, and information about the manufacturing equipment, manufacturing plant, and manufacturer into which the compound may be mixed during the manufacturing process.

[0015] The control / processing unit 20 includes, as functional blocks, a compound list input receiving unit 221, an analysis condition reading unit 222, an analysis condition display unit 223, an analysis execution file creation unit 224, an analysis control unit 225, and an analysis processing unit 226. The control / processing unit 20 is actually a personal computer, and each of the above functional blocks is realized by executing pre-installed software (sample analysis support program 22) on a processor. In addition, an input unit 25 and a display unit 26 are connected to the control / processing unit 20. The sample analysis support program 22 can be executed in a general user mode in which logging in is performed without an ID or password, and in an administrator mode in which logging in is performed using an ID and password that grants predetermined authority.

[0016] Next, the procedure for E&L testing of medical supplies using the gas chromatograph mass spectrometry system of this embodiment will be described.

[0017] When the user instructs execution of an analysis, the compound list input receiving unit 221 displays a screen that prompts the user to input a list of compounds to be analyzed on the display unit 26. This screen may be in the form of a table that has, for example, a field for inputting the compound name, CAS number, or PubChem ID, and a field for displaying the type of column that can measure the compound corresponding to the input compound name, CAS number, or PubChem ID.

[0018] 2 shows an example of a screen for inputting a list of target compounds for analysis. This screen displays a compound list display field 31, a keyword input button 32, a search button 33, a column selection button 34, a mass analysis mode selection button 35, and a decision button 36. The compound list display field 31 includes a compound name input field 311, a CAS number input field 312, a PubChem ID input field 313, and a corresponding column display field 314.

[0019] When the user enters a compound name, CAS number, or PubChem ID for each target compound in either the compound name input field 311, the CAS number input field 312, or the PubChem ID input field 313 and presses the search button 33, the compound list input accepting unit 221 checks the compound's unique information stored in the compound database 211 to determine whether data with the input compound name, CAS number, or PubChem ID exists. If data with the input compound name, CAS number, or PubChem ID exists in the compound database 211, the unit further identifies the type of column that can be used to measure the compound based on the compound's measurement 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 target compound entered, the compound list input accepting unit 221 displays a circle in the display field for each column if the column is usable. The number of compounds to be displayed in the compound list display field 31 can be changed as appropriate by a predetermined operation via the input unit 25. Alternatively, a line may be automatically added each time the user inputs a compound name, a CAS number, or a PubChem ID into the compound name input field 311, the CAS number input field 312, or the PubChem ID input field 313.

[0020] Here, an example has been described in which the user directly inputs a compound name, a CAS number, or a PubChem ID into any of the compound name input field 311, the CAS number input field 312, and the PubChem ID input field 313. However, if a compound list containing compound names, CAS numbers, or PubChem IDs has been created in advance and stored in the storage unit 21 or the like, the compound name, etc. can be input by reading out 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, thereby reading out the compound list contained in that file.

[0021] 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 user on the screen of the display unit 26 that a compound corresponding to the information entered by the user is not stored in the compound database 211. Then, the user is asked whether or not to add the compound to the compound database 211.

[0022] When the user instructs addition to the compound database 211, another pop-up window is displayed, for example, to prompt the user to input information (compound specific information, analysis conditions, and supplementary information) required for registration in the compound database 211. When the user inputs the required items, a new identification number (ID) is assigned and the compound is registered in the compound database 211.

[0023] The user can also enter keywords along with the compounds to be analyzed, either individually or as a list. For example, if a user enters compounds to perform E&L testing on drug a manufactured by A Pharmaceuticals, and also enters keywords such as "A Pharmaceuticals" and "drug a," information such as "A Pharmaceuticals" and "drug a" is added to the compound database 211 as supplemental information for each compound entered by the user. By adding supplemental information in this way, when performing E&L testing on the same pharmaceutical product that was previously subjected to E&L testing, multiple compounds can be entered at once by simply entering keywords, as described below.

[0024] A user can create a list of compounds by entering not only information identifying a single compound, such as a compound name, CAS number, or PubChem ID, but also information identifying multiple compounds simultaneously. In the example shown in FIG. 2 , when the user presses the keyword input button 32, a keyword input screen such as that shown in FIG. 3 is displayed. This screen initially displays only one keyword input field 38 and a confirm button 39. When the user enters a keyword in the first keyword input field 38, the next keyword input field 38 is automatically added below it. Thus, the user can enter any number of keywords. When the user enters a keyword in the keyword input field 38 and presses the confirm button 39, the compound list input accepting unit 221 compares the keyword with the supplemental information for the compound stored in the compound database 211. Compounds for which all of the entered keywords are registered as supplemental information are simultaneously retrieved from the compound database 211, and the same information as above is entered 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 is performed that includes all of the input keywords, but it is also possible to perform a so-called OR search and read out all compounds that include any of the input keywords from the compound database 211 at once.

[0025] The user checks the display in the corresponding column display field 314 and operates the column selection button 34 to select one of the columns that can be used for all of the target compounds. The column selection button 34 is in a pull-down format, and only columns that can be used for all of the target compounds can be selected. In the example shown in FIG. 2 , column A or column B can be selected by pulling down the column selection button 34. Next, the user operates the mass analysis mode selection button 35 to select the mass analysis mode for measuring each target compound. The mass analysis mode selection button 35 is also in a pull-down format, and allows selection of scan measurement, SIM measurement, product ion scan measurement, or MRM measurement.

[0026] When the user selects a column type and a mass analysis mode and presses the decision button 36, the compound list input receiving unit 221 determines the compound currently displayed in the compound list display field 31 as the provisional target compound for analysis. If multiple types of columns and / or mass analysis modes are to be used for the target compound, the user need only create a compound list of target compounds for analysis that have the same combination of column type and mass analysis mode and press the decision button 36, and repeat this operation for each combination of column type and mass analysis mode.

[0027] Next, the analysis condition reading unit 222 reads from the compound database 211 the measurement conditions, etc., related to the type of column selected by the user using the column selection button 34 and the mass analysis mode selected using the mass analysis mode selection button 35 for each of the target compounds to be analyzed determined by the compound list input receiving unit 221.

[0028] When the analytical condition reading section 222 reads out the measurement conditions for each compound to be analyzed, the analytical condition display section 223 displays the read information in a table format on the display section 26 .

[0029] 4 shows an example of a display of a list of analytical conditions. This screen displays an analytical condition list display field 41 and a decision button 42. The analytical condition list display field 41 displays the serial number, type, measurement mode, lower limit of quantitation, method number, compound name, retention index, retention time, and CAS number for each of the target compounds to be analyzed determined by the compound list input receiving unit 221. Filter buttons are provided in these item fields, and these buttons can be used to sort the list or narrow down the items to be displayed. The items displayed in the analytical condition list display field 41 can be changed as appropriate by an administrator who runs the sample analysis support program using, for example, an ID and password with administrator privileges.

[0030] The serial number column displays the identification number (ID) of the compound in the compound database 211. The type column displays whether the user has selected the compound as the final target compound for analysis (Target). When the analytical condition display unit 223 first displays a list of analytical conditions, the analytical conditions for the provisional target compound for analysis are displayed, and "Target" is displayed in the type column for all compounds.

[0031] The measurement mode field displays the mass analysis mode selected by the user by operating the mass analysis mode selection button 35 on the screen shown in FIG. 2. The quantitation lower limit field displays the quantitation lower limit of the compound stored in the compound database 211. The method number field displays the analyte compounds to be measured at one time with the same number. In the example of FIG. 4, all are displayed as "1," and the measurement conditions for these analyte compounds are written to one method file (analysis execution file) and measured at one time. The retention index field and retention time field display the retention index and retention time of the compound stored in the compound database 211. Although not included in the display example of FIG. 4, a supplementary information field may be displayed in the analysis condition list display field 41. In this case, the supplementary information field displays supplementary information for the compound stored in the compound database 211.

[0032] The screen shown in Fig. 4 allows the user to confirm the specific measurement conditions and lower limit of quantification of the compound that the user selected as the target compound on the screen shown in Fig. 2. For example, if the user determines that the displayed measurement conditions or lower limit of quantification are inappropriate, the user can exclude the compound from the target compounds by switching the display in the type column from "Target" to blank. The excluded compound can then be analyzed, for example, by a different measurement method.

[0033] The display example in Figure 4 shows the state in which two compounds, Morpholine and 3-Methyl-2(5H)-furanone, have been excluded from the list of target compounds that the user selected as target compounds for analysis on the display screen shown in Figure 2. Even if a compound has been excluded from the list of target compounds for analysis, if the user selects "Target" by clicking on the type field for that compound, that compound can be selected again as a target compound for analysis.

[0034] The compounds determined as tentative target compounds for analysis may include compounds for which the measurement conditions for the mass analysis mode selected by the user on the screen of Fig. 2 are not recorded in the compound database 211. In such cases, in the list of analysis conditions shown in Fig. 4, the row for the compound for which the measurement conditions for the analysis mode selected by the user are not recorded is highlighted (colored, blinking, etc.) to prompt the user to change the mass analysis mode (change the setting in the measurement mode field) or exclude the compound from the target compounds for analysis (exclude it from "Target" in the type field).

[0035] Furthermore, when a user executes the sample analysis support program 22 using an ID and password with administrator privileges, the user can edit (add, change, or delete) any item displayed in the analysis condition list shown in FIG. 4 , except for the unchanging information of compound name, CAS number, and PubChem ID. For example, the user can change the measurement conditions read from the compound database 211. Alternatively, the user can add supplemental information common to multiple compounds on this screen. This allows the user to use the added supplemental information as a keyword the next time a list of target compounds is created, thereby allowing the user to enter all compounds included in the currently entered compound list at once. Furthermore, the user can update information such as product type and manufacturing equipment included in the supplemental information as needed to keep up with updates to the pharmaceutical products being handled.

[0036] In the list of analytical conditions shown in FIG. 4 , when multiple compounds with similar retention times are selected, the time interval (loop time) between mass analysis runs for each compound may be too long if the dwell time (the length of time required to perform a single mass analysis of each compound) is left at its default value. For example, in SIM or MRM measurements, after the measurement is completed, the peak shape of the mass chromatogram is determined from the intensity values ​​of multiple measurements performed at each compound's retention time, and the compound is quantified from the area (or height) of the peak. In this case, if the loop time is too long, the number of measurement points may be insufficient, resulting in an inaccurate peak shape and reduced accuracy of the quantification value. To address this issue, the loop time is fixed at a constant value in this embodiment. This loop time is preset to a length that allows the peaks of each compound in the chromatogram to be constructed with at least the required number of measurement points (e.g., 10 points) (in other words, a length equal to or less than the time required to measure each compound separated in a gas chromatograph column divided by the required number of measurement points (e.g., 10 points)). When the user sets the required processing time (including using the initial required processing time as is), the measurement time for each compound is set accordingly, and the dwell time is also determined. The required processing time refers to the minimum value (minimum measurement time) of the length of measurement time centered on the retention time (or retention index) of each compound. The required processing time is set to, for example, 0.3 min, and in this case, the measurement time range for each compound is set so that each compound is measured within a time period of at least ±0.3 min centered on the retention time.

[0037] In this embodiment, when the analytical condition list shown in FIG. 4 is displayed or when a user with administrator privileges changes the measurement conditions, a screen such as that shown in FIG. 5 is displayed on the display unit 26. The screen shown in FIG. 5 lists the measurement times for each compound vertically, with the horizontal axis representing the measurement time. In the initial setting, as shown in FIG. 5, one or more compounds whose set measurement times, determined based on the required processing time set by the user, overlap in time. The dwell time is calculated by dividing the fixed loop time for each group by the number of measurement ions (measurement ions in the case of SIM analysis, measurement MRM transitions in the case of MRM analysis; hereafter, both will be referred to as measurement ions) used in the analysis of the compounds included in that group. In this example, compounds A to C are grouped together (Group 1), and compounds D to H are grouped together (Group 2). In each group, an actual measurement time range is set to cover the set measurement times for all compounds, and each compound is measured sequentially within that actual measurement time range.

[0038] When the number of compounds in each group is small, the above initial setting allocates sufficient dwell time to each compound, but when the number of measurement ions used in the analysis of the compounds in one group increases, it may not be possible to allocate sufficient dwell time to each measurement ion for the compounds in that group. Therefore, if the dwell time allocated to each measurement ion falls below a predetermined time, it is recommended to highlight the group (shown by a thick dashed line in Figure 5) and prompt the user to confirm.

[0039] The user checks the dwell time assigned to each measurement ion of each compound included in the highlighted group, and if they determine that the dwell time is insufficient, they input a command to split the group. When the user instructs group splitting, the specified group is split into two. In this case, the set measurement time for at least one compound will straddle the boundary between the two groups. Measurement ions for compounds whose set measurement time straddles the boundary between the two groups are measured across the two groups. The example shown in Figure 6 shows the split of Group 2 in Figure 5, with compounds D to K divided into Group 2-1, which includes compounds D to H, and Group 2-2, which includes compounds H to K. Compound H, whose set measurement time straddles the boundary between the two groups, is measured across the two groups. This allows sufficient dwell time to be assigned to each measurement ion even when there are a large number of compounds with similar retention times and a large number of measurement ions for those compounds. Furthermore, the loop time can be maintained constant even when a single compound is measured across multiple groups.

[0040] When the user presses the decision button 42 on the screen shown in FIG. 4 , the compound currently displayed as "Target" in the type column is set as the final target compound for analysis. The analysis execution file creation unit 224 creates an analysis execution file describing the measurement conditions for executing the mass analysis mode selected in the measurement mode column for each of the finally determined target compounds for analysis. Furthermore, if the user makes any changes to the information read from the compound database 211, the user is asked whether or not to reflect the changes as information in the compound database 211. When the user instructs to reflect the information, the changed content is saved in the compound database 211.

[0041] After creating the analysis execution file, the user sets the sample to be analyzed and instructs the start of measurement by performing a predetermined operation through the input unit 25.The analysis control unit 225 then measures each compound to be analyzed under the measurement conditions described in the analysis execution file.

[0042] Each compound in a sample introduced into the gas chromatograph mass spectrometer 10 is separated in a gas chromatograph column, and flows out of the column at the retention time of each compound and is subjected to mass analysis. The mass spectrometer repeatedly performs scan measurements within a predetermined time period centered on the retention time (or retention index) of each target compound. Data acquired during measurement is sequentially stored in the memory unit 21.

[0043] After the measurement is completed, the analysis processing unit 226 reads out the measurement data stored in the storage unit 21 and performs an analysis process. In this example, since each target compound is scanned and a mass spectrum is obtained, the analysis processing unit 226 reads out the mass spectrum of each target compound from the compound database 211 and determines the degree of match with the mass spectrum obtained by the measurement (for example, the degree of match in the mass-to-charge ratio and normalized intensity of the mass peak). If the degree of match exceeds a predetermined threshold, it is determined that the sample contains the target compound. Furthermore, the intensity of the mass peak of the target ion appearing in the mass spectrum is compared with a calibration curve to quantify the target compound.

[0044] While the case of performing a scan measurement has been described above, when performing a SIM measurement, the analysis processor 226 reads from the compound database 211 a reference value for the intensity ratio between the quantitation ion and the confirmation ion, and determines whether the sample contains a target compound based on whether the difference between the intensity ratio between the quantitation ion and the confirmation ion obtained by the measurement and the reference value is within a predetermined range. If the target compound is contained, the analysis processor 226 further quantifies the target compound by comparing the measured intensity of the quantitation ion with a calibration curve. When performing a product ion scan measurement, the analysis processor 226 reads from the compound database 211 the product ion spectrum of each target compound and determines the degree of match with the product ion spectrum obtained by the measurement (e.g., the degree of match between the mass-to-charge ratio and normalized intensity of the mass peak). If the degree of match exceeds a predetermined threshold, the analysis processor 226 determines that the target compound is contained in the sample. Furthermore, the analysis processor 226 quantifies the target compound by comparing the intensity of the mass peak of the target ion (product ion) appearing in the product ion spectrum with a calibration curve.

[0045] Non-targeted analysis is a common method for E&L testing of pharmaceutical products. In non-targeted analysis, a scan measurement is performed without specifying the target compound in advance, and a mass spectrum is acquired. The mass spectrum acquired from the measurement is then compared with the mass spectra of known compounds stored in a library, and candidate compounds are listed in order of highest match.

[0046] However, because the library contains the mass spectra of many known compounds, a large number of compounds with similar degrees of match are listed, making it difficult to determine which of them actually contain the sample.

[0047] In E&L testing of pharmaceutical products, it is particularly desirable to analyze in detail impurities contained in the pharmaceutical product itself or compounds that may be mixed in from the pharmaceutical product manufacturing equipment and that pose a high risk of health damage due to leaching into pharmaceutical products. In other words, it is advisable to perform E&L testing for these compounds using a measurement method with higher selectivity.

[0048] Therefore, targeted analysis is effective in that it involves pre-specifying compounds that may be present in pharmaceutical products and pose a high risk of health hazards due to leaching into pharmaceutical products. In targeted analysis, the target compound is selected in advance from a large number of known compounds stored in a compound database. The mass spectrum and product ion spectrum acquired by measurement are compared with the mass spectrum and product ion spectrum of the known compound stored in the compound database to determine the degree of match. Therefore, unlike conventional E&L testing using libraries, a large number of candidate compounds with similar degrees of match are not listed, making it easy to determine whether or not the target compound is present in the sample. Targeted analysis may also involve SIM or MRM measurements, which have higher compound selectivity than scan or product ion scan measurements, to determine whether or not the target compound is present and, if so, its content.

[0049] However, since compound databases contain information on a large number (e.g., hundreds) of compounds contained in a wide variety of pharmaceutical products, it was time-consuming to find and select target compounds from a list of many compounds displayed on the screen and then extract analytical conditions for the target compounds.

[0050] In contrast, in the gas chromatograph mass spectrometry system 1 of this embodiment, the user simply inputs a list of information specifying one or more target compounds on a screen such as that shown in Fig. 2, and the analytical condition reading unit 222 reads out analytical conditions for the compounds corresponding to each of the information specifying one or more target compounds listed in the input list from among analytical conditions for a plurality of known compounds stored in the compound database 211, and the analytical condition display unit 223 displays the analytical conditions for each compound on the display unit 26. This reduces the effort required to extract analytical conditions for target compounds from among analytical conditions for the many known compounds stored in the compound database 211.

[0051] The above embodiment is merely an example and can be modified as appropriate in accordance with the spirit of the present invention.

[0052] Although the above embodiment is a gas chromatograph mass spectrometry system 1, a similar configuration can also be employed in analytical systems equipped with other analytical devices. Furthermore, while the above embodiment is configured for the purpose of E&L testing of pharmaceutical products, a similar configuration can also be used for other analyses. For example, in the above embodiment, supplemental information for compounds stored in the compound database 211 is exemplified as information related to E&L testing of pharmaceutical products, but any information can be registered as supplemental information, and it is preferable to register appropriate information depending on the characteristics of the analyte, the purpose of the analysis, the analysis method, etc.

[0053] The display screens in the above embodiments are merely examples, and the display format can be changed as appropriate.

[0054] Aspects It will be apparent to those skilled in the art that the exemplary embodiments described above are examples of the following aspects.

[0055] (Item 1) A sample analysis support device according to one embodiment of the present invention comprises: a memory unit storing, for each of a plurality of known compounds, information identifying the compound and its analytical conditions; a display unit; a compound list input receiving unit that receives input of a list of information identifying one or more target compounds; an analytical condition reading unit that refers to the information stored in the memory unit and reads out from the memory unit analytical conditions for the compounds associated with each piece of information identifying one or more target compounds listed in the list received by the compound list input receiving unit; and an analytical condition display unit that displays on the display unit the analytical conditions for the one or more compounds read out by the analytical condition reading unit.

[0056] In the sample analysis support device according to paragraph 1, the user simply inputs a list of information identifying one or more target compounds, and the analytical condition display unit reads out analytical conditions for the compound corresponding to each of the information identifying one or more target compounds listed in the input list from the analytical conditions for multiple known compounds stored in the memory unit, and the analytical condition display unit displays the analytical conditions for each compound on the display unit. This reduces the effort required to extract analytical conditions for target compounds from the analytical conditions for the many known compounds stored in the database.

[0057] (Clause 2) The sample analysis support device according to clause 2 is the sample analysis support device according to clause 1, wherein the information identifying the compound includes any one of a compound name, a CAS number, and a PubChem ID.

[0058] In the sample analysis support device according to paragraph 2, a compound list can be input by specifying the target compound by compound name, CAS number, or PubChem ID. It is more preferable to specify the target compound by CAS number or PubChem ID rather than by compound name, which is prone to input errors.

[0059] (Clause 3) The sample analysis support device according to clause 3 is the sample analysis support device according to clause 1 or 2, wherein the information identifying the compound includes information identifying a plurality of known compounds simultaneously.

[0060] In the sample analysis support device according to the third aspect, by inputting information that simultaneously identifies a plurality of known compounds, the plurality of known compounds can be identified at once, making it possible to input a compound list more easily.

[0061] (4) The sample analysis support device according to 4 is the sample analysis support device according to any one of 1 to 3, wherein the analysis conditions for the one or more compounds displayed on the display unit can be edited by the analysis condition display unit.

[0062] The sample analysis support device according to paragraph 4 can, for example, check the analysis conditions for each target compound to select the target compounds, or change the dwell time or loop time when the retention times of multiple compounds overlap during analysis using a chromatograph.

[0063] (Clause 5) The sample analysis support device according to clause 5 is the sample analysis support device according to any one of clauses 1 to 4, wherein the analysis condition display unit displays information identifying the compound on a screen displayed on the display unit, and when a change is made to the information identifying the compound, the information stored in the memory unit is updated to the changed information.

[0064] In the sample analysis support device according to the fifth aspect, the information specifying the compound can be updated in accordance with updates to the information related to the sample to be analyzed.

[0065] (Item 6) The sample analysis support device according to item 6 is the sample analysis support device according to any one of items 1 to 5, wherein the compound is an eluate and / or exudate from a medical product.

[0066] In tests for extractables and leachables (E&L tests) of pharmaceutical products, it is common to compare mass spectra and product ion spectra obtained through non-target analysis with those stored in a library. However, compound databases containing information on analytical conditions for a large number (e.g., hundreds) of compounds contained in a wide variety of pharmaceutical products may also be used. In such cases, selecting target compounds one by one and extracting analytical conditions for each target compound is a time-consuming process. The sample analysis support device according to paragraph 6 is particularly suitable for extracting analytical conditions for target compounds in E&L tests of pharmaceutical products, which has traditionally been a time-consuming process.

[0067] DESCRIPTION OF SYMBOLS 1...Gas chromatograph mass spectrometry system 10...Gas chromatograph mass spectrometry section 20...Control and processing section 21...Memory section 211...Compound database 22...Sample analysis support program 221...Compound list input acceptance section 222...Analysis condition reading section 223...Analysis condition display section 224...Analysis execution file creation section 225...Analysis control section 226...Analysis processing section 25...Input section 26...Display section 31...Compound list display field 311...Compound name input field 312...CAS number input field 313...ID input field 314...Corresponding column display field 32...Keyword input button 33...Search button 34...Column selection button 35...Mass analysis mode selection button 36...Decision button 38...Keyword input field 39...Decision button 41...Analysis condition list display field 42...Decision button

Claims

1. A storage unit that stores information relating to the identification of a compound and the analytical conditions for that compound for each of several known compounds, Display unit and A compound list input receiving unit that accepts input of a list of information identifying one or more target compounds for analysis, An analysis condition reading unit reads from the storage unit the analysis conditions for compounds associated with each piece of information identifying one or more target compounds listed in the list received by the compound list input receiving unit, by referring to the information stored in the storage unit. An analysis condition display unit that displays the analysis conditions of one or more compounds read out by the analysis condition reading unit on the display unit. A sample analysis support device equipped with the following features.

2. The sample analysis support device according to claim 1, wherein the information identifying the compound includes any of the following: a compound name, a CAS number, and a PubChem ID.

3. The sample analysis support apparatus according to claim 1, wherein the information for identifying the compound includes information for simultaneously identifying multiple known compounds.

4. The sample analysis support device according to claim 1, wherein the analysis condition display unit allows editing of the analysis conditions of the one or more compounds displayed on the display unit.

5. The memory unit further stores supplemental information relating to the plurality of known compounds, The sample analysis support apparatus according to claim 1, wherein the analysis condition display unit further displays supplementary information of the compound read out by the analysis condition reading unit, and updates the information stored in the storage unit with the changed information when a change is made to the analysis condition or supplementary information displayed on the display unit.

6. The sample analysis support device according to claim 1, wherein the compound is an eluate and / or leachate from a pharmaceutical product.

7. The sample analysis support apparatus according to claim 1, wherein the analysis condition display unit further displays information identifying the one or more target compounds on the display unit.