Liquid chromatograph management system and management method

Abstract

This simplifies the calculation of the formulas used for scaling up. [Solution] One aspect of the present invention is a system for acquiring information used when determining analytical conditions for operating an LC apparatus, comprising: a first storage unit (321) that stores a first analytical result file containing a first analytical result obtained by performing LC analysis on a predetermined sample containing one or more compounds under first analytical conditions; a second storage unit (322) that stores a second preparative result file containing a second analytical result obtained by performing LC analysis on a predetermined sample containing one or more compounds under second analytical conditions in which the mobile phase flow rate or sample injection volume is larger than that of the first analytical conditions; a search unit (312) that searches for a second analytical result associated with the same compound as the compound associated with the first analytical result; an association information creation unit (311) that creates association information for each compound based on the search results, associating the first analytical result with the second analytical result; and a display processing unit (315) that displays the association information.

Description

[Technical Field]

[0001] The present invention relates to a system and method for managing a liquid chromatograph apparatus, and in particular, to a system and method for managing a preparative liquid chromatograph apparatus that fractions components in a sample. [Background Art]

[0002] In fields such as the research, development, and manufacturing of pharmaceutical products, preparative liquid chromatography (hereinafter, "liquid chromatography" may be referred to as "LC") is widely used to fractionate and purify target components from samples containing chemically synthesized components (compounds). To accurately and efficiently fractionate a target compound in a sample using preparative LC, it is important to appropriately set fractionation conditions such as the column type, mobile phase type, mobile phase flow rate, and gradient conditions (temporal changes in mobile phase concentration) in accordance with the target compound.

[0003] When searching for fractionation conditions for preparative LC, a method called scale-up is sometimes used, in which optimal analytical conditions are obtained via LC analysis using a column with a smaller capacity than a preparative column (a standard analytical column), that is, "analytical scale" LC analysis, and these analytical conditions are adjusted to suit LC analysis using a large-capacity preparative column, that is, "preparative scale" LC analysis. Determination of fractionation conditions via such scale-up is generally performed by a person with sufficient knowledge and experience regarding LC, but even so, the work is quite cumbersome, time-consuming, and labor-intensive. In contrast, systems (software) that enable even a person in charge (user) with little knowledge of LC to determine appropriate fractionation conditions have been conventionally provided (see Non-Patent Document 1). [Prior Art Documents] [Patent Documents]

[0004] [Patent Document 1] International Publication No. WO 2016 / 021715 [Non-Patent Documents]

[0005] [Non-Patent Document 1] "ASAPrep Automatic Scale-Up System for Reverse Phase Purification," [Online], [Accessed February 21, 2025], Shimadzu Corporation, Internet <URL: https: / / www.an.shimadzu.co.jp / products / liquid-chromatography / preparative-hplc / asaprep / index.html> [Overview of the project] [Problems that the invention aims to solve]

[0006] The "ASAPrep optimized purification" included in the system described in Non-Patent Document 1 allows for the calculation of the initial concentration of the organic mobile phase under preparative conditions that yield the desired results on a preparative scale, based on retention time information of the target compound obtained by performing LC analysis on an analytical scale using calculation formulas pre-registered in the software. Then, it is possible to determine the gradient conditions based on this calculated initial concentration of the organic mobile phase. To obtain the calculation formula showing the relationship between retention time and the initial concentration of the organic mobile phase in LC analysis, for example, the method described in Patent Document 1 can be used.

[0007] According to Patent Document 1, a formula for scaling up from an analytical scale to a preparative scale can be determined based on LC analysis data obtained by performing analytical-scale LC analysis on a standard sample containing the target compound, and LC preparative data obtained by performing preparative-scale LC analysis on the same standard sample at a different analytical scale (usually with different column capacities, etc.). In other words, determining this formula requires a considerable amount of data obtained by performing LC analysis on multiple compounds under different conditions. Furthermore, since this formula depends on the type of column used, if you want to perform preparative analysis using a different type of column than the one corresponding to an already registered formula, you need to create a new formula based on the LC analysis results at a preparative scale using the column you are using. This work is usually performed by engineers from the equipment manufacturer or, in some cases, by administrators with specialized knowledge on the equipment user's side, but the work is quite complicated, has problems such as poor workability, being time-consuming, or being prone to errors.

[0008] This invention has been made in view of these problems, and its main objective is to provide an LC management system and management method that simplifies the process of acquiring calculation formulas and equivalent information used to determine appropriate preparation conditions through scaling up, thereby improving work efficiency and reducing work errors. [Means for solving the problem]

[0009] One aspect of the liquid chromatograph management system according to the present invention, which was developed to solve the above problems, is a management system for acquiring information used when determining analytical conditions for operating a liquid chromatograph apparatus, A first storage unit that stores one or more first analysis result files containing first analysis results obtained by liquid chromatographic analysis of a predetermined sample containing one or more compounds under first analysis conditions, A second storage unit that stores multiple second analysis result files, including a second analysis result obtained by performing liquid chromatography analysis on a predetermined sample containing one or more compounds under second analysis conditions where the mobile phase flow rate or sample injection volume is greater than that of the first analysis conditions; A search unit searches for a second analysis result in the second analysis result file stored in the second storage unit that corresponds to the same compound as the first analysis result in the first analysis result file stored in the first storage unit, Based on the search results by the search unit, the association information creation unit creates association information for each compound, which associates the first analysis result with the second analysis result or associates the first analysis result file with the second analysis result file. A display processing unit that displays the aforementioned association information on a screen, It is equipped with the following features.

[0010] Furthermore, one aspect of the liquid chromatograph management method according to the present invention, which was developed to solve the above problems, is a management method that uses a computer to acquire information used when determining analytical conditions for operating a liquid chromatograph apparatus, wherein the computer is A first step of storing one or more first analysis result files containing first analysis results obtained by liquid chromatographic analysis of a predetermined sample containing one or more compounds under first analytical conditions, A second step of storing multiple second analysis result files, each containing a second analysis result obtained by performing liquid chromatography analysis on a predetermined sample containing one or more compounds under second analysis conditions where the mobile phase flow rate or sample injection volume is greater than that of the first analysis conditions. A third step of searching the second analysis result file for a second analysis result that corresponds to the same compound as the first analysis result in the first analysis result file. A fourth step is to create association information for each compound based on the results of the search, which associates the first analysis result with the second analysis result or associates the first analysis result file with the second analysis result file, and The fifth step is to display the aforementioned association information on the display screen. This is what it does. [Effects of the Invention]

[0011] In one embodiment of the liquid chromatograph management system and management method according to the present invention, the process of searching for and displaying a first analysis result and a second analysis result for the same compound obtained under different analytical conditions is automated, eliminating the need for the operator to perform these tasks themselves. Furthermore, the operator can easily compare the first analysis result and the second analysis result for the same compound based on the correlation information displayed on the display screen. As a result, according to the present invention, the work of the operator when obtaining calculation formulas and equivalent information used to determine appropriate preparative conditions through scale-up can be simplified, improving work efficiency and reducing work errors, thereby enabling the setting of more appropriate preparative conditions. [Brief explanation of the drawing]

[0012] [Figure 1] A schematic block diagram showing an example of a sorting condition determination system including one embodiment of the LC management system according to the present invention. [Figure 2] A schematic block diagram showing an example of a preparative LC device using preparative conditions determined by the LC management system according to the present invention. [Figure 3] A functional block diagram of the portioning and management unit in Figure 1. [Figure 4] A flowchart showing an example of the operation procedure and processing procedure for determining the calculation formula for determining the sorting conditions in the LC management system of this embodiment. [Figure 5] A diagram showing an example of the analysis data selection screen. [Figure 6]FIG. 1 is a diagram showing an example of a fractionation condition calculation screen showing a state where analysis data is selected. [Figure 7] FIG. 2 is a diagram showing an example of a compound table after fractionation data is searched on the fractionation condition calculation screen. [Figure 8] FIG. 3 is a diagram showing a part (right part) of the fractionation condition calculation screen after calculation of an arithmetic expression is performed. [Figure 9] FIG. 4 is a diagram showing another example of a compound table after fractionation data is searched on the fractionation condition calculation screen (when three or more pieces of fractionation data exist for one compound). [Figure 10] FIG. 5 is a diagram showing an example of a context menu. [Figure 11] FIG. 6 is a diagram showing an example of display on a compound table when a fractionation retention time is changed on the compound table. [Figure 12] FIG. 7 is a diagram showing an example of a fractionation data selection screen displayed when changing a fractionation data file. [Figure 13] FIG. 8 is a diagram showing an example of a table fractionation condition calculation screen including a compound table when two compound groups, a standard compound group and a hydrophobic compound group, are set. [Figure 14] FIG. 9 is a diagram showing a display area on the right side of the compound table shown in FIG. 13. [Figure 15] FIG. 10 is a diagram showing an example of a graph showing gradient conditions during execution of preparative LC and an arithmetic expression used for determination of the gradient conditions. DETAILED DESCRIPTION OF THE INVENTION

[0013] Hereinafter, one embodiment of an LC management system and an LC management method according to the present invention will be described in detail with reference to the accompanying drawings. The LC management system and the LC management method according to the present invention are typically used to determine fractionation conditions used when fractionating and purifying a specific target compound in a preparative LC apparatus. First, an example of the configuration of a preparative LC apparatus and an example of a fractionation and purification operation using fractionation conditions in the preparative LC apparatus will be schematically described with reference to FIG. 2.

[0014] [Configuration and Operation of Preparative LC Device] Figure 2 is a block diagram of an example of a preparative LC apparatus. This preparative LC apparatus includes an analysis / preparation unit 1A and a control / processing unit 2A. The analysis / preparation unit 1A includes first and second mobile phase containers 10a, 10b, first and second liquid delivery pumps 11a, 11b, a mixer 12, an injector 13, a preparative column 142, a splitter 15, a first detector 16, a fraction collector 17, and a second detector 18.

[0015] The first liquid delivery pump 11a draws in and delivers the first mobile phase, which is an aqueous mobile phase such as water or buffer solution, prepared in the first mobile phase container 10a. The second liquid delivery pump 11b draws in and delivers the second mobile phase, which is an organic mobile phase such as acetonitrile, prepared in the second mobile phase container 10b. The first and second mobile phases are mixed in the mixer 12 and supplied to the preparative column 142 via the injector 13. Both the first and second liquid delivery pumps 11a and 11b operate under the control of the control / processing unit 2A so that their flow rates change over time, thereby enabling high-pressure gradient delivery in which the component ratio of the first and second mobile phases changes over time. However, it is also possible to use a single mobile phase without gradient delivery, or to use mobile phases in which the mixing ratio of the two mobile phases remains constant over time.

[0016] As the preparative column 142, a column with a larger inner diameter than a typical analytical column, i.e., a large-capacity column, is used to allow a large amount of mobile phase to flow through it. With the mobile phase being supplied to the preparative column 142 at a constant flow rate, the injector 13 injects a predetermined amount of liquid sample selected by an autosampler (not shown) into the mobile phase at a predetermined timing. The injected liquid sample is introduced into the preparative column 142 on the mobile phase, and as it passes through the column 142, various compounds in the liquid sample are separated over time and eluted from its outlet end. The eluate is split by a splitter 15, with most of it introduced to the first detector 16 and a small portion to the second detector 18.

[0017] As the first detector 16, a non-destructive detector such as an ultraviolet-visible spectrometer is used. On the other hand, as the second detector 18, a destructive detector such as a mass spectrometer is used. The first detector 16 and the second detector 18 each detect compounds in the eluate and send the detection signal to the control / processing unit 2A and the preparative control unit 174 described later. The eluate that has passed through the first detector 16 is introduced into the fraction collector 17. The fraction collector 17 includes a preparative unit 170 including a preparative valve 171, a preparative nozzle 172, a preparative container 173, etc., and a preparative control unit 174, which separates and recovers the eluate containing the target compound.

[0018] The control and processing unit 2A consists of a computer including a CPU (Central Processing Unit), RAM (Random Access Memory), and storage. The control and processing unit 2A monitors detection signals from the first and second detectors 16 and 18 according to preset preparative conditions, and controls the on / off operation and delivery speed of the liquid delivery pumps 11a and 11b, the sample injection operation in the injector 13, and the operation of the preparative control unit 174, thereby separating compounds in a liquid sample and preparating an eluate containing one or more compounds. The preparative conditions may include one or more of the following: type of mobile phase, mobile phase flow rate (flow rate), sample injection volume, column temperature, gradient conditions, etc. Furthermore, the preparative conditions may also include the type of column and column size.

[0019] In the fraction collector 17, the preparative control unit 174 has the function of controlling the operation of the preparative unit 170 based on the detection signal (chromatogram signal) obtained from the first detector 16 or the second detector 18, but this function may be built into the control and processing unit 2A.

[0020] In this preparative LC apparatus, when preparating and purifying a specific target compound in a sample, the control and processing unit 2A controls the operation of each part according to preparative conditions, including gradient conditions as shown in Figure 15(a). Under these gradient conditions, the concentration of the organic mobile phase gradually increases from the initial concentration Cb at a constant slope S over time. Then, at a predetermined time t1, the concentration of the organic mobile phase rapidly increases to, for example, 90%, and is maintained constant thereafter. The slope S of the mobile phase change is constant so that the compound to be preparated is appropriately separated from other compounds, and so that various target compounds have roughly the same retention time (elution time). On the other hand, the initial concentration Cb of the organic mobile phase is changed according to the type of target compound, or more precisely, according to the retention time of the target compound in analytical-scale LC analysis. In Figure 15(a), the concentration changes of the mobile phase corresponding to different target compounds are shown by dotted lines, dashed lines, dashed lines, etc.

[0021] To isolate the target compound from a sample with high recovery rate and high purity, it is important to appropriately set the initial concentration Cb of the organic mobile phase (hereinafter, this initial concentration of the organic mobile phase may be simply referred to as the "initial mobile phase concentration") according to the retention time, which is the result of the LC analysis of the target compound. In the LC management system according to the present invention, in order to appropriately determine the initial mobile phase concentration, a calculation formula is provided, which is an approximate linear equation representing the relationship between the retention time in analytical-scale LC analysis and the initial mobile phase concentration, as shown in Figure 15(b), and the initial mobile phase concentration can be determined based on this calculation formula.

[0022] Next, an LC management system and an LC management method, which are embodiments of one embodiment of the present invention, and a computer program used to implement the method will be described.

[0023] [Configuration of the sorting condition determination system] Figure 1 is a schematic block diagram showing an example of a preparative condition determination system including the LC management system of this embodiment. In the figure, components that are the same as or equivalent to those in the system in Figure 2, which has already been described, are denoted by the same reference numerals to clarify the correspondence. This system includes an analysis / preparative unit 1, a control / processing unit 2, a preparative management unit 3, an operation unit 5, and a display unit 6. In the analysis / preparative unit 1, the main differences from the analysis / preparative unit 1A in Figure 2 are that the preparative column 142 is replaced by a separation column unit 14 that includes multiple columns, there is no fraction collector 17, and the second detector 18 is provided after the first detector 16. In this analysis / preparative unit 1, LC analysis using the preparative column 142 is performed, but preparative of the eluate is not performed, so the fraction collector 17 is unnecessary. Furthermore, since the eluate is not separated, the second detector 18 is placed after the first detector 16. However, as shown in Figure 2, the second detector 18 may also be arranged via a splitter 15 placed before the first detector 16.

[0024] The separation column section 14 consists of multiple types of columns, including an analytical column 141 used for analytical-scale LC analysis and a preparative column 142 used for preparative-scale LC analysis, as well as flow path switching valves 140 and 143. As mentioned above, typically, the analytical column 141 is a column with a lower volume, specifically a smaller inner diameter, compared to the preparative column 142. In other words, in this system, by switching the flow path using the flow path switching valves 140 and 143, LC analysis can be performed using different types of columns, including different volumes. Although Figure 1 only shows two mobile phase containers, 10a and 10b, it is possible to configure the system to allow switching between different types of mobile phases.

[0025] The control and processing unit 2 monitors detection signals from the first and second detectors 16 and 18 according to various preset analysis conditions, and controls the on / off operation and delivery speed of the liquid delivery pumps 11a and 11b, the sample injection operation in the injector 13, and the flow path switching operation by the flow path switching valves 140 and 143 to perform LC analysis on compounds in liquid samples under various analysis (and preparative) conditions and collects the LC analysis results. Meanwhile, the preparative management unit 3 determines the optimal preparative conditions for preparating the target compound based on the LC analysis results at the analysis scale and the LC analysis results at the preparative scale. The actual components of the control and processing unit 2 and the preparative management unit 3 are a computer 4 including a CPU, RAM, and storage, and their functions are realized by executing programs installed on the storage on the computer 4.

[0026] Figure 3 is a functional block diagram of the main components of the preparative management unit 3. As shown in Figure 3, the preparative management unit 3 includes a preparative condition optimization unit 30, a preparative condition optimization support unit 31, a storage unit 32, and the like. The preparative condition optimization unit 30 includes a preparative condition optimization database 301 used to find the optimal preparative conditions. The preparative condition optimization database 301 includes information on calculation formulas that show the relationship between the retention time of a compound and the initial concentration of the mobile phase in LC analysis on an analytical scale, as described above.

[0027] The preparative condition optimization support unit 31 includes a compound table creation unit 311, an identical compound search unit 312, a selection processing unit 313, an arithmetic formula calculation unit 314, and a display processing unit 315. The storage unit 32 includes an analysis data storage unit 321 that stores LC analysis results on an analytical scale, and a preparative data storage unit 322 that stores LC analysis results on a preparative scale. As shown in Figure 3, the analysis data storage unit 321 stores multiple LC analysis data files for a single sample, and each analysis data file includes a compound table that describes the retention time, peak area value, etc., for each identified compound. The preparative data storage unit 322 also stores multiple similar LC preparative data files for a single sample.

[0028] In the following explanation, the retention time in LC analysis at the analytical scale will be referred to as "analytical retention time" and will be simply written as "RT" or "analytical RT" in the figures. On the other hand, the retention time in LC analysis at the preparative scale will be referred to as "preparative retention time" and will be written as "preparative RT" in the figures.

[0029] In this analytical condition determination system, under the control of the control / processing unit 2, the analytical / preparative unit 1 performs analytical-scale LC analysis and preparative-scale LC analysis on multiple compounds, respectively. The resulting LC analysis data file and LC preparative data file, including the LC analysis results, are stored in the analytical data storage unit 321 and the preparative data storage unit 322. It is desirable that these multiple compounds have relatively similar properties from the perspective of LC separation, for example, similar affinity for water. This is because compounds with relatively similar properties from the perspective of LC separation can use a common calculation formula. In other words, it is difficult to use a common calculation formula for compounds with significantly different properties from the perspective of LC separation, and as will be described later, it is highly likely that different calculation formulas will be needed to determine the preparative conditions (in this case, the initial concentration of the mobile phase).

[0030] [How to derive the formula used to determine the parsing conditions] Here, we will first explain an example of calculating the formula using several known compounds as target compounds, each having a standard affinity for water (neither particularly hydrophilic nor hydrophobic). LC analysis on a single standard sample containing these multiple known compounds can be performed on both an analytical scale and a preparative scale to obtain LC analysis results for each of these compounds (hereinafter, the analytical scale LC analysis results will be referred to as "LC analysis results," and the preparative scale LC analysis results as "LC preparative results"). Alternatively, multiple standard samples containing one compound each can be prepared, and LC analysis on each of these samples can be performed on both an analytical scale and a preparative scale to obtain LC analysis results and LC preparative results for each of these compounds.

[0031] LC analysis on an analytical scale is performed using analytical column 141. That is, when performing LC analysis on an analytical scale, flow switching valves 140 and 143 are switched so that the mobile phase passes through analytical column 141 to reach the first detector 16, and the LC analysis is performed under predetermined gradient conditions. On the other hand, LC analysis on a preparative scale is performed using preparative column 142. That is, when performing LC analysis on a preparative scale, flow switching valves 140 and 143 are switched so that the mobile phase passes through preparative column 142 to reach the first detector 16, and the LC analysis is performed under predetermined gradient conditions. The conditions for LC analysis at this time are set to comprehensive conditions that are predetermined by the program and applicable to the LC analysis of various compounds, but the person in charge may select the conditions according to the compound to be preparated from among several pre-prepared analytical conditions.

[0032] Furthermore, as will be described later, when calculating the calculation formula, one LC analysis result is sufficient for a single target compound, but at least two LC preparative results are required. For this reason, preparative scale LC analysis is performed two or more times under different analytical conditions. Specifically, in preparative scale LC analysis, the initial mobile phase concentration is changed in multiple stages, and the retention time information of the target compound on the chromatogram obtained under each condition is stored in the preparative data storage unit 322 as the LC preparative result.

[0033] Next, the characteristic operations performed by the sorting condition optimization support unit 31 based on the data stored in the memory unit 32 will be explained with reference to Figures 4 to 14. Figure 4 is a flowchart showing an example of the operation and processing procedures when the sorting condition optimization support unit 31 determines the calculation formula, and Figures 5 to 14 show the display screens, etc., during those operations and processing.

[0034] When the operator performs a predetermined operation from the operation unit 5, the compound table creation unit 311 displays a file selection dialog on the screen of the display unit 6. The file selection dialog may include a list showing a list of analysis data files stored in the analysis data storage unit 321. The operator selects one or more analysis data files corresponding to the target compound to be used to create the calculation formula from this file list (step S1). In response to this selection operation, the compound table creation unit 311 obtains information on the name of the compound identified in the LC analysis and its analytical retention time (elution time) from the compound table stored in each selected analysis data file (step S2).

[0035] The compound table creation unit 311 sorts the target compounds in order of their acquired analytical retention times (step S3), and creates a compound candidate table in which the compound name, analytical data file name, and analytical retention time (RT) are listed on one line for each compound. The display processing unit 315 displays the analytical data selection screen 200 on the display unit 6 screen, as shown in Figure 5, on which the compound candidate table 201 is placed (step S4). In the example in Figure 5, the compound candidate table 201 displays the analytical data file names and analytical retention times for five target compounds, A to E.

[0036] The person in charge visually checks the compound candidate table 201, and if there are no problems, clicks the "Apply" button 202 located on the analysis data selection screen 200. On the other hand, if the listed compounds are not appropriate, they can cancel and select the analysis data file again. Alternatively, if they want to exclude some compounds from the compound candidate table 201, they can uncheck the checkbox 201a located in the row of the compound to be excluded on the table 201. When the "Apply" button 202 is clicked, the compound table creation unit 311 confirms the compounds in the compound candidate table 201 that are currently displayed (and have a checkmark in checkbox 201a) as the target compounds. Accordingly, the display processing unit 315 switches the screen on the display unit 6 to the preparation condition calculation screen 210, as shown as an example in Figure 6.

[0037] The preparative conditions calculation screen 210 contains a compound table 211 that includes the confirmed target compound. Below the compound table 211 are the "Preparative Data" button 213, the "Number of Samples for Each Algorithm" setting box 214, the "Target Elution Time" setting box 215, and the "Calculate" button 216. The operator sets the appropriate values ​​for the number of samples and target elution time for each algorithm in the setting boxes 214 and 215, respectively. Then, the operator clicks the "Preparative Data" button 213 to instruct the automatic acquisition of preparative data (Step S5).

[0038] In this context, "algorithm" refers to a method for calculating preparative conditions using mathematical formulas, and the specific differences between algorithms lie in the mathematical formulas used. Algorithms include normal algorithms for standard compounds, algorithms for highly hydrophobic compounds, and algorithms for highly hydrophilic compounds.

[0039] In response to the above instructions, the identical compound search unit 312 searches the preparative data storage unit 322 for a preparative data file containing LC preparative results for a compound identical to the target compound listed in the compound table 211 (step S6). Here, one of the following two methods can be used, or both can be used in combination, to identify the identical compound.

[0040] <Method A: Compound name search> When creating and registering a preparative data file, the person in charge should include the name of the compound targeted for LC analysis on a preparative scale in the file name. For example, if a preparative data file is obtained for a standard sample containing the compound "Methylparaben", the file name should be something like "Test_NH4HCO3_#01_Methylparaben.lcd", and it would be good to standardize this naming convention. The identical compound search unit 312 refers to the file name of the preparative data file to identify the preparative data file for the same compound as the target compound and retrieves the data stored in that preparative data file. In other words, in method A, the analytical data file and the preparative data file can be seen as being linked by the name of the compound. However, as mentioned above, a single standard sample may contain multiple types of compounds, so the correspondence between the analytical data file and the preparative data file is not necessarily one-to-one.

[0041] <Method B: Molecular weight search> The compound candidate table 201 on the analysis data selection screen 200 shown in Figure 5 is provided with a field for inputting the molecular weight of each compound. The person in charge inputs the known molecular weight information for each target compound in this compound candidate table 201. However, if the molecular weight information corresponding to a compound is included in the analysis data file, the same compound search unit 312 may acquire that molecular weight information along with the analysis retention time, etc., and automatically input it into the molecular weight field of the compound candidate table 201. Alternatively, a database that associates various compounds with molecular weights may be prepared in advance, and the molecular weight information corresponding to the target compound may be automatically acquired using that database and input into the molecular weight field of the compound candidate table 201. Furthermore, if the mass spectrum acquired by the mass spectrometer, which is the second detector 18, during LC analysis on an analytical scale is included in the analysis data file, the molecular weight information may be automatically extracted from that mass spectrum and input into the molecular weight field of the compound candidate table 201.

[0042] During LC analysis on a preparative scale, a mass spectrum is acquired by the mass spectrometer, which is the second detector 18, and the mass spectrum corresponding to the identified compound is stored in the preparative data file. Therefore, each preparative data file contains information about the mass spectrum. The identical compound search unit 312 then analyzes the mass spectra in each preparative data file stored in the preparative data storage unit 322 to estimate the molecular weight of the target compound and identifies the preparative data file containing a compound whose molecular weight matches that of the target compound within a predetermined tolerance range. Then, it acquires the data stored in the identified preparative data file. In other words, in this method B, the analysis data file and the preparative data file can be seen as being linked by the molecular weight of the compound.

[0043] Furthermore, the preparative data file containing LC preparative results for compounds identical to or presumed to be identical to the target compound can be identified not only by the two methods described above, but also by other methods. For example, if the preparative data file contains information that identifies the compound, such as the name of the identified compound, this information can be used to determine the identity of the compound. In addition to the compound name, information that can generally identify a compound, such as the chemical formula or CAS registry number, may also be used.

[0044] The identical compound search unit 312 identifies the corresponding preparative data file for each target compound listed in the compound table 211 using the procedure described above, and obtains information such as the preparative data file name, LC analysis results such as preparative retention time, and the initial mobile phase concentration, which is one of the analysis conditions. As described above, since preparative scale LC analysis is performed on a single compound under multiple different analysis conditions (such as initial mobile phase concentration), at least two or more preparative data files are identified for a single target compound, and information about those data files is obtained.

[0045] Based on the acquired information, the compound table creation unit 311 automatically inputs the preparative data file name, the initial mobile phase concentration during LC analysis on the preparative scale, and the preparative retention time for each target compound in the compound table 211 on the preparative condition calculation screen 210 (step S7). Figure 7 shows an example of the compound table 211 in which the preparative data file name, etc., have been added based on the search results for the same compound. In the figure, the added portion is indicated by the symbol 211A. In this example, two LC preparative results have been extracted for one target compound. That is, in this compound table 211, the LC analysis results and LC preparative results are displayed linked for each target compound, so the person in charge can visually check, for example, the relationship between the analysis retention time and the preparative retention time. However, at this point, the calculation of the calculation formula described later has not yet been performed, so the "Calculated B concentration" shown in Figure 7 is blank.

[0046] As mentioned above, in some cases, preparative scale LC analysis may be performed on a single compound under three or more different analytical conditions, resulting in the extraction of three or more LC preparative results for a single target compound. Figure 9 shows an example of such a case in compound table 211. In this example, four LC preparative results are extracted for both compound B and compound D. How to handle such cases will be discussed later.

[0047] As described above, once the analytical retention time, which is the LC analysis result, and the preparative retention time, which is the LC preparative result, are available for each target compound, the person in charge clicks the "Calculate" button 216 on the preparative condition calculation screen 210 to instruct the calculation of a formula that shows the relationship between the retention time in LC analysis on an analytical scale and the initial concentration of the mobile phase (step S8).

[0048] When deriving the above calculation formula, in principle, one LC analysis result (analytical retention time) and two LC separation results (separation retention times) under different conditions are required for each compound. Furthermore, while the number of compounds should be at least two, in order to obtain a calculation formula that can be commonly used for a group of compounds consisting of multiple compounds with similar properties, it is desirable to use the results of as many compounds as possible included in that group in calculating the formula. On the other hand, the compounds initially selected by the person in charge may include compounds that are not suitable for calculating the calculation formula, or may include LC separation results that are not suitable for calculating the calculation formula. Therefore, when calculating (or before calculating) the calculation formula, the selection of compounds or LC separation results can be done as follows.

[0049] For example, a target compound for which no corresponding preparative data file exists, or for which only one corresponding LC preparative result exists, is unsuitable as a compound to be used in the calculation of the formula. Therefore, such a target compound can be excluded from the calculation of the formula by having the person in charge uncheck the checkbox at the far left of the compound table 211 before the calculation of the formula. Alternatively, the selection processing unit 313 may automatically exclude such compounds (step S9).

[0050] The specific method for determining the calculation formula can be the method described in Patent Document 1. That is, first, for each target compound, the initial mobile phase concentration (referred to as "Calculated B Concentration" in Figure 6) is determined such that the retention time becomes the target elution time (the value set in the "Target Elution Time" setting box 215). Specifically, if there are two LC preparative results for a single target compound, such as compounds A to E shown in Figure 7, the calculation formula unit 314 uses the two preparative retention times and the actual initial mobile phase concentration in the preparative scale LC analysis (referred to as "Preparative B Concentration" in Figure 6) to calculate the initial mobile phase concentration such that the retention time becomes the target elution time using the following approximate formula shown in equation (1). Y = αX + β …(1) Here, X represents the retention time (elution time), and Y represents the initial mobile phase concentration at that time. α and β are coefficients obtained by substituting the measured preparative retention time and initial mobile phase concentration obtained for each target compound. α and β can be determined if data for at least two preparative retention times and initial mobile phase concentrations are available for each target compound. The value of the initial mobile phase concentration at which the retention time equals the target elution time is displayed, for example, in the "Calculated B Concentration" column of compound table 211 shown in Figure 7.

[0051] Next, a calculation formula is calculated that shows the relationship between the analytical retention time of multiple (five in the example shown in Figure 7) target compounds and the initial mobile phase concentration when the retention time obtained from the approximation formula (1) above becomes the target elution time. This calculation formula can be obtained by creating a graph with the retention time in analytical-scale LC analysis on the X axis and the initial concentration of the organic mobile phase on the Y axis, as shown in Figure 15(a), and then determining the function (linear function) that best fits that graph through regression analysis (step S10).

[0052] As shown in Figure 9 for compounds B and D, if there are three or more LC separation results (separation retention times) for a single target compound, the initial mobile phase concentration that results in the target elution time can be calculated using all of these separation retention times and initial mobile phase concentrations. Alternatively, for all combinations of selecting two of the three or more LC separation results, the initial mobile phase concentration that results in the target elution time can be calculated for each, and the combination that minimizes the error (residual) of the function obtained by regression analysis can be selected.

[0053] Furthermore, if the number of target compounds listed in the compound table 211 exceeds the number of samples specified in the "Number of samples for each algorithm" setting box 214, the selection processing unit 313 can perform the following processing to adjust the number of target compounds used to calculate the calculation formula to the specified number of samples. That is, for example, when obtaining a calculation formula by regression analysis, compounds whose plotted points on the graph deviate significantly from the straight line of the approximate calculation formula can be automatically excluded. In this case, it is preferable to display the numerical values ​​of the calculated B concentrations that have been excluded from the calculation on the compound table 211 in a manner that can be easily identified from other calculated B concentrations, for example, by using red text, and then automatically uncheck the check mark on the checkbox corresponding to that compound.

[0054] Alternatively, when determining the calculation formula, the selection processing unit 313 may ensure that the plot points on the graph are distributed as evenly as possible on the X or Y axis, in other words, exclude compounds corresponding to unevenly distributed plot points. In this case as well, it is advisable to display the numerical values ​​of the calculated B concentrations excluded from the calculation on the compound table 211 in a manner that makes them easily distinguishable from other calculated B concentrations, for example, by using red text, and to display the compounds that were adopted and those that were not adopted on the compound table 211 in a manner that makes them easily distinguishable, and then automatically uncheck the checkbox corresponding to the compound in question. By making the intervals between plot points on the graph nearly uniform in this way, it becomes easier to ensure the accuracy of the calculation formula.

[0055] Furthermore, the selection processing unit 313 may perform the following processing when calculating the arithmetic expression. The preparative retention time (preparative RT) for a given compound used in the calculation of the formula is preferably positioned to straddle the target elution time, that is, before and after the target elution time. However, it is possible that both preparative retention times may be either before or after the target elution time. In that case, the target elution time is located at a position extrapolated from the two preparative retention times, and in particular, the focus gradient for the target compound may not perform adequately, potentially leading to a decrease in the purity of the target compound or a decrease in the recovery rate of the target compound. Therefore, the selection processing unit 313 should warn the operator when calculating the formula if the target elution time is located at a position extrapolated from the preparative retention time for a given compound.

[0056] In other words, when the operator presses the "Calculate" button 216, the selection processing unit 313 determines whether, at that time, both of the preparative retention times for each target compound are located before or after the target elution time. If both of the preparative retention times are located before or after the target elution time, a red "!" mark is displayed in the column for the preparative retention time of that compound on the compound table 211, and a warning message, "Error: Extrapolation to target elution time," is displayed in a pop-up window. This allows the operator to understand that the calculation formula based on the preparative retention time value at that time cannot guarantee the accuracy of the preparative conditions, and prevents them from performing the calculation without realizing that extrapolation is occurring.

[0057] If a warning message like the one described above appears, the person in charge can resolve the extrapolation of the target elution time using one of the following methods.

[0058] First, when the operator right-clicks using the mouse included in the control unit 5, a right-click menu 220, as shown in Figure 12, pops up on the preparative condition calculation screen 210. The right-click menu 220 has four options: "Edit preparative RT," "Change data file," "Change target elution time," and "Delete row," and the operator can select any of these. Each of these will be explained below.

[0059] When the operator selects "Edit Preparative RT" in the right-click menu 220, the calculation formula unit 314 automatically changes the preparative retention time, which is currently extrapolated, to a value that is not extrapolated. Specifically, for example, the preparative retention time that is closer to the target elution time is automatically changed to target elution time - 0.1 or target elution time + 0.1. To indicate that the changed preparative retention time value is not a value obtained from the preparative data file, the text color is changed from the others, as shown in Figure 11, and a warning pop-up message "Caution: Value changed from data file" is temporarily displayed. Furthermore, the automatically changed value can be manually entered (changed) by the operator. This allows the operator to further correct the automatically changed value to an appropriate value at their own discretion after the preparative retention time value has been automatically changed.

[0060] When the user selects "Change Data File" in the right-click menu 220, the calculation formula unit 314 displays a preparative data selection dialog 230 as shown in Figure 12. This dialog 230 displays one of the data sets for creating the regression line on a single line. When the user selects a folder containing the preparative data file by operating the "..." button 232 located at the right end of this line, the identical compound search unit 312 automatically retrieves other preparative data files in which the same compound as the preparative data file before the change has been identified, and automatically retrieves the preparative data (initial concentration of organic mobile phase, preparative retention time) contained in those data files. It then creates and displays a list 231 of this preparative data. In the example in Figure 12, five new preparative data files and the preparative data within them are listed.

[0061] The person in charge checks the list 231, places a check mark next to the data for which the target elution time can be interpolated, and then clicks the "Apply" button 233. The compound table creation unit 311 accepts this operation and reflects the values ​​such as the preparative retention time for the specified row into the compound table 211 on the main preparative condition calculation screen 210. This allows for the selection of an appropriate preparative data file in which the preparative retention time is interpolated relative to the target elution time.

[0062] If the person in charge selects "Change Target Elution Time" in the right-click menu 220, the calculation unit 314 automatically enters recommended values ​​in the "Target Elution Time" setting box 215 on the preparative condition calculation screen 210 for all compounds in the compound table 211, values ​​that do not extrapolate the preparative retention time. These automatically entered values ​​can be manually edited by the person in charge.

[0063] If the user selects "Delete Row" in the right-click menu 220, the calculation unit 314 automatically deletes the extrapolated row (compound) in the compound table 211. The user then manually adds a new preparative data file as needed. If the user clicks the "Calculate" button 316 without adding a preparative data file, the calculation formula will be created with fewer compounds reflected in the formula.

[0064] As described above, once a calculation formula is obtained showing the relationship between retention time in analytical-scale LC analysis and the initial mobile phase concentration when the retention time becomes the target elution time, the display processing unit 315 displays a graph 217 representing this calculation formula in the upper right corner of the preparative condition calculation screen 210, as shown in Figure 8. Below the graph 217, the numerical information of the calculation formula corresponding to the graph 217 is displayed in Table 218. In this case, Table 218 includes the slope of the line on the graph 217 and the numerical value of the Y-intercept (Step S11). When the operator clicks the "Apply" button 219 in this state, the calculated calculation formula is finalized and registered in the preparative condition optimization database 310. Using this registered calculation formula, it becomes possible to determine the preparative conditions when preparating the target compound.

[0065] Specifically, in the preparative condition determination system shown in Figure 1, when determining the preparative conditions, an analytical column 141 is used to perform LC analysis on a standard sample containing the target compound to be preparated under predetermined analytical conditions. The control and processing unit 2 creates a chromatogram based on the data collected in this LC analysis, detects the peak corresponding to the target compound on the chromatogram, and determines the retention time. In the preparative management unit 3, the preparative condition optimization unit 30 uses the above calculation formula contained in the preparative condition optimization database 301 to determine the initial concentration value of the organic mobile phase that enables the preparative compound to be prepared at the target elution time. As shown in Figure 15(b), for example, if the measured retention time of the target compound is t0, the initial concentration value of the mobile phase that enables the preparative compound to be prepared at the target elution time can be determined from the calculation formula to be Cb0. Then, gradient conditions that change as shown by the solid line in Figure 15(a) with this value Cb0 as the initial concentration can be determined. Based on the preparative conditions thus determined, the target compound can be separated and purified near the target elution time by performing component separation using the preparative LC apparatus shown in Figure 2.

[0066] As described above, the preparative condition determination system makes it possible to create a calculation formula that shows the relationship between the retention time in analytical-scale LC analysis and the initial concentration of the organic mobile phase, which is used when determining the gradient condition, one of the preparative conditions, with simple operations, and make it available for use in the preparative condition determination work.

[0067] In particular, conventional systems, such as those described in Non-Patent Document 1, assumed that skilled personnel with specialized knowledge were responsible for creating the calculation formulas. As a result, the tasks of searching for LC analysis results and LC preparative results used to create the calculation formulas, inputting that data, and correcting or replacing LC preparative results when the calculation formulas were inappropriate or were expected to be inappropriate were extremely cumbersome. In contrast, the system proposed here can significantly simplify these tasks and improve work efficiency. Furthermore, it becomes possible for individuals with insufficient knowledge or limited experience in LC analysis to perform the tasks, making it easier for, for example, the instrument user to create the calculation formulas. Moreover, it prevents the creation of calculation formulas using inappropriate data, thereby improving the accuracy of the calculation formulas and increasing the recovery rate and purity when preparating and purifying the target compound.

[0068] [Differentiation] The above explanation described an example of changing the gradient conditions as a preparative condition, but other preparative conditions such as the mobile phase flow rate (or flow rate), sample injection volume, and column volume may also be changed. Of course, it is also possible to change more than one preparative condition.

[0069] Furthermore, in the above explanation, the relationship between retention time in analytical-scale LC analysis and the initial concentration of the organic mobile phase during preparative sampling was expressed by a single calculation formula, as shown in Graph 217 in Figure 8 or the graph in Figure 15(b). However, multiple calculation formulas may be used depending on the properties and characteristics of the target compound. In other words, it may be possible to selectively use different algorithms, not just the normal algorithm represented by the numerical values ​​in Table 218 shown in Figure 8.

[0070] Specifically, the calculation formula using the normal algorithm is for compounds with a standard affinity for water, but separate calculation formulas may be created for compounds that are extremely hydrophilic and / or extremely hydrophobic. As an example, Figures 13 and 14 illustrate the case where, in addition to the normal algorithm, a calculation formula using a hydrophobic algorithm for compounds with extremely high hydrophobicity is created.

[0071] In this case, when selecting the target compounds to be used in creating the calculation formula, the person in charge selects, for example, compounds A, B, C, D, and E, which have standard affinity for water, as well as other compounds F, G, H, J, and K, which have extremely high hydrophobicity. In this case, an example of compound table 211 created by automatically obtaining LC separation results is shown in Figure 13. In Figure 13, the data indicated by symbol 211B pertains to the group of compounds with standard affinity for water, while the data indicated by symbol 211C pertains to the group of compounds with extremely high hydrophobicity.

[0072] In this case, the calculation of the formula using the procedure described above is performed for each group of compounds with different properties, and a corresponding formula is calculated for each. As a result, a graph 217 and a table 218, as shown in Figure 14, are displayed on the right side of the preparative condition calculation screen 210. In graph 217, the plots marked with black circles represent the initial mobile phase concentrations corresponding to the group of compounds with standard hydrophilicity (compounds A, B, C, D, E), and a straight line of approximation is calculated from these plots, shown as a solid line. On the other hand, the plots marked with white circles represent the initial mobile phase concentrations corresponding to the group of compounds with extremely high hydrophobicity (compounds F, G, H, J, K), and a straight line of approximation is calculated from these plots, shown as a dotted line. Table 218 shows the slope and Y-intercept of each formula numerically, as well as the retention time corresponding to the intersection of the two straight lines of approximation.

[0073] When multiple calculation formulas (algorithms) are registered in the preparative condition optimization database 301, one of the calculation formulas can be used depending on the properties of the compound to be preparated to determine the initial concentration of the mobile phase during preparative extraction from the measured retention time in analytical-scale LC analysis. This makes it possible to determine more appropriate preparative conditions according to the properties of the compound.

[0074] Furthermore, the above embodiments and modifications are merely examples of the present invention, and it is clear that any further changes, additions, or deletions made within the scope of the present invention will still be included in the claims of this patent application.

[0075] [Various forms] Those skilled in the art will understand that the exemplary embodiments described above are specific examples of the following embodiments.

[0076] (Section 1) One aspect of the LC management system according to the present invention is a management system for acquiring information used when determining analytical conditions for operating an LC device, A first storage unit that stores one or more first analysis result files containing first analysis results obtained by performing LC analysis on a predetermined sample containing one or more compounds under first analysis conditions, A second storage unit that stores multiple second analysis result files, including a second analysis result obtained by performing LC analysis on a predetermined sample containing one or more compounds under second analysis conditions where the mobile phase flow rate or sample injection volume is greater than that of the first analysis conditions; A search unit searches for a second analysis result in the second analysis result file stored in the second storage unit that corresponds to the same compound as the first analysis result in the first analysis result file stored in the first storage unit, Based on the search results by the search unit, the association information creation unit creates association information for each compound, which associates the first analysis result with the second analysis result or associates the first analysis result file with the second analysis result file. A display processing unit that displays the aforementioned association information on a screen, It is equipped with.

[0077] (Section 2) One aspect of the LC management method according to the present invention is a management method that uses a computer to acquire information used when determining analytical conditions for operating a liquid chromatograph apparatus, wherein the computer is A first step of storing one or more first analysis result files containing first analysis results obtained by liquid chromatographic analysis of a predetermined sample containing one or more compounds under first analytical conditions, A second step of storing multiple second analysis result files, each containing a second analysis result obtained by performing liquid chromatography analysis on a predetermined sample containing one or more compounds under second analysis conditions where the mobile phase flow rate or sample injection volume is greater than that of the first analysis conditions. A third step of searching the second analysis result file for a second analysis result that corresponds to the same compound as the first analysis result in the first analysis result file. A fourth step is to create association information for each compound based on the results of the search, which associates the first analysis result with the second analysis result or associates the first analysis result file with the second analysis result file, and The fifth step is to display the aforementioned association information on the display screen. Execute this.

[0078] In the LC management system described in paragraph 1 and the LC management method described in paragraph 2, LC includes preparative LC. The first and second analytical conditions are conditions that affect the separation performance in LC, and may include one or more of the following: column type (type of packing material, particle size, etc.), column dimensions (inner diameter, length), mobile phase type, mobile phase flow rate (flow rate), sample injection volume, column temperature, gradient conditions, etc. The first and second analytical results may include various information corresponding to the compounds in the sample obtained from data acquired by the LC detector and data processing based on that data. For example, in addition to elution time (retention time) and peak area (or height), if the detector is a mass spectrometer, the first and second analytical results may include information such as the mass spectrum obtained at the elution time of the compound and the molecular weight determined from the mass spectrum.

[0079] The LC management system described in paragraph 1 and the LC management method described in paragraph 2 automate the process of searching for and relating first and second analysis results for the same compound obtained under different analytical conditions, thus eliminating the need for the operator to perform these tasks manually. Furthermore, the operator can easily compare the first and second analysis results for the same compound based on the correlation information displayed on the screen. As a result, the LC management system described in paragraph 1 and the LC management method described in paragraph 2 simplify the operator's work when obtaining calculation formulas and equivalent information used to determine appropriate preparative conditions through scale-up, for example, improving work efficiency and reducing errors, thereby enabling the setting of more appropriate preparative conditions.

[0080] (3) In the LC management method described in paragraph 2, at least one of the first analysis result and the second analysis result includes a mass spectrum, and the computer may, in the third step, determine the identity of the compound associated with the first analysis result and the compound associated with the second analysis result by comparing the mass spectra or by comparing the molecular weight estimated from the mass spectrum with information on the molecular weight of each compound.

[0081] In the LC management method described in Section 3, the identity of a compound is determined based on information such as the peak pattern of the mass spectrum and molecular weight. Therefore, even if the compound name is unknown, information on compounds that are highly likely to be the same can be obtained and related information can be displayed.

[0082] (Paragraph 4) In the LC management method described in Paragraph 2, the computer may, in the third step, use information that identifies the compounds contained in the first analysis result file and the second analysis result file, respectively, to determine the identity of the compound associated with the first analysis result and the compound associated with the second analysis result.

[0083] Here, "information contained in the first analysis result file and the second analysis result file, respectively" refers to all information related to the file, including not only the data stored in the file, but also the file name and file attributes used to identify the file. Furthermore, "information identifying the compound" is typically the compound name, but any information that can identify an individual compound is acceptable, such as the CAS registry number or chemical formula.

[0084] The LC control method described in paragraph 3 above requires mass spectral information to determine the identity of a compound, and therefore requires the use of a device that uses a mass spectrometer as a detector when acquiring the data. In contrast, the LC control method described in paragraph 4 determines the identity of a compound using information that identifies the compound, such as the compound name, and does not require information on the molecular weight of the compound. Therefore, it can be applied to devices that use ultraviolet-visible spectrophotometers or the like as detectors.

[0085] (Article 5) A method for controlling LC as described in any one of Articles 2 to 4, wherein the first analytical conditions are the analytical conditions for liquid chromatography analysis using a normal analytical column, and the second analytical conditions are the analytical conditions for liquid chromatography analysis using a preparative column.

[0086] According to the LC control method described in Section 5, preparative conditions that allow for appropriate scaling up from an analytical scale to a preparative scale for the preparative and purification of large quantities of target compounds can be easily determined.

[0087] (Item 6) A method for managing LC as described in any one of items 2 to 5, wherein the plurality of second analysis result files are obtained by performing liquid chromatography analysis on the same compound under a plurality of different second analysis conditions, and the computer may, in the third step, search for a plurality of second analysis results associated with a single compound, and in the fourth step, create a list as association information for each compound, which associates the first analysis result with the plurality of second analysis results.

[0088] (Section 7) In the LC management method described in Section 6, the first and second analytical results include retention time information, and the table may include, for each compound, the retention time under the first analytical conditions and multiple retention times under the second analytical conditions.

[0089] In the LC control method described in Section 7, multiple retention times under different analytical conditions are associated with a single compound. By utilizing this information on multiple retention times, it is possible to estimate a second analytical condition such that the retention time becomes a target elution time. Using this result, information such as a calculation formula showing the relationship between the retention time in the LC analysis under the first analytical condition and the second analytical condition can be obtained. Based on this information, it is possible to determine the second analytical condition for scale-up from the actual LC analysis results under the first analytical condition.

[0090] (Clause 8) In the LC control method described in paragraph 6 or 7, the first analytical conditions and the second analytical conditions each include information on the initial concentration of one of the mobile phases in gradient separation, and the table may include at least the initial concentration of the one of the mobile phases in the second analytical conditions.

[0091] According to the LC control method described in Section 8, for example, for each compound, it is possible to estimate the initial concentration of the mobile phase such that the retention time becomes a target elution time under conditions where the mobile phase flow rate is higher or the sample injection volume is higher than the first analytical conditions. This makes it possible to obtain information such as a calculation formula showing the relationship between the retention time and the initial concentration of the mobile phase in LC analysis under the first analytical conditions, and based on this information, the initial concentration of the mobile phase to be used when scaling up can be determined from the actual LC analysis results under the first analytical conditions.

[0092] (Section 9) A method for managing LC as described in any one of Sections 6 to 8, wherein the computer further performs a step of setting a target retention time for the compound to be separated, and in the fourth step, if there are three or more retention times associated with a single compound under the second analytical conditions, and there are multiple retention times that are located temporally before and after the target retention time, and if there are multiple retention times that are located temporally before or after the target retention time, the two selected retention times can be shown on the list in a way that makes them distinguishable from the other retention times by keeping only the retention time that is closer to the target retention time.

[0093] According to the LC control method described in Section 9, the accuracy of estimation can be improved when estimating the initial concentration of the mobile phase, for example, so that the retention time becomes the set target retention time. This also improves the accuracy of information such as calculation formulas that show the relationship between the retention time in LC analysis under the first analytical conditions and the second analytical conditions, which are used to determine the second analytical conditions when scaling up. For example, the target compound can be separated and purified with higher recovery and purity.

[0094] (Clause 10) The LC management method described in paragraph 9, wherein the computer may, in the fifth step, display the target holding time together with the list on the display screen. Furthermore, in the fifth step, the computer may be able to change the target holding time displayed on the display screen in accordance with the operator's actions.

[0095] According to the LC management method described in paragraph 10, the person in charge can easily determine whether the target retention time set at that time and the retention time, which is the result of the LC analysis under the second analysis condition, are appropriate data by comparing them on the display screen.

[0096] (Item 11) A method for managing LC as described in any one of items 6 to 10, wherein the computer further performs the step of creating a graph that reflects the relationship between the analysis conditions and the analysis results, using the first analysis results and a plurality of second analysis results which are associated with all or one or more specific compounds listed in the table, and in the fifth step, the graph is displayed on the display screen together with the table.

[0097] The graph that reflects the relationship between the analytical conditions and the analytical results, as referred to here, is, for example, a graph showing the relationship between the retention time and the initial concentration of the mobile phase in LC analysis under the first analytical conditions. According to the LC management method described in Section 11, for example, the person in charge can easily determine whether the calculation formula, which shows the relationship between the retention time and the initial concentration of the mobile phase in LC analysis under the first analytical conditions and is used to determine the preparative conditions, is valid by checking it in graph form.

[0098] (Clause 12) A method for managing LC as described in paragraph 9 or 10, wherein the computer further performs the step of setting a target retention time for the compound to be separated; in the fourth step, it determines whether all of the retention times under the second analytical conditions associated with a single compound are located before or after the target retention time; and in the fifth step, if it is determined that all of the retention times under the second analytical conditions are located before or after the target retention time, a warning is displayed on the list.

[0099] If all retention times under a second analytical condition associated with a single compound are either earlier or later than the target retention time, extrapolation is necessary to determine the second analytical condition that will result in the target retention time. This inevitably leads to lower accuracy compared to interpolation. In contrast, the LC control method described in Section 12 allows the person in charge to be informed in advance that extrapolation will be performed. If necessary, the person in charge can take appropriate measures, such as changing the target retention time, to avoid extrapolation. This improves the accuracy of the calculation formula showing the relationship between retention time and the initial concentration of the mobile phase in LC analysis under the first analytical condition, and allows for more appropriate preparative conditions based on that formula. [Explanation of Symbols]

[0100] 1, 1A…Analysis / Preparation section 10a, 10b...mobile phase container 11a, 11b... Liquid transfer pumps 12... Mixer 13…Injector 14...Separation column section 140, 143... Flow path switching valve 141…Analytical column 142… Preparative column 15… Splitter 16…First detector 17…Fraction Collector 170...Preparative section 171... Pre-partition valve 172... Dispensing nozzle 173…Preparative container 174... Distributed Control Unit 18…Second detector 2, 2A…Control / Processing Unit 3…Preparative separation management department 30... Optimization of sorting conditions 301... Preparative Condition Optimization Database 31... Optimization Support Unit for Sorting Conditions 311... Compound Table Creation Department 312...Same compound search department 313...Selection Processing Unit 314... Arithmetic expression calculation unit 315...Display Processing Unit 32...Storage section 321...Analysis data storage unit 322... Data storage unit 4… Computer 5...Operation unit 6...Display section

Claims

1. A management system for acquiring information used when determining the analytical conditions for operating a liquid chromatography apparatus, A first storage unit that stores one or more first analysis result files containing first analysis results obtained by liquid chromatographic analysis of a predetermined sample containing one or more compounds under first analysis conditions, A second storage unit that stores multiple second analysis result files, including a second analysis result obtained by performing liquid chromatography analysis on a predetermined sample containing one or more compounds under second analysis conditions in which the mobile phase flow rate or sample injection volume is greater than that of the first analysis conditions; A search unit searches for a second analysis result in the second analysis result file stored in the second storage unit for a second analysis result in the second analysis result file stored in the second storage unit for a second analysis result in the second analysis result file stored in the first storage unit for a second analysis result in the second analysis result file stored in the first storage unit, Based on the search results from the search unit, the association information creation unit creates association information for each compound, which associates the first analysis result with the second analysis result or associates the first analysis result file with the second analysis result file. A display processing unit that displays the aforementioned association information on a screen, A liquid chromatography management system equipped with [specific features / features].

2. A management method for acquiring information used when determining analytical conditions for operating a liquid chromatograph apparatus using a computer, wherein the computer is: A first step of storing one or more first analysis result files containing a first analysis result obtained by liquid chromatographic analysis of a predetermined sample containing one or more compounds under first analytical conditions, A second step of saving multiple second analysis result files, which include a second analysis result obtained by performing liquid chromatography analysis on a predetermined sample containing one or more compounds under second analysis conditions where the mobile phase flow rate or sample injection volume is greater than that of the first analysis conditions. A third step of searching the second analysis result file for a second analysis result that corresponds to the same compound as the first analysis result in the first analysis result file. A fourth step is to create association information for each compound, based on the results of the search, which associates the first analysis result with the second analysis result or associates the first analysis result file with the second analysis result file, and A fifth step is to display the aforementioned association information on the display screen. How to manage a liquid chromatograph that performs this operation.

3. At least one of the first analysis result and the second analysis result includes a mass spectrum. The liquid chromatograph management method according to claim 2, wherein in the third step, the computer determines the identity of the compound associated with the first analysis result and the compound associated with the second analysis result by comparing mass spectra with each other, or by comparing the molecular weight estimated from the mass spectra with information on the molecular weight of each compound.

4. The liquid chromatograph management method according to claim 2, wherein in the third step, the computer uses information that identifies the compounds contained in the first analysis result file and the second analysis result file, respectively, to determine the identity of the compound associated with the first analysis result and the compound associated with the second analysis result.

5. The liquid chromatograph control method according to claim 2, wherein the first analytical conditions are the analytical conditions for liquid chromatographic analysis using a normal analytical column, and the second analytical conditions are the analytical conditions for liquid chromatographic analysis using a preparative column.

6. Multiple of the aforementioned second analysis result files were obtained by performing liquid chromatography analysis on the same compound under multiple different second analysis conditions. The liquid chromatograph management method according to claim 2, wherein in the third step, the computer searches for a plurality of second analysis results associated with a single compound, and in the fourth step, for each compound, a list is created as association information that associates the first analysis result with the plurality of second analysis results.

7. The liquid chromatograph control method according to claim 6, wherein the first and second analysis results include retention time information, and the table includes, for each compound, the retention time under the first analysis conditions and a plurality of retention times under the second analysis conditions.

8. The first and second analytical conditions each include information on the initial concentration of one of the mobile phases in gradient separation. The liquid chromatograph control method according to claim 7, wherein the table includes at least the initial concentration of one of the mobile phases under the second analytical conditions.

9. The computer further performs the step of setting a target retention time for the compound to be separated, The liquid chromatograph management method according to claim 7, wherein in the fourth step, if three or more retention times are associated with a single compound under the second analytical conditions, and there are multiple retention times that are located temporally before and after the target retention time, and if there are multiple retention times that are located temporally before or after the target retention time, the method further comprises selecting two retention times by keeping only the retention time that is closer to the target retention time, and then indicating these two selected retention times in the table in a way that allows them to be distinguished from the other retention times.

10. The liquid chromatograph management method according to claim 9, wherein the computer displays the target holding time together with the list on a display screen in the fifth step.

11. The computer further performs the step of creating a graph that reflects the relationship between the analysis conditions and the analysis results, using the first analysis results and the multiple second analysis results which are associated with all or one or more specific compounds listed in the table. The liquid chromatograph management method according to claim 6, wherein in the fifth step, the graph is displayed on the display screen together with the table.

12. The computer further performs the step of setting a target retention time for the compound to be separated, A liquid chromatograph management method according to claim 7, wherein in the fourth step, it is determined whether all of the retention times under the second analytical conditions associated with a single compound are located before or after the target retention time, and in the fifth step, if it is determined that all of the retention times under the second analytical conditions are located before or after the target retention time, a warning is displayed on the list.

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