WO2014068786A1

WO2014068786A1 - Chromatographic analyzing device

Info

Publication number: WO2014068786A1
Application number: PCT/JP2012/078618
Authority: WO
Inventors: 一真前田
Original assignee: 株式会社島津製作所
Priority date: 2012-11-05
Filing date: 2012-11-05
Publication date: 2014-05-08

Abstract

When an analyst gives instruction for the number of samples and the location of the samples on a rack to discover suitable separation conditions (mobile phase and column type) in order to separate a target compound (S1), an analysis schedule is created that switches the analysis order so that analysis of a plurality of samples under the same separation conditions are performed consecutively in order to minimize the number of washings required each time the separation conditions are changed, and then analysis is performed accordingly (S2, S3). In addition, when a different analyst makes a reservation for analysis while an analysis is being performed (S1A), the analysis schedule including the unanalyzed sample is readjusted (S5). Thus, the need to change columns or mobile phases manually disappears, and the burden on the analyst is dramatically reduced. In addition, the overall time required for analysis is also reduced because the number of washings, which require time, is reduced.

Description

Chromatographic analyzer

The present invention relates to a chromatographic analyzer such as a liquid chromatograph (LC) device or a gas chromatograph (GC) device, and in particular, an analysis condition for collecting a target compound contained in a sample with high purity in a preparative LC device. The present invention relates to a chromatographic analyzer suitable for determination.

When researching, developing, or manufacturing pharmaceutical products, it is necessary to separate and purify the target compound with high purity from a mixture or natural extract containing various compounds produced by chemical synthesis reactions, etc. There is. For these purposes, a preparative LC apparatus that fractionates and collects a plurality of compounds contained in a liquid sample using a high performance liquid chromatograph (HPLC) apparatus has been widely used (for example, Patent Document 1). Generally, in LC analysis, various columns having different characteristics are used, and various mobile phases are also used. Since the separation characteristics of the compounds contained in the sample vary greatly depending on the combination of the column and mobile phase, the target compound in a sample can be separated with high purity, that is, with as little overlap of other compounds (contaminants) as possible. In order to obtain a sample, it is important to set the separation conditions (mainly the type of column and the type of mobile phase) that can best separate the target compound for each sample.

In this way, in order to search for the optimum separation conditions for the target compound for each sample, conventionally, an analyst performs an operation of switching between the mobile phase and the column, and all possible combinations of the mobile phase and the column are considered. LC analysis is performed on one sample and the result is used to determine which combination is optimal. Usually, the combination of the mobile phase and the column is at least about ten, and when it is large, the number is several tens. In particular, the number of samples to be processed per se is considerably large when conducting research and development of pharmaceuticals. Therefore, the task of searching for the optimum separation condition for the target compound for each sample is unavoidably time-consuming and time-consuming, which is a major factor that hinders the efficiency of drug discovery.

JP 2010-8047 A

The present invention has been made in view of the above problems, and the object of the present invention is to enable high-purity fractionation, for example, when fractionating a target compound in a sample using a preparative LC apparatus. It is an object of the present invention to provide a chromatographic analyzer capable of reducing the labor of an analyst required for finding an optimum separation condition and reducing the work time.

In order to solve the above problems, the present invention includes a column for separating compounds contained in a sample in a time direction, a mobile phase supply unit for supplying a mobile phase to the column, and a mobile phase supply unit. In a chromatographic analyzer comprising: a sample introduction part for introducing a sample into a mobile phase supplied to the column; and a detection part for detecting each compound in the sample eluted from the column.
a) a separation condition switching unit that sequentially switches the separation conditions among a plurality of separation conditions prepared in advance for one or more separation elements that affect the separation state of the target compound;
b) an analysis control unit that repeatedly introduces the same sample by the sample introduction unit while switching the separation condition by the separation condition switching unit, and performs chromatographic analysis of the same sample under each separation condition;
c) Chromatography for preparing chromatograms under different separation conditions based on data obtained by the detection unit in a plurality of chromatographic analyzes on the same sample performed under the control of the analysis control unit. Gram creation part,
And a separation condition suitable for the target compound in the sample can be searched using a plurality of chromatograms created by the chromatogram creation unit.

When the chromatographic analyzer according to the present invention is an LC apparatus, the mobile phase is an eluent, and the mobile phase supply unit typically includes a liquid feed pump. On the other hand, when the chromatographic analyzer according to the present invention is a GC device, the mobile phase is a carrier gas, and the mobile phase supply unit includes a flow rate regulator or a pressure regulator such as a mass flow controller.

In general, when a sample contains a plurality of compounds having various properties, the major factors that affect the separation state of the compounds are the separation characteristics of the column and the polarity of the mobile phase.
Therefore, as one aspect of the present invention, one of the separation elements is a column, the column is of a different type from the plurality of separation conditions, and the separation condition switching unit has a column used for chromatographic analysis. It can be set as the structure which is the column switching part to switch.

As another aspect of the present invention, one of the separation elements is a mobile phase, the mobile phase is different in type from the plurality of separation conditions, and the separation condition switching unit is connected to the mobile phase supply unit. And it can also be set as the structure which is a flow-path switching part which switches the mobile phase supplied to a column.

Furthermore, as another aspect of the present invention, one of the separation elements is a mobile phase, and the mixing ratio and the temporal mixing thereof when mixing a plurality of mobile phases different from the plurality of separation conditions. A plurality of gradient conditions with different ratio changes, and the separation condition switching unit is in the mobile phase supply unit and controls the operation of a liquid feed pump that feeds a plurality of mixed mobile phases. It can also be set as the structure which is a pump control part which changes flow volume.

In the chromatographic analyzer according to the present invention, for example, different types of columns and different types of mobile phases are automatically and sequentially switched under the control of the analysis control unit, and chromatographic analysis is performed on the same sample. The chromatogram creation unit creates a chromatogram based on the data obtained by performing multiple chromatographic analyzes on the same sample. For example, when the type of column and the type of mobile phase are different, the separation status of a plurality of compounds contained in the sample is changed, which is reflected in the peak overlap status on the chromatogram. Therefore, by confirming whether the chromatogram peak of the target compound overlaps with other peaks or is an isolated peak in multiple chromatograms under different separation conditions for the same sample, for example, the target compound has a high purity. The most suitable separation conditions can be found.

In the chromatographic analyzer according to the present invention, preferably,
An input unit for the user to specify a plurality of samples to be analyzed in series;
When a plurality of samples to be analyzed in series are specified through the input section, the sample and the separation conditions are combined so that chromatographic analysis is continuously performed on the plurality of samples under the same separation conditions. A schedule creation unit for creating an analysis schedule;
The analysis control unit may be configured to perform chromatographic analysis according to the analysis schedule created by the schedule creation unit.

When the mobile phase or column used for chromatographic analysis is changed, it is necessary to wash the flow path including the column (including column equilibration) in order to prevent column deterioration and contamination. As described above, if an analysis schedule is set so that chromatographic analysis is continuously performed on a plurality of samples under the same separation condition, the analysis is performed during the period when the analysis is performed under the same separation condition. Since it is not necessary to clean the flow path, the number of times of cleaning can be reduced. In general, the time required for cleaning the flow path is so long that it cannot be ignored compared with the actual analysis execution time. Therefore, by reducing the number of times of washing, the total time required for a series of analyzes on a plurality of samples can be shortened. In addition, although the washing promotes the deterioration of the column, the life of the column can be extended by reducing the number of washings.

Moreover, in the chromatographic analyzer having the above configuration,
The input unit allows the user to specify additional one or more samples even during chromatographic analysis,
When the input of the sample to be analyzed is instructed by the input unit, the schedule creation unit, for the sample that has not been analyzed in the analysis schedule being executed and the sample that has been additionally instructed, under the same separation condition Re-adjust the combination of sample and separation conditions to correct the analysis schedule so that chromatographic analysis on multiple samples is performed continuously,
The analysis control unit may be configured to continue the chromatographic analysis in accordance with the analysis schedule modified by the schedule creation unit.

According to this configuration, for example, even when an analyst is executing an analysis in the apparatus, another analyst can register the analysis of the sample to be analyzed. The analysis schedule is automatically adjusted for the best analysis efficiency. Therefore, for example, when a plurality of analysts share a single apparatus to perform compound isolation work, the overall work throughput can be improved.

In the chromatographic analyzer according to the present invention, in the configuration further comprising a sample selection unit that selects a designated sample from a plurality of samples accommodated in a rack and supplies the sample to the sample introduction unit.
When the user designates or adds a sample, it is preferable to display on the display screen a visually distinguishable sample storage position that can be used in the rack and a sample storage position that cannot be used.

Thus, even when a plurality of analysts share one apparatus, the analysts can proceed with the analysis work efficiently without confusing the sample.

In the chromatographic analyzer according to the present invention, preferably,
The detection unit is a mass spectrometer that repeatedly acquires mass spectrum data,
The input unit can set the molecular weight of the target compound or the mass-to-charge ratio characterizing the compound for each sample,
A peak extraction unit for identifying a chromatogram peak including a significant mass spectrum peak corresponding to the molecular weight or mass-to-charge ratio set in the input unit based on the mass spectrum data obtained by the mass spectrometer; It may be configured.

Furthermore, in the above configuration, the chromatogram creation unit displays the created chromatogram in a form in which the chromatogram peak identified by the peak extraction unit and other chromatogram peaks can be visually discerned. It is preferable to include a drawing processing unit to be displayed above.

Here, the mass spectrometer is typically a quadrupole mass spectrometer or a triple quadrupole mass spectrometer. In this configuration, the chromatogram is typically a total ion chromatogram. The “significant mass spectrum peak” is a peak whose intensity value of a mass spectrum peak having a molecular weight or a mass-to-charge ratio set in the input unit exceeds a predetermined threshold value, for example. This threshold value may be a default value or a value specified by the user.

In the chromatographic analyzer having the above configuration, the chromatogram peak specified by the peak extraction unit is a peak that is highly likely to be derived from the target compound. Therefore, by determining whether or not this chromatogram peak is in an isolated state, an optimal separation condition can be found. In particular, by displaying only the chromatogram peak identified by the peak extraction unit with a color different from that of the other chromatogram peaks, the analyst can easily and without error make a chromatogram derived from the target compound on the display screen. Gram peaks can be grasped, and it can be judged at a glance whether or not the separation conditions are appropriate.

Furthermore, it is more preferable that the chromatogram creation unit includes a drawing processing unit that displays a plurality of chromatograms obtained under different separation conditions for one sample side by side or superimposed on a display screen.

According to this configuration, the analyst can check the separation status of the chromatogram peak derived from the target compound under different separation conditions at a glance. For example, the optimal separation for separating the target compound with high purity is possible. Conditions can be found more easily.

According to the chromatographic analyzer according to the present invention, when searching for an optimal separation condition that enables high-purity fractionation, for example, an analyst himself / herself manually switches between a column and a mobile phase. Since it is not necessary to perform the analysis, it is not necessary for the analyst to be in the vicinity of the apparatus during the series of analysis, and the troublesome time for the analyst can be greatly reduced, and the time required for the analysis can be shortened. In particular, when there are multiple samples to be analyzed under the same separation conditions, the number of times the channel is washed is reduced by setting an analysis schedule so that the analysis of the multiple samples is performed continuously. Analysis time can be further reduced.

Furthermore, a mass spectrometer is used as a detection unit, and a chromatogram peak including a significant mass spectrum peak corresponding to a mass-to-charge ratio characterizing a target compound is found based on mass spectrum data obtained by the mass spectrometer. By clarifying this on the chromatogram, the analyst can grasp at a glance the chromatogram peak derived from the target compound and can immediately determine whether the separation conditions at that time are appropriate.

The block diagram of the principal part of the liquid chromatograph mass spectrometer (LC / MS) which is one Example of the chromatograph analyzer which concerns on this invention. The flowchart which shows control / processing of the operation | movement for characteristic separation condition search in LC / MS of a present Example. The figure which shows an example of the display screen at the time of analysis reservation setting. The figure which shows an example of the created analysis schedule. The figure which shows an example of the display screen during analysis execution. The figure which shows an example of a part of display screen at the time of an additional analysis reservation setting. The figure which shows an example of the analysis schedule after the schedule adjustment with respect to an additional analysis reservation. The figure which shows an example of the display screen of the analysis report after completion | finish of analysis.

Hereinafter, a liquid chromatograph mass spectrometer (LC / MS) which is an embodiment of a chromatographic analyzer according to the present invention will be described with reference to the accompanying drawings. FIG. 1 is a configuration diagram of a main part of the LC / MS of this embodiment.

This LC / MS is a first switching valve for selecting one of the four types of mobile phases A1 to A4 stored in the four mobile phase containers 1 and the cleaning liquid stored in the cleaning liquid container 2. 3 and a second switching valve 4 for selecting any one of the four types of mobile phases B1 to B4 stored in the four mobile phase containers 1 and the cleaning liquid stored in the cleaning liquid container 2; , The first liquid pump 5 and the second liquid pump 6 for sucking and feeding the solution selected by the switching valves 3 and 4 respectively, and the mobile phase fed by the liquid pumps 5 and 6 are mixed. A mixer 7, an injector 8 for injecting a sample into the mobile phase sent through the mixer 7, and a single sample designated from a number of samples prepared on a sample rack (not shown). Suction and supply to injector 8 An autosampler 9, six types of columns 11 (11a to 11f), and a third switching valve 10 and a fourth switch arranged on the inlet side and the outlet side of the column 11 in order to select a column to be used for LC analysis. A switching valve 12, an atmospheric pressure ionization mass spectrometer 13 for detecting a compound in the eluate from the column 11, a switching

valve

3, 4, 10, 12 or a

liquid feed pump

5, 6, an autosampler 9, a mass spectrometer Analysis control unit 14 for controlling operations such as 13, data processing unit 20 for processing data obtained by mass spectrometer 13, control unit 30 for performing overall control of the entire system including analysis, and analysis An input unit 33 for the user to set conditions and the like, and a display unit 34 for displaying the analysis progress status, analysis results, and the like are provided.

Usually, the mobile phases A1 to A4 and the mobile phases B1 to B4 are different types of mobile phase solvents. The six types of columns 11 are also columns having different separation characteristics. For example, to extract a target compound from a mixed solution or natural extract after synthesis reaction for the purpose of drug discovery, the identity of the sample used for analysis is somewhat clear, and the target compound is also limited to some extent . Therefore, the type of mobile phase and column to be used can be narrowed to some extent from such prior knowledge and knowledge, and the analyst may prepare an appropriate mobile phase and column in advance.

The mass spectrometer 13 is a quadrupole mass spectrometer equipped with, for example, an electrospray ion source or an atmospheric pressure chemical ion source, and repeats scan measurement within a predetermined mass-to-charge ratio range, so that a predetermined charge is obtained for each scan measurement. Mass spectral data over a specific range can be obtained. The data processing unit 20 includes a data storage unit 21, a chromatogram creation unit 22, and a target peak extraction unit 23 as functional blocks. The control unit 30 includes a separation condition search schedule creation unit 31 and a separation condition search control unit 32 as functional blocks. In general, the data processing unit 20 and the control unit 30 (in some cases, a part of the analysis control unit 14) use a personal computer as a hardware resource, and execute dedicated control / processing software installed in the personal computer. Thus, the functions as the data processing unit 20 and the control unit 30 can be exhibited.

Next, a characteristic separation condition search operation in the LC / MS of the present embodiment will be described in detail. FIG. 2 is a flowchart showing the control and processing of the separation condition search operation, FIG. 3 is a diagram showing an example of a display screen when setting an analysis reservation, FIG. 4 is a diagram showing an example of a created analysis schedule, and FIG. FIG. 6 is a diagram illustrating an example of a display screen being executed, FIG. 6 is a diagram illustrating an example of a part of the display screen when an additional analysis reservation is set, and FIG. 7 is a diagram illustrating an example of an analysis schedule after adjusting the schedule for the additional analysis reservation, FIG. 8 is a diagram showing an example of the analysis report display screen after the analysis is completed.

When a certain analyst wants to examine the optimum separation condition for separating the target compound contained in a plurality of samples at hand, the input unit 33 performs a predetermined operation. In response to this operation, the separation condition search schedule creation unit 31 displays an analysis reservation acceptance screen 50 as shown in FIG. 3 for accepting an analysis reservation on the screen of the display unit 34. In the analysis reservation reception screen 50, the analyst inputs and sets the number of samples, the mass-to-charge ratio m / z characterizing the target compound in each sample, and the like (step S1). As shown in FIG. 3, a sample position indication image 51 showing the positions of a plurality of samples accommodated in the sample rack is drawn on the analysis reservation reception screen 50, and the analyst can display the sample position indicated on the image 51. Put the sample on. In the example of FIG. 3, m / z = 250 and 300 are set as the mass-to-charge ratio characterizing the target compound, respectively, for the two samples.

In the LC / MS of this embodiment, not an individual analyst, but a system administrator sets in advance an analytical method describing the LC analysis conditions such as the type of column to be used, the type of mobile phase, and the gradient conditions. The LC analysis is automatically executed according to all the set analysis methods. Therefore, here, the analyst does not need to set the above-described analysis conditions again, but the analyst may be able to set such analysis conditions.

When the information necessary for the analysis is input, the separation condition search schedule creation unit 31 reduces the number of executions of washing and equilibration of the flow path including the column as much as possible every time the column and the mobile phase are switched. Next, the analysis order is rearranged. Specifically, as shown in FIG. 4, the analysis is continuously performed in which the combination of the column type and the mobile phase type, which are separation conditions, is the same, and washing (and equilibration is performed when the column or the mobile phase is switched). An analysis schedule is created by rearranging the analysis order so as to execute (Step S2). In FIG. 4, a combination of one column and two mobile phases (for example, column 1 / mobile phase A1, B1) is an analysis condition included in one analysis method.

Then, the analysis schedule created as described above is transferred to the separation condition search control unit 32, and the separation condition search control unit 32 controls each unit via the analysis control unit 14 so as to execute the analysis according to the analysis schedule. (Step S3).

For example, in the analysis of the first row of the analysis schedule shown in FIG. 4 (sample 1 column 1 / mobile phase A1, B1), the second switching valve moves so that the first switching valve 3 selects the mobile phase A1. It is switched so that phase B1 is selected. Further, the third and

fourth switching valves

10 and 12 are switched so that the uppermost column 11a is selected. In this state, the first liquid feed pump 5 feeds the mobile phase A1 at a predetermined flow rate, and the second liquid feed pump 6 feeds the mobile phase B1 at a predetermined flow rate. Both mobile phases are mixed by the mixer 7 and sent to the column 11a through the injector 8 and the third switching valve 10. The mixing ratio of the mobile phases A1 and B1 is based on the gradient conditions included in the same analytical method.

The autosampler 9 sucks the sample placed at the designated position on the sample rack and supplies it to the injector 8, and the injector 8 injects the sample into the mobile phase at a predetermined timing. The injected sample rides on the flow of the mobile phase and is sent to the column 11a. In the process of passing through the column 11a, the contained compounds are separated and eluted in the time direction. The eluate is introduced into the mass spectrometer 13 through the fourth switching valve 12. When the amount of liquid that can be introduced into the mass spectrometer 13 is limited, a part of the eluate divided through a splitter or the like may be introduced into the mass spectrometer 13. The mass spectrometer 13 ionizes the compound contained in the introduced eluate and repeatedly acquires mass spectrum data for the generated ions. The mass spectrum data is sent to the data processing unit 20 and sequentially stored in the data storage unit 21.

The separation condition search control unit 32 determines whether or not there is an instruction for additional analysis reservation after the start of analysis execution (step S4). This will be described later. If there is no instruction for additional analysis reservation, it is next determined whether or not one analysis has been completed (step S6), and if not yet completed, the process returns to step S3. Therefore, if there is no instruction for additional analysis reservation, the process of steps S3 → S4 → S6 is repeated until one LC / MS analysis corresponding to one line on the analysis schedule shown in FIG. 4 is completed. When it is determined that one LC / MS analysis has been completed due to the end of the predetermined analysis time defined in the analysis method, the separation condition search control unit 32 has completed all the analyzes set in the analysis schedule. (Step S7), and if the entire analysis is not completed, the process proceeds to the next analysis on the analysis schedule.

When shifting to the next analysis, it is determined whether or not sample exchange is necessary by checking the sample ID and the like on the analysis schedule (step S8). If the sample IDs of the analysis executed immediately before and the analysis to be executed next are different, it is determined that the sample needs to be exchanged, and the autosampler 9 is controlled so as to prepare the designated next sample (step S9). For example, when shifting from the first line to the second line analysis on the analysis schedule shown in FIG. 4, it is necessary to replace the sample, so the process of step S <b> 9 is executed.

Next, the separation condition search control unit 32 determines whether or not it is necessary to change at least one of the separation conditions, specifically, the mobile phase or the column (step S10), and if it is necessary to change at least one of them. The switching

valves

3, 4, 10, and 12 are controlled so that the designated next mobile phase and / or column is connected (step S11). Then, the process returns to step S3, and the next analysis in which at least one of the sample and the separation condition is changed is performed. During the execution of such an analysis, an analysis execution screen 60 as shown in FIG. 5 is displayed on the screen of the display unit 34. On the analysis execution screen 60, a table 61 indicating how far each analysis according to the analysis schedule has been completed and which analysis is being executed, and a sample position indication indicating the position of the sample for which analysis has been completed An image 62 is displayed.

This LC / MS is supposed to be used by a plurality of analysts. Therefore, even when an analysis designated by a certain analyst is being performed, another (or the same as above) is used. It is possible for an analyst to register a sample to be analyzed. That is, if an analyst performs the same operation as step S1 by the input unit 33 during the analysis execution, the analysis reservation acceptance screen 50 is displayed on the screen of the display unit 34, and a new number of samples can be designated. It becomes. However, some samples are already placed on the sample rack, and no additional samples can be placed at that position. Therefore, the separation condition search schedule creation unit 31 automatically determines a position where an additional sample can be placed, and presents the sample position on the sample position instruction image 51 drawn on the analysis reservation reception screen 50. The analyst places a sample at the presented position (step S1A).

As described above, when a certain analyst makes an analysis reservation for a new sample during the execution of the analysis (Yes in step S4), the separation condition search schedule creation unit 31 determines that point in the already created analysis schedule. The analysis schedule is adjusted so that the number of washings is reduced as much as possible by combining the analysis that has not been performed in step 1 and the analysis on the newly added sample (step S5). Specifically, for example, an analysis reservation for a new sample (sample 3) was made during the execution of the analysis in the fourth row (sample 1 column 1 / mobile phase A1, B2) in the analysis schedule shown in FIG. Then, as shown in FIG. 7, the analysis for the new sample is inserted on the analysis schedule. Thus, when an analysis reservation for a new sample is made during the execution of the analysis, the analysis order is dynamically optimized so that the number of washings is not increased as much as possible.

Thus, the analysis is executed under different separation conditions for each of the plurality of samples according to the analysis schedule created first or appropriately adjusted in the middle, and when all the analyzes are completed, the process proceeds from step S7 to S12. In the data processing unit 20, the chromatogram creation unit 22 creates a total ion chromatogram for each sample and for each separation condition based on the mass spectrum data for each analysis stored in the data storage unit 21 (step S12).

The target peak extraction unit 23 creates a mass spectrum for each scan based on the mass spectrum data collected for each sample and for each separation condition, and the mass-to-charge ratio mass set for the sample in step S1. Obtain the signal intensity of the spectral peak. For example, in the case of sample 1, the signal intensity of the mass spectrum peak of m / z = 250 is obtained. Then, it is determined whether the signal intensity of the mass spectrum peak is equal to or higher than a predetermined threshold, a mass spectrum having a mass spectrum peak with a signal intensity equal to or higher than the threshold is specified, and further, at the time when the mass spectrum appears. A corresponding chromatogram peak is specified (step S13). By appropriately setting the threshold value, a chromatogram peak that is highly likely to be derived from the target compound can be identified.

The threshold for determining the mass spectrum peak signal intensity may be determined in advance by the manufacturer of the device, or may be set freely by the user (analyzer or system administrator). Good. Further, the threshold value is not an absolute value, and may be a relative value with respect to the signal intensity of another peak, for example.

When the analyst issues an analysis result report display instruction via the input unit 33, the control unit 30, as shown in FIG. 8, for example, selects a plurality of chromatograms under different separation conditions for a specified sample ( Total ion chromatograms) are displayed side by side on the screen of the display unit 34. At this time, the chromatogram peaks identified in step S13 are colored (indicated by hatching in FIG. 8) so that they can be easily distinguished from other peaks (step S14). As a result, the analyst can confirm the chromatogram of the same sample under different separation conditions at a glance, and also immediately understand the peak of the target compound to be separated. Appropriate separation conditions can be known immediately. Of course, such report results can be displayed as well as output from a printer (not shown).

Further, instead of displaying a plurality of chromatograms side by side as shown in FIG. 8, the display format can be changed as appropriate, for example, the horizontal axis and the vertical axis are aligned and displayed in the same graph frame. Also, the display format of the specified chromatogram peak is not limited to the coloring display of the peak area, but can be changed as appropriate, such as displaying the peak curve in color or displaying a translucent display other than the specific chromatogram peak. it can.

Further, in the above embodiment, when the analyst makes an analysis reservation in steps S1 and S1A, the position where the sample should be placed is presented on the sample position indicating image 51, and the analyst places the sample at that position. Alternatively, the analyst may be allowed to specify the position where the sample is placed.

For example, when the analyst performs a predetermined operation on the input unit 33, the separation condition search schedule creation unit 31 places an additional sample on the sample position indication image 51 in the analysis reservation reception screen 50 as shown in FIG. Indicates possible positions. In this example, a position indicated by a solid line is a position where a sample can be placed, and a position indicated by a dotted line is a position where a sample cannot be placed (that is, a reserved position). On the image 51, the analyst designates a position where the sample is to be placed by clicking on an arbitrary position among a plurality of positions where the sample can be placed. Then, the sample may be actually placed at the position designated by itself. However, if there is a discrepancy between the position specified by the analyst and the location where the sample is actually placed, it will hinder the operation. For example, if there is such a discrepancy, it is better to notify the analyst of warning by displaying an error. .

Further, the above embodiment is merely an example of the present invention, and can be appropriately modified, modified, and added within the scope of the gist of the present invention. For example, in the above embodiments, the present invention is applied to LC / MS, but the present invention is also applicable to GC / MS. Further, when a mass spectrometer is not used as a detector, the processing shown in step S13 and display based on the processing result cannot be performed, but other functions can be realized.

DESCRIPTION OF SYMBOLS 1 ... Mobile phase container 2 ... Cleaning

liquid container

3, 4, 10, 12 ...

Switching valve

5, 6 ... Feed pump 7 ... Mixer 8 ... Injector 9 ... Autosampler 11 (11a-11f) ... Column 13 ... Atmospheric pressure ionization Mass spectrometer 14 ... analysis control unit 20 ... data processing unit 21 ... data storage unit 22 ... chromatogram creation unit 23 ... target peak extraction unit 30 ... control unit 31 ... separation condition search schedule creation unit 32 ... separation condition search control unit 33 ... Input unit 34 ... Display unit

Claims

A column for separating compounds contained in a sample in a time direction, a mobile phase supply unit that supplies a mobile phase to the column, and a sample is introduced into the mobile phase supplied to the column by the mobile phase supply unit In a chromatographic analyzer comprising: a sample introduction unit; and a detection unit that detects each compound in the sample eluted from the column,
a) a separation condition switching unit that sequentially switches the separation conditions among a plurality of separation conditions prepared in advance for one or more separation elements that affect the separation state of the target compound;
b) an analysis control unit that repeatedly introduces the same sample by the sample introduction unit while switching the separation condition by the separation condition switching unit, and performs chromatographic analysis of the same sample under each separation condition;
c) Chromatography for preparing chromatograms under different separation conditions based on data obtained by the detection unit in a plurality of chromatographic analyzes on the same sample performed under the control of the analysis control unit. Gram creation part,
A chromatographic analyzer characterized in that a plurality of chromatograms created by the chromatogram creation unit can be used to search for separation conditions suitable for a target compound in a sample.
The chromatographic analyzer according to claim 1,
An input unit for the user to specify a plurality of samples to be analyzed in series;
When a plurality of samples to be analyzed in series are specified through the input unit, the sample and the separation conditions are combined so that chromatographic analysis is continuously performed on the plurality of samples under the same separation conditions. A schedule creation unit for creating an analysis schedule;
The chromatographic analysis apparatus, wherein the analysis control unit performs a chromatographic analysis according to an analysis schedule created by the schedule creation unit.
The chromatographic analyzer according to claim 2,
The input unit allows additional designation of one or more samples by the user even during chromatographic analysis execution,
When the input of the sample to be analyzed is instructed by the input unit, the schedule creation unit, for the sample that has not been analyzed and the sample that has been additionally instructed in the analysis schedule being executed, under the same separation condition Re-adjust the combination of sample and separation conditions to correct the analysis schedule so that chromatographic analysis on multiple samples is performed continuously,
The chromatographic analyzer, wherein the analysis control unit continues the chromatographic analysis according to the analysis schedule modified by the schedule creation unit.
A chromatographic analyzer according to claim 2 or 3,
The detection unit is a mass spectrometer that repeatedly acquires mass spectrum data,
The input unit can set the molecular weight of the target compound or the mass-to-charge ratio characterizing the compound for each sample,
A peak extraction unit for identifying a chromatogram peak including a significant mass spectrum peak corresponding to the molecular weight or mass-to-charge ratio set in the input unit based on the mass spectrum data obtained by the mass spectrometer; A chromatographic analyzer characterized by that.
The chromatographic analyzer according to claim 4,
The chromatogram creation unit displays a created chromatogram on a display screen in a manner in which the chromatogram peak identified by the peak extraction unit and other chromatogram peaks can be visually identified. A chromatographic analyzer comprising:
A chromatographic analyzer according to any one of claims 1 to 5,
The chromatogram analyzer includes a drawing processing unit that displays a plurality of chromatograms obtained under different separation conditions for one sample side by side or superimposed on a display screen.
A chromatographic analyzer according to claim 2 or 3,
A sample selection unit that selects a specified sample from a plurality of samples stored in a rack and supplies the sample to the sample introduction unit;
A chromatographic analysis characterized in that when a user designates or adds a sample, a display that can visually identify a sample storage position that can be used in the rack and a sample storage position that cannot be used on the rack is displayed on the display screen. apparatus.
The chromatographic analyzer according to any one of claims 1 to 7,
One of the separation elements is the column, the column is different from the plurality of separation conditions, and the separation condition switching unit is a column switching unit that switches a column used for chromatographic analysis. A characteristic chromatograph analyzer.
A chromatographic analyzer according to any one of claims 1 to 8,
One of the separation elements is a mobile phase, which is a mobile phase of a different type from the plurality of separation conditions, and the separation condition switching unit is in the mobile phase supply unit and is supplied to the column. A chromatographic analyzer characterized by being a flow path switching unit for switching between.
A chromatographic analyzer according to any one of claims 1 to 8,
One of the separation elements is a mobile phase, and a plurality of gradient conditions in which a change in a mixing ratio and a temporal mixing ratio are different when mixing a plurality of mobile phases of different types from the plurality of separation conditions. The separation condition switching unit is a pump control unit that changes the flow rate by controlling the operation of a liquid feed pump that feeds a plurality of mixed mobile phases in the mobile phase supply unit. A chromatographic analyzer characterized by that.