JP2001208738A - Analysis condition selection method and high performance liquid chromatography device - Google Patents

Abstract

(57) [Summary] [Problem] To analyze a compound by reducing the time required to select the optimal combination of a column and a carrier solution for the analysis of an analyte when performing compound analysis by high performance liquid chromatography. An analysis condition selection method capable of reducing the total time is provided. SOLUTION: A plurality of types of analysis solutions obtained by injecting a sample solution containing an analyte into a carrier solution sent from a liquid sending unit 1 from a sample injection unit 2 as a stationary phase in a separation unit 3 are set in advance. Are sequentially supplied to the columns A to F, and the obtained separation solution is analyzed in the detection unit 4, and based on the analysis result, analysis conditions suitable for the analyte are selected.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

The present invention relates to a high performance liquid chromatography used as an analysis means of an organic synthesis reaction, and to an analysis condition (optimal of a stationary phase and a mobile phase) for a compound (target compound) to be analyzed. And a high-performance liquid chromatography apparatus.

[0002]

2. Description of the Related Art Conventionally, liquid chromatography has been widely used as an analysis means of an organic synthesis reaction.
Among them, high-performance liquid chromatography is suitably used as the above-mentioned analysis means, because a small amount of sample can be analyzed quickly, easily, with high accuracy and high reproducibility.

In general, in an analysis using high performance liquid chromatography, an organic compound to be analyzed (hereinafter, referred to as an organic compound) is used.
The column (stationary phase) used differs depending on the analyte. In particular, a chiral column (column for analyzing an optically active compound) has a different optimum column depending on the analyte, and therefore, for more accurate analysis, it is necessary to select a column according to the analyte.

In order to correctly analyze an object to be analyzed,
It is necessary to select not only the column but also the carrier solution (mobile phase) flowing through the column according to the analyte.

As described above, in high performance liquid chromatography, it is necessary to select optimal analysis conditions according to an analyte.

Conventionally, the selection of analysis conditions (column and carrier solution) in high performance liquid chromatography is as follows:
It was done as follows.

[0007] First, several candidate columns and several carrier solutions are selected for an analyte, and each candidate column and a container containing the carrier solution are sequentially attached to a high-performance liquid chromatography apparatus, and the candidate columns are selected. And the suitability of the carrier solution was determined.

[0008] After the optimum column and carrier solution for the analysis of the object to be analyzed are selected from the candidate column and the carrier solution in this way, the compounds are further analyzed using these columns and the carrier solution.

In this case, in order to analyze a plurality of types of analytes, it is necessary to use a column and a carrier solution selected for each analyte. Therefore, the column and the carrier solution are replaced for each analyte. And it took time to analyze.

[0010] Therefore, for example, a column switching system for high-performance liquid chromatography disclosed in Japanese Patent Application Laid-Open No. 242151/1990 is disclosed in Japanese Patent Application Laid-Open No. HEI 2-242151. A technique of selecting a column (one column or a combination of a plurality of columns) only by switching a valve is disclosed.

According to the technique disclosed in the above publication, since a plurality of columns are set in advance, the analysis time for analyzing a plurality of types of analytes can be reduced.

[0012]

However, the following problems arise in the above-described conventional analysis condition selection method and the technology disclosed in the above publication.

(1) In the conventional analysis condition selection method, the replacement of the candidate column and the carrier solution is performed manually by an analyst or the like, and until the column and the carrier solution optimal for the analysis of the analyte are selected. Requires a great deal of time, and as a result, the time required for the analysis is extremely long, and the total time required for the analysis is prolonged.

(2) In the technique disclosed in the above publication, in order to stabilize the inside of the system, each column is connected in series and the carrier solution flows through the column. When the mobile phase needs to be replaced depending on the target, that is, when the carrier solution needs to be replaced, the carrier solution needs to be replaced, and furthermore, it takes a lot of time to stabilize the system with the replaced carrier solution. .

Therefore, according to the technique disclosed in the above publication, it takes a very long time to analyze a plurality of types of analytes having different combinations of columns and carriers, and the total time required for the analysis becomes longer. Problems arise.

The present invention has been made in order to solve the above problems.
When analyzing compounds by high performance liquid chromatography, select analysis conditions that can reduce the total time required for compound analysis by reducing the time required to select the optimal combination of column and carrier solution for the analyte analysis In addition to providing a method, even for multiple types of analytes in which the combination of the column and the carrier solution is different, the total time required for compound analysis can be reduced by shortening the time required for column replacement and carrier solution replacement. It is an object of the present invention to provide a high-performance liquid chromatography device capable of reducing time.

[0017]

According to a first aspect of the present invention, there is provided an analysis condition selection method for selecting an analysis condition suitable for an analyte to be analyzed by a high performance liquid chromatography apparatus. In the method, an analysis solution obtained by mixing a sample solution containing an analyte in a carrier solution as a mobile phase was sequentially supplied to a plurality of types of columns previously set as a stationary phase, and the obtained separation solution was analyzed. The method is characterized in that an analysis condition suitable for the analysis target is selected based on the result.

According to the above arrangement, the analysis solution is sequentially supplied to a plurality of types of stationary phases set in advance, and based on the obtained analysis results, analysis conditions suitable for the analyte, that is, stationary phase and mobile phase. Since the phase is selected, it is not necessary to manually replace the column as the stationary phase or the carrier solution as the mobile phase as in the related art, and the time required for selecting the column and the carrier solution can be greatly reduced.

According to a second aspect of the present invention, in order to solve the above-mentioned problem, in addition to the constitution of the first aspect, after the supply of the analysis solution to all the columns is completed, another type of the carrier solution is used. And perform the analysis again.

According to the above configuration, after the analysis solution is sent to all the columns, the carrier solution is switched and sent out, so that the analyte to be analyzed using the same carrier solution is switched by switching only the columns. It can be analyzed continuously.

Accordingly, when the analytes using different carrier solutions are screened in the same apparatus, the screening can be performed for each analyte measurable with the same carrier solution. Can be efficiently selected.

According to a third aspect of the present invention, in order to solve the above-mentioned problem, in addition to the constitution of the first or second aspect, the separation solution obtained in the column is analyzed by a plurality of detection methods. It is characterized by doing.

According to the above configuration, since the separated solution is analyzed by a plurality of types of detection methods, it is possible to determine from the plurality of analysis results whether or not the analysis conditions are suitable for the analyte. The reliability of the correctness of the selection of the analysis conditions such as the column and the carrier solution can be improved.
For example, when the analyte is an optically active compound, the optically active compound is easily detected by using an optical rotation detector (OR) together with an ultraviolet detector (UV), which is a general detector, as an analysis means. be able to.

According to a fourth aspect of the present invention, there is provided a high-performance liquid chromatography apparatus, comprising: a separating section comprising a plurality of types of columns as a stationary phase; a liquid sending section for sending a carrier solution as a mobile phase; An analysis solution obtained by mixing a sample solution containing the analyte in the carrier solution sent from the liquid sending unit; andan analyzing means for analyzing the separated solution obtained by supplying the solution to each column of the separation unit. It is characterized by having.

According to the above configuration, a plurality of types of analytes are analyzed by preparing types that can be set according to the analytes for the column as the stationary phase and the carrier solution as the mobile phase. In this case, it is possible to eliminate the need to replace the column and the carrier solution, and as a result, it is possible to greatly reduce the total time required for the analysis.

According to a fifth aspect of the present invention, in order to solve the above-mentioned problem, in addition to the structure of the fourth aspect, the liquid sending section includes a switching sending means for switching and sending a plurality of types of carrier solutions. Is provided, and the switching and sending means switches the carrier solution to be sent after the analysis solution has been sent to all of the columns.

According to the above configuration, after the analysis solution is sent out to all the columns in the stationary phase by the switching and sending means, the carrier solution is switched and sent out, so that the analysis can be performed using the same carrier solution. The analyte to be analyzed can be continuously analyzed by switching only the column.

Accordingly, when the analytes using different carrier solutions are analyzed by the same high-performance liquid chromatography apparatus, the analysis can be performed for each analyte measurable with the same carrier solution. An object can be efficiently analyzed.

According to a sixth aspect of the present invention, in order to solve the above-mentioned problems, in addition to the constitution of the fourth or fifth aspect, the analyzing means further comprises an analyzing object contained in the separation solution obtained from the column. It is characterized by comprising a plurality of types of detectors for detecting objects.

According to the above configuration, the object to be analyzed can be determined from the detection results of the plurality of detectors, so that the detection accuracy of the object to be analyzed can be improved. Moreover, by combining the detectors, the analyte can be analyzed efficiently. For example, when the analyte is an optically active compound, an ultraviolet detector (U
By using an optical rotation detector (OR) with V)
An optically active compound can be easily detected.

According to a seventh aspect of the present invention, there is provided a high-performance liquid chromatography apparatus, wherein each of the columns is connected in parallel in addition to any one of the fourth to sixth aspects. And

According to the above arrangement, when the inside of the high-performance liquid chromatography system is brought into a steady state by connecting the columns in parallel, the carrier solution sent from the sending section is simultaneously supplied to each column. And can be sent to the analysis means at the same time. As a result, the time required for stabilization in the high-performance liquid chromatography system can be significantly reduced, and as a result, the total time required for detecting the analyte can be significantly reduced.

[0033]

DESCRIPTION OF THE PREFERRED EMBODIMENTS One embodiment of the present invention will be described.
The following is a description based on FIGS. 1 to 5.

As shown in FIG. 1, the high performance liquid chromatography apparatus according to the present embodiment includes a liquid sending section 1, a sample injection section 2, a separation section 3, a detection section 4, and a control section 5.

The liquid sending section 1 includes a valve 11 and a mixer 1
2. The pump 13 is configured to be connected in series,
The carrier solution (solutions A to D) contained in the mobile phase reservoir 14
The liquid is switched by the valve 11 and sent to the separation unit 3 through the mixer 12 and the pump 13. That is, the carrier solution from the mobile phase reservoir 14
After being supplied into the mixer 12 by the pump 13, it is stirred and sent to the separation unit 3.

The valve 11 is a multiway branch valve having four input side valves and one output side valve, and can selectively open and close the carrier solution input side valve. I have. That is, the valve 11 opens and closes only one valve to send one type of carrier solution to the mixer 12, or opens and closes a plurality of valves to send out many types of carrier solution to the mixer 12. be able to.

The switching control of the valve 11 is performed based on a control signal C1 output from the control unit 5.

The carrier solution is subjected to a degassing process before flowing into the mixer 12 so as to prevent bubbles from being generated in the flow path in the high performance liquid chromatography apparatus.

The carrier solution contained in the mobile phase storage 14 is appropriately selected according to the organic compound to be analyzed (hereinafter, referred to as the analyte), similarly to the column of the separation unit 3 described later. Things.

A sample injecting section 2 for injecting a sample solution containing an analyte is provided between the liquid sending section 1 and the separating section 3.
Is provided. Thus, the sample liquid is sent to the separation unit 3 together with the carrier solution sent from the liquid sending unit 1.

The method of injecting the sample liquid into the sample injecting section 2 includes a syringe method, a valve leaping method, a universal valve method, and the like.

The sample liquid injection in the sample injection section 2 is performed based on a control signal C2 output from the control section 5.

The separation section 3 is provided with six columns A to F for component separation as a stationary phase, and a mixed solution composed of a carrier solution and a sample solution before analysis (hereinafter referred to as an analysis solution). For selectively supplying to the columns A to F, and analysis after analysis from a solution in which each component contained in the analysis solution is separated by the columns A to F (hereinafter, referred to as a separated solution). A valve 32 for selectively discharging the solution is provided.

The opening and closing of the valves 31 and 32 is controlled based on control signals C3 and C4 output from the control unit 5.

The liquid flowing into the separation unit 3 may be only the carrier solution in addition to the analysis solution as described above. Unless otherwise specified, the liquid will be simply referred to as the liquid. The separation solution flowing out of the separation unit 3 is also described as a liquid unless otherwise specified.

The columns A to F are connected in parallel, and each column can perform component separation independently.

The valve 31 is a multi-way branch valve having one input-side valve and six output-side valves. The valve 32 has six input-side valves and one output-side valve. There are two multi-way branch valves.

That is, the liquid from the liquid sending section 1 flows into one valve on the input side of the valve 31, while columns A to F are connected to the six valves on the output side, respectively. The liquid from the liquid sending section 1 is sent to the columns A to F through the liquid supply section.

The valve 31 selectively opens the output side valve, and sends out the liquid flowing from the input side valve to the column connected to the selected valve. Further, the valve 31 can also open all valves on the output side and send out the liquid flowing from the valves on the input side to all the columns A to F. Since the liquid can be simultaneously sent to all the columns A to F, the columns A to F can be simultaneously brought into a steady state by the carrier solution.

On the other hand, the valve 32 provided on the output side of the separation section 3 has the same function as the above-mentioned valve 31, and the liquid inflow direction is reversed. That is, 6 on the input side
The columns A to F are connected to one valve, and the one valve on the output side is connected to the valve 41 in the detection unit 4 at the next stage. In the valve 32, the input side valve can be selectively opened, or all valves can be opened.

Therefore, the above-described valve 31 and valve 3
By controlling the opening and closing of the valves in 2 in conjunction with each other, it is possible to flow the liquid only to the target column or to flow the liquid to all the columns. For example, when all the valves on the output side of the valve 31 are opened, the valves may be controlled so that all the valves on the input side of the valve 32 are opened. When the liquid is allowed to flow through only one column, the valve 31 opens the output side valve connected to the target column, while the valve 3
In 2, the control may be performed such that the input side valve connected to the column is opened.

The details of the opening / closing control of the valves 31 and 32 will be described later.

The columns A to F used in the separation section 3
Is a candidate column selected according to the sample liquid to be injected in the sample injection unit 2, that is, the analyte. Further, in the above-described separation unit 3, an example in which six columns are used has been described. However, the present invention is not limited to this, and can be appropriately changed according to an analyte.

A detector 4 for analyzing the separated solution from which the components have been separated by the separator 3 is provided next to the separator 3.
Is provided.

The detection section 4 is provided with a valve 41 on the liquid inflow side from the separation section 3, and different types of detectors A to C are connected to the liquid outflow side of the valve 41. I have. These detectors are connected to the valve 41 in the order of A, B, C, and A. One detector A is further connected with detectors B and C in series.

The valve 41 is a multi-way branch valve provided with one valve on the input side and four valves on the output side. Opening / closing control of each valve is performed based on a control signal C5 from the control unit 5.

One of the valves on the input side of the valve 41 is connected to the flow path through which the liquid delivered from the output side of the valve 32 of the separation unit 3 flows, while the four valves on the output side are connected to the four valves on the output side. , Detectors A to C of the detection unit 4 are connected.

That is, in the detection unit 4, after the liquid from the separation unit 3 is input to the input side valve of the valve 41, the output side valve of the valve 41 is selectively opened, and the detectors A to A The liquid is delivered to at least one of C.

Examples of the detectors A to C include an ultraviolet absorption detector (UV), a differential refraction detector (RI), and an optical rotation detector (OR). In FIG. 1, if the detector A is UV, the detector B is OR, and the detector C is RI, the respective detectors may be used separately, or the detector A consisting of UV may be OR, RI May be connected in series.

Therefore, in this embodiment, the detector A
To C can be used together, and the reliability of the analysis result can be improved. For example, when the analyte is a chiral compound, it is necessary to determine whether a separation peak obtained by analyzing with UV or RI is a chiral compound or not.
Use OR.

The detection signals obtained by the detectors A to C of the detection section 4 are output to the control section 5 as an electric signal D1.

The control section 5 generates the above-described control signals C1 to C5 based on the detection signals from the detection section 4 and applies the control signals C1 to C5 to the valve 11, the sample injection section 2, and the valve 31. , The valve 32, and the valve 41.

Generally, in a high performance liquid chromatography apparatus, it is necessary to appropriately select a column as a stationary phase and a carrier solution as a mobile phase in order to correctly analyze an analyte.

In the high-performance liquid chromatography apparatus having the above-described configuration, the opening and closing of the valve 11, the sample injection unit 2, the valve 31, the valve 32, and the valve 41 are controlled by the control signals C1 to C5 from the control unit 5, so that the liquid is sent. In the section 1, the plurality of types of carrier solutions are sequentially switched to separate sections 3.
At the same time, and an analysis solution containing an analyte can be caused to flow by sequentially switching a plurality of types of columns in the separation unit 3.

In this case, first, a carrier solution is set,
The detection solution is obtained by flowing the sample solution together with the carrier solution to the six columns A to F, which are the candidate columns, in order, and then switching the carrier solution to the six columns A to F in the same manner. The detection liquid is obtained by flowing the sample liquid together with the carrier solution. In this way, until the type of the carrier solution reaches the prescribed number, the carrier solution is sequentially switched,
The detection data is obtained by flowing the sample solution together with the carrier solution in order to the columns A to F, which are the candidate columns.

Here, the above-mentioned candidate column is a column which is considered to be optimal for an object to be analyzed based on past analysis data and the like, and the type differs depending on the object to be analyzed.

As described above, by switching the columns A to F in order and comparing the detection data obtained by switching the carrier solution in order, the optimum column and carrier solution for the analyte can be determined. Can be easily and quickly found.

That is, in the high-performance liquid chromatography apparatus having the above-described configuration, it is possible to realize an analysis condition selection method for selecting a combination of a column and a carrier solution that is optimal for an analyte as an analysis condition.

Here, the flow of the analysis condition selection processing by the analysis condition selection method using the high-performance liquid chromatography apparatus having the above configuration will be described below with reference to the flowcharts shown in FIGS. Note that the analysis condition selection processing is performed based on a control program stored in the control unit 5. In the analysis condition selection processing, selecting an optimal column and carrier solution for an analyte is, in other words, performing a process (screening) of sieving a plurality of columns and a carrier solution.

First, in the preparation stage, an analysis sample target (analysis target) to be analyzed is determined, and a sample liquid for measurement is prepared.

Next, according to the analysis target, n (n
.., N) candidate columns are selected and set at predetermined positions of the separation unit 3 (step S1). Here, since the number of columns used in the separation unit 3 is six, N = 6.

Next, according to the analysis target, m (m = m
1, 2, 3, ..., M) types of mobile phases
(Step S2). Here, the mobile phase is a carrier solution, and M = 4 because there are four types of carrier solutions (solutions A to D) used in the liquid sending unit 1.

In the above carrier solution, when it is necessary to adjust the pH or when a buffer solution is used, the carrier solution is adjusted and then set in the liquid sending section 1.

Subsequently, measurement conditions are set (step S).
3). Here, for the WS (workstation) constituting the control unit 5, the type of column and the measurement order, the type of carrier solution (solvent type, composition, etc.), the measurement order, the detector and the detector are used. The input of the measurement wavelength is performed.

That is, in step S3, it is set from which column the analysis solution is to flow and from which carrier solution to use.

Therefore, in consideration of the stabilization in the high performance liquid chromatography system, it is preferable to screen the target column once and then switch the mobile phase to further continue the column screening.

The above measurement conditions can be arbitrarily determined by the analyst based on experience, past data, etc., for example, past screening data (compound structure, most suitable column, mobile phase, wavelength, etc.) Can be stored in the control unit 5 and automatically set so that the measurement is performed in order from the column having the highest hit ratio in the past (the probability of being regarded as the optimal column for the analysis target). It is also possible to input a part or all of the structure of the compound to be analyzed and set to preferentially measure a column having a high hit ratio for a compound having a similar structure.

Here, the hit ratio of the column is represented by (the number of compounds determined to be separable) / (the total number of compounds). The number of compounds determined to be separable indicates the number of compounds determined to be separable among compounds previously analyzed by the present method (apparatus) and other methods using a certain column, and the total number of compounds is And the total number of compounds analyzed in the past by the method (apparatus) of the present application and other techniques. The hit rate may include not only the result of the actual analysis but also information described in a known document such as a catalog of a column maker or the like.

When the analysis target is an optically active compound, if an ultraviolet absorption detector (UV) and an optical rotation detector (OR) which are general detectors are connected in series, It is preferable because the peak can be easily determined to be an optically active substance.

Prior to the measurement, the conditions for stabilizing the inside of the high-performance liquid chromatography system used in the analysis condition selection method so that reliable data can be obtained are input to the control unit 5.

The conditions input here are, for example, to stabilize all the columns to be screened in a short time and to open all the branch valves (valves 31 and 32) to which the columns to be screened are connected. The control unit 5 receives the setting conditions and the electric signal D1 from the detector, and when the fluctuation rate of the electric signal D1 for a certain period of time falls below a certain value, the inside of the high-performance liquid chromatography system becomes a steady state. There is a condition for judging that the time has passed and making the screening startable.

When the setting of the measurement conditions is completed, the stabilization processing of the high performance liquid chromatography apparatus is performed (step S4). Details of the device stabilization process will be described later.

In step S4, after the inside of the high-performance liquid chromatography system has reached a steady state, a screening process is performed (step S5). The details of this screening process will be described later.

Subsequently, it is determined whether or not m = M (step S6). Here, since M = 4 types of carrier solutions, it is determined whether or not the screening process of the 4 types of carrier solutions has been completed.

In step S6, if it is determined that m = M, that is, that the screening process for the four types of carrier solutions has been completed, the analysis condition selection process using the high performance liquid chromatography apparatus is completed.

On the other hand, if it is determined in step S6 that m ≠ M, that is, that the screening process for the four types of carrier solutions has not been completed, the flow is switched to the next carrier solution (step S7), and the process proceeds to step S4. Then, the device stabilization process and the screening process are performed again.

As described above, when the analysis condition selection processing is completed, the data obtained by the screening processing
Determine which column and which carrier solution are most suitable for the analysis target. For example, as the data, the shape of each peak in the obtained chart, the separation state of each peak, the time required for analysis, and the like are comprehensively determined, and the most suitable column and carrier solution are selected. This decision
Performed by the analyst.

When the analysis target is an optically active compound, as described above, an optical rotation detector (OR)
The determination can be made easier and quicker by using.

Here, the flow of the apparatus stabilization processing for bringing the inside of the high-performance liquid chromatography apparatus system to a steady state performed in the above step S4 will be described below with reference to the flowchart shown in FIG.

First, after the measurement condition setting in step S3 shown in FIG. 2 is completed, all the branch valves connected to the column are opened (step S11). That is, the branch valves of the valve 31 and the valve 32 shown in FIG. 1 are all opened.

Subsequently, the initially set carrier solution is sent out to all the columns A to F as the stationary phase (step S12). As a result, the carrier solution, which is the mobile phase, can all flow from the liquid sending section 1 through all the columns A to F of the separation section 3 to the detection section 4.

Next, the controller 5 receives the electric signal from the detector 4 (Step S13). The control unit 5 compares the fluctuation rates of the electric signals obtained by the detection unit 4 when the carrier solution as the mobile phase passes through the column.

Next, the controller 5 controls the received electric signal D
Then, it is determined whether or not the fluctuation rate of No. 1 has become equal to or less than a predetermined value (step S14). Here, if the fluctuation rate becomes equal to or less than the predetermined value, it is determined that the inside of the high performance liquid chromatography system is in a steady state, and the process proceeds to step S5 shown in FIG. 2 to start the screening process.

As described above, when the inside of the high performance liquid chromatography system is brought into a steady state, the steady state can be achieved in a short time by simultaneously flowing the carrier solution as the carrier solution through all the columns. it can.

Next, the flow of the screening process for column selection performed in step S5 shown in FIG. 2 will be described below with reference to the flowchart shown in FIG. Here, as described above, the screening process is performed on six columns.

First, only the branch valves of the valves 31 and 32 connected to the first column in the screening order of the column set in step S3 of the flowchart shown in FIG. 2 are opened (step S2).
1).

Subsequently, a sample liquid containing an analysis target is injected from the sample injection section 2 (step S22). As a result, in a state in which the sample solution is injected into the carrier solution sent from the liquid sending unit 1, the carrier solution flows into the column in which the branch valve of the separation unit 3 is open.

Next, the controller 5 receives the electric signal D1 from the detector 4 and stores it as data (step S2).
3). Here, the control unit 5 stores detection signals from the detectors A to C in the detection unit 4 as electric signals D1.

Subsequently, it is determined whether or not n = N (step S24). That is, since the number of columns is 6, it is determined whether or not N = 6.

In step S24, if n = N, the screening process is terminated, and the routine goes to step S6 in the flowchart shown in FIG.

On the other hand, if n ≠ N in step S24, the branch valve connected to the column currently performing the screening process is closed, and only the branch valve connected to the next column is opened. (Step S
25), the process proceeds to step S22 to inject the sample liquid,
Perform screening.

As described above, when the screening is completed for all of the six columns A to F set in the separation unit 3 and the screening of the carrier solution is also completed, all the data obtained by the detection unit 4 is deleted. Analyze the analysis target, what analysis conditions (measurement conditions)
Is optimal.

In the above high performance liquid chromatography apparatus, four types of carrier solutions (solutions A to D) were used as the mobile phase.
Liquid) was used, but the present invention is not limited to this. For example, various types of carrier solutions may be used as shown in FIG.

The mobile phase switching system shown in FIG. 5 comprises a mixer 51, a first degasser 52, a valve 53, and a second degasser 54.
The second degasser 54 is configured so that three types of carrier solutions, D-1 to D-6, are used as carrier solutions. Is configured to flow.

The mixer 51 is provided with four valves A to D. Thus, the carrier solution can be selectively caused to flow into the mixer 51 by controlling the opening and closing of the four valves.

The first degasser 52 is a member for degassing the carrier solution flowing into the mixer 51, and removes oxygen and other substances contained in the carrier solution. Thus, it is possible to prevent bubbles from being generated in the flow path of the high-performance liquid chromatography device.

The valve 53 is provided with open / close valves D-1 to D-6 corresponding to the six types of carrier solutions D-1 to D-6, and controls the open / close of the open / close valves. This allows the carrier solution to selectively flow into the mixer 51.

The second degasser 54 is connected to the first degasser 5
A member for degassing the carrier solution as in the case of 2.

According to such a mobile phase switching system, a plurality of types of carrier solutions can be selected, and a predetermined amount of each carrier solution is allowed to flow into the mixer 51 so that the carrier solution can be used in a mixed state. The number of combinations of the carrier solutions can be greatly increased.

Therefore, even when all the candidate columns have been screened and the next candidate column is set, the optimum carrier solution can be easily selected by combining the carrier solutions.

In the mobile phase switching system as described above, the open / close valves D-1 to D-6 of the valves A to C and the valve 53 provided in the mixer 51 are controlled based on the measurement conditions input to the control unit 5. Is controlled.

As described above, according to the high-performance liquid chromatography apparatus having the above configuration, when the column and the carrier solution are selected as the analysis conditions, the candidate column and the carrier solution can be automatically screened. It is possible to save the labor required for replacing the column and the carrier solution as in the related art.

Note that the configuration of the mobile phase switching system shown in FIG. 5 is merely an example of the present invention, and the specifications of the mixer and degasser may be appropriately selected and combined according to the type of mobile phase. .

Further, the high-performance liquid chromatography apparatus having the above-described configuration includes a plurality of types of columns and a plurality of types of carrier solutions, and these columns and the carrier solution can be appropriately selected and used. Thus, when analyzing multiple types of analytes, that is, when it is necessary to use multiple types of columns and multiple types of carrier solutions,
Since it is not necessary to exchange the column and the carrier solution for the apparatus, the time required for analyzing all the analytes can be greatly reduced.

[0115]

According to the first aspect of the present invention, there is provided a method for selecting analysis conditions.
As described above, in the analysis condition selection method of selecting an analysis condition suitable for an analyte to be analyzed by a high performance liquid chromatography apparatus, an analysis in which a sample solution containing the analyte is mixed with a carrier solution as a mobile phase is performed. The solution is sequentially supplied to a plurality of types of columns preset as a stationary phase,
This is a configuration in which analysis conditions suitable for the above-mentioned analyte are selected based on the result of analyzing the obtained separated solution.

Therefore, the analysis solution is sequentially supplied to a plurality of types of stationary phases set in advance, and the analysis conditions suitable for the analyte, that is, the column and the carrier solution are selected based on the obtained analysis results. So, as before,
There is no need to manually replace the column as the stationary phase or the carrier solution as the mobile phase, and the time required for selecting the column and the carrier solution can be greatly reduced.

According to the analysis condition selection method of the second aspect of the present invention, in addition to the configuration of the first aspect, after the supply of the analysis solution to all the columns is completed, the method is switched to another type of carrier solution. The analysis is performed again.

Therefore, in addition to the effect of the structure of claim 1, after the analysis solution is sent to all the columns, the carrier solution is switched and then sent out, so that the analysis target is analyzed using the same carrier solution. The product can be analyzed continuously by switching only the column.

Thus, when the analytes using different carrier solutions are screened in the same apparatus, the screening can be performed for each analyte measurable with the same carrier solution. This is effective in that the selection can be performed efficiently.

The method for selecting analysis conditions according to the third aspect of the present invention is, as described above, in addition to the configuration according to the first or second aspect, wherein the separated solution obtained in the column is analyzed by a plurality of types of detection methods. It is.

Therefore, in addition to the effects of the first and second aspects, by analyzing the separated solution by a plurality of types of detection methods, it is possible to determine whether or not the analysis conditions are suitable for the analyte. Since the determination can be made from the analysis result, there is an effect that the reliability of the correctness of the selection of the analysis conditions such as the column and the carrier solution can be improved.

As described above, the high performance liquid chromatography apparatus according to the fourth aspect of the present invention comprises a separation section comprising a plurality of types of columns as a stationary phase, a liquid sending section for sending a carrier solution as a mobile phase, and the liquid sending section. Analysis means for analyzing a separation solution obtained by supplying an analysis solution obtained by mixing a sample solution containing an analyte to a carrier solution sent from the section to each column of the separation section. Configuration.

Therefore, by preparing a column that forms the stationary phase and a carrier solution that forms the mobile phase in a type that can be set according to the analyte, it is possible to analyze a plurality of types of analytes. In addition, it is possible to save the trouble of replacing the column and the carrier solution, and as a result, it is possible to greatly reduce the total time required for the analysis.

In the high-performance liquid chromatography apparatus according to the fifth aspect of the present invention, as described above, in addition to the configuration of the fourth aspect, the liquid sending section is provided with a switching sending means for switching and sending a plurality of types of carrier solutions. The switching and sending means switches the carrier solution to be sent after the analysis solution is sent to all of the columns.

Therefore, in addition to the effect of the configuration of the fourth aspect, after the analysis solution is delivered to all the columns in the stationary phase by the switching delivery means, the carrier solution is switched and delivered, so that the same is achieved. An analyte to be analyzed using the carrier solution can be continuously analyzed by switching only the column.

Thus, when the analytes using different carrier solutions are analyzed by the same high-performance liquid chromatography apparatus, the analysis can be performed for each analyte measurable with the same carrier solution. There is an effect that the analysis of the object can be performed efficiently.

As described above, in the high performance liquid chromatography apparatus according to the sixth aspect of the present invention, in addition to the configuration of the fourth or fifth aspect, the analyzing means may further include an analyte contained in the separation solution obtained from the column. This is a configuration including a plurality of types of detectors for detection.

Therefore, in addition to the effect of the configuration of claim 4 or 5, it is possible to judge from the detection results of a plurality of detectors whether or not the analysis conditions are suitable for the analysis object. There is an effect that the analysis accuracy of the object can be improved.

As described above, the high performance liquid chromatography apparatus according to the seventh aspect of the present invention has a configuration in which the columns are connected in parallel in addition to the configuration of any of the fourth to sixth aspects.

Therefore, in addition to the effect of any one of claims 4 to 6, when the inside of the high performance liquid chromatography system is brought into a steady state by connecting the columns in parallel, the sending unit The delivered carrier solution can be simultaneously supplied to each column and can be simultaneously delivered to the analysis means. As a result, the time required for stabilization in the high-performance liquid chromatography system can be significantly reduced, and as a result, the total time required for detecting the analyte can be significantly reduced.

[Brief description of the drawings]

FIG. 1 is a schematic block diagram of a high-performance liquid chromatography apparatus used in the analysis condition selection method of the present invention.

FIG. 2 is a flowchart showing a flow of processing of an analysis condition selection method performed by the high performance liquid chromatography apparatus shown in FIG.

FIG. 3 is a flowchart showing a flow of an apparatus stabilization process in the analysis condition selection method shown in FIG. 2;

FIG. 4 is a flowchart showing a flow of a screening process in the analysis condition selection method shown in FIG. 2;

FIG. 5 is an explanatory diagram showing an example of a mobile phase switching system in a liquid sending unit provided in the high performance liquid chromatography device shown in FIG.

[Explanation of symbols]

 DESCRIPTION OF SYMBOLS 1 Liquid sending part 2 Sample injection part 3 Separation part 4 Detection part (analysis means) 5 Control part 11 Valve (switching transmission means) 31 valve 32 valve

 ──────────────────────────────────────────────────続 き Continuing from the front page (72) Inventor Tatsuo Harada 2-10-1 Tsukahara, Takatsuki City, Osaka Prefecture Inside Sumitomo Kagaku Kogyo Co., Ltd. (72) Inventor Shinji Morimoto 2-10-1 Tsukahara, Takatsuki City, Osaka Prefecture No. Sumitomo Chemical Co., Ltd. F-term (reference) 4D017 BA03 CB01 DA03 EA05 EB01

Claims (7)

[Claims] An analysis condition selection method for selecting an analysis condition suitable for an analyte to be analyzed by a high-performance liquid chromatography apparatus, wherein a sample solution containing the analyte is mixed with a carrier solution as a mobile phase. The analysis is characterized in that the solution is sequentially supplied to a plurality of types of columns preset as a stationary phase, and based on the result of analyzing the obtained separated solution, analysis conditions suitable for the analyte are selected. Condition selection method. 2. The method according to claim 1, wherein after the supply of the analysis solution to all of the columns is completed, the analysis is performed again by switching to another type of carrier solution. 3. The method according to claim 1, wherein the separation solution obtained in the column is analyzed by a plurality of types of detection methods. 4. A separation section comprising a plurality of types of columns as a stationary phase, a liquid sending section for sending a carrier solution as a mobile phase, and an analyte contained in the carrier solution sent from the liquid sending section. A high-performance liquid chromatography apparatus comprising: an analysis means for supplying an analysis solution obtained by mixing a sample solution to each column of the separation section and analyzing the separation solution obtained. 5. The liquid sending section is provided with switching sending means for switching and sending a plurality of types of carrier solutions, and the switching sending means sends after the analysis solution has been sent to all of the columns. The high-performance liquid chromatography apparatus according to claim 4, wherein the carrier solution is switched. 6. The method according to claim 4, wherein the analysis means includes a plurality of types of detectors for detecting an analyte contained in the separation solution obtained from the column. High performance liquid chromatography equipment. 7. The high performance liquid chromatography apparatus according to claim 4, wherein said columns are connected in parallel.