阅读说明：本技术 液相色谱仪以及溶出试验系统 (Liquid chromatograph and dissolution test system ) 是由 伴野太一 入来隆之 舍川知広 渡辺覚 于 2017-08-25 设计创作，主要内容包括：在线HPLC溶出试验系统包括溶出试验机以及液相色谱仪。所述液相色谱仪的自动取样器经由配管与所述溶出试验机连接,且具有：流动小瓶,将从所述溶出试验机供给的样品液收容在内部；取样针,用于从所述流动小瓶抽吸样品液并进行采集；以及注入端口,用于从所述取样针向所述分析流路注入样品液。所述液相色谱仪的控制部具有实时分析动作执行部,所述实时分析动作执行部构成为在从所述溶出试验机向所述流动小瓶供给样品液时,使所述自动取样器执行实时分析动作,即利用所述取样针抽吸所述流动小瓶内的样品液并直接注入所述注入端口。(The on-line HPLC dissolution test system comprises a dissolution tester and a liquid chromatograph. The automatic sampler of the liquid chromatograph is connected to the dissolution tester via a pipe, and includes: a flow vial for containing a sample liquid supplied from the dissolution testing machine; a sampling needle for aspirating and collecting sample fluid from the flow vial; and an injection port for injecting a sample liquid from the sampling needle into the analysis channel. The control unit of the liquid chromatograph includes a real-time analysis operation execution unit configured to cause the automatic sampler to execute a real-time analysis operation of sucking the sample liquid in the flow vial by the sampling needle and directly injecting the sample liquid into the injection port when the sample liquid is supplied from the dissolution test apparatus to the flow vial.)

1. A liquid chromatograph comprising:

an analysis flow path for the flow of the mobile phase;

an automatic sampler for injecting a sample liquid supplied from a dissolution tester into the analysis flow path;

an analysis column for separating components in the sample liquid injected into the analysis flow path by the autosampler;

a detector for detecting the sample components separated by the analytical column; and

a control unit for controlling at least the operation of the automatic sampler;

the automatic sampler has: a flow vial connected to the dissolution tester via a pipe and containing a sample liquid supplied from the dissolution tester inside; a sampling needle for aspirating and collecting sample fluid from the flow vial; and an injection port for injecting a sample liquid from the sampling needle into the analysis channel;

the control unit includes a real-time analysis operation execution unit configured to cause the auto-sampler to execute a real-time analysis operation of sucking the sample liquid in the flow vial by the sampling needle and directly injecting the sample liquid into the injection port, when the sample liquid is supplied from the dissolution testing machine to the flow vial.

2. The liquid chromatograph of claim 1, wherein

The autosampler further having a collection container for fractionating and collecting sample liquid collected from the flow vial using the sampling needle,

the control unit further includes: a collection operation execution unit configured to cause the automatic sampler to execute a collection operation of sucking the sample liquid in the flow vial by the sampling needle and discharging the sample liquid from the sampling needle to the collection container, when the sample liquid is supplied from the dissolution testing machine to the flow vial; and a collected sample analyzing operation executing unit configured to cause the automatic sampler to execute a collected sample analyzing operation of sucking the sample liquid collected in the collection container by the sampling needle and injecting the sample liquid into the injection port.

3. The liquid chromatograph of claim 2, further comprising:

a mode selection unit configured to select either a real-time analysis mode or a collection analysis mode based on an input instruction from an operator,

the real-time analysis operation execution unit is configured to cause the auto-sampler to execute the real-time analysis operation when the real-time analysis mode is selected by the mode selection unit,

the collection operation execution unit and the collected sample analysis operation execution unit are configured to cause the auto-sampler to execute the collection operation and the collected sample analysis operation, respectively, when the collection analysis mode is selected by the mode selection unit.

4. A dissolution test system comprising:

a dissolution testing machine; and

the liquid chromatograph according to any one of claims 1 to 3, connected to the dissolution tester via a pipe.

5. The dissolution test system of claim 4, wherein

The liquid chromatograph further includes an analysis state communication unit configured to determine whether or not the liquid chromatograph is in an analysis operation, and transmit an analysis state signal related to whether or not the liquid chromatograph is in the analysis operation to the dissolution tester, and the analysis state communication unit is configured to determine whether or not the liquid chromatograph is in the analysis operation

The dissolution testing machine includes a communication unit that receives the analysis state signal transmitted by the analysis state communication unit, and is configured to start the dissolution test on a new sample when the liquid chromatograph is in an analysis operation and start the dissolution test on the new sample when the analysis operation of the liquid chromatograph is finished, based on the analysis state signal received by the communication unit, when it is set to continuously perform the dissolution test on a plurality of samples.

6. A dissolution test system comprising:

a dissolution testing machine for performing dissolution testing of a sample; and

a liquid chromatograph includes: an analysis flow path for the flow of the mobile phase; an automatic sampler for injecting the sample liquid supplied from the dissolution tester into the analysis channel; an analysis column for separating components in the sample liquid injected into the analysis flow path by the autosampler; a detector for detecting the sample components separated by the analytical column; a control unit for controlling at least the operation of the automatic sampler; and an analysis state communication unit configured to determine whether or not the liquid chromatograph is in an analysis operation, and to transmit an analysis state signal relating to whether or not the liquid chromatograph is in the analysis operation to the dissolution tester; and is

The dissolution testing machine includes a communication unit that receives the analysis state signal transmitted by the analysis state communication unit, and is configured to start the dissolution test on a new sample when the liquid chromatograph is in an analysis operation and start the dissolution test on the new sample when the analysis operation of the liquid chromatograph is finished, based on the analysis state signal received by the communication unit, when it is set to continuously perform the dissolution test on a plurality of samples.

7. A liquid chromatograph used in the dissolution test system according to claim 6, and comprising:

an analysis flow path for the flow of the mobile phase; an automatic sampler for injecting the sample liquid supplied from the dissolution tester into the analysis channel; an analysis column for separating components in the sample liquid injected into the analysis flow path by the autosampler; a detector for detecting the sample components separated by the analytical column; a control unit for controlling at least the operation of the automatic sampler; and an analysis state communication unit configured to determine whether or not the liquid chromatograph is in an analysis operation, and to transmit an analysis state signal relating to whether or not the liquid chromatograph is in the analysis operation to the dissolution tester; and performing an analysis operation on the new sample when the dissolution tester starts the dissolution test on the new sample.

8. A dissolution testing machine used in the dissolution testing system according to claim 6, and

the analyzing apparatus includes a communication unit that receives the analysis state signal transmitted by the analysis state communication unit, and is configured to start the elution test for a new sample when the liquid chromatograph is in the analyzing operation and to start the elution test for the new sample when the analyzing operation of the liquid chromatograph is completed, based on the analysis state signal received by the communication unit, when it is set to continuously perform the elution test for a plurality of samples.

Technical Field

The present invention relates to a liquid chromatograph for online analysis of a test solution of a dissolution tester and a dissolution test system including the liquid chromatograph (hereinafter referred to as an online High Performance Liquid Chromatograph (HPLC) dissolution test system).

Background

An automatic dissolution testing machine having a fraction function and an on-line measurement function using an Ultraviolet (UV) spectrometer is expected to grow in a high market scale in the future. The dissolution tester is usually connected to a UV spectrometer, and the concentration of a specific component in a sample liquid from the dissolution tester is measured by the UV spectrometer at every predetermined timing, thereby measuring the dissolution rate of a sample such as an internal solid preparation into a liquid.

On the other hand, in an elution test of an oral solid preparation, a liquid chromatograph is sometimes used when it is difficult to perform a correct elution test using a UV spectrometer due to the influence of a plurality of components and excipients (see patent document 1). In this case, a flow vial may be provided in an automatic sampler of the liquid chromatograph so that the sample liquid of the dissolution tester can be introduced into the liquid chromatograph on-line. Such a dissolution test system is called an on-line hplc dissolution test system.

Disclosure of Invention

Problems to be solved by the invention

Since a conventional liquid chromatograph requires a long time for one analysis, the analysis rate of the liquid chromatograph may not keep up with the sampling rate of the sample liquid from the dissolution tester. Therefore, in a conventional online HPLC elution test system, a sample liquid supplied from an elution tester is temporarily collected in an empty collection container, and the sample liquid is collected from the collection container and injected into an analysis channel to start analysis at a timing at which a liquid chromatograph is in an analyzable state. Therefore, there is a problem that the efficiency of the dissolution test is poor.

In recent years, the speed of analysis by liquid chromatographs has been increasing, and the time required for one analysis has been rapidly shortened compared with the conventional one. Further, a fully automatic dissolution test machine capable of performing a continuous dissolution test of a plurality of types of oral solid preparations is being developed. From such a background, it is considered that an elution test can be performed more efficiently by combining a fully automatic elution tester with a liquid chromatograph whose analysis speed is increased.

Therefore, an object of the present invention is to enable an elution test to be performed more efficiently than in the past by using a liquid chromatograph.

Means for solving the problems

The liquid chromatograph of the present invention comprises: an analysis flow path for the flow of the mobile phase; an automatic sampler for injecting a sample liquid supplied from a dissolution tester into the analysis flow path; an analysis column for separating components in the sample liquid injected into the analysis flow path by the autosampler; a detector for detecting the sample components separated by the analytical column; and a control unit for controlling at least the operation of the auto-sampler.

Further, the autosampler has: a flow vial connected to the dissolution tester via a pipe and containing a sample liquid supplied from the dissolution tester inside; a sampling needle for aspirating and collecting sample fluid from the flow vial; and an injection port for injecting a sample liquid from the sampling needle into the analysis channel. Further, the control unit includes a real-time analysis operation execution unit configured to cause the auto-sampler to execute a real-time analysis operation of sucking the sample liquid in the flow vial by the sampling needle and directly injecting the sample liquid into the injection port, when the sample liquid is supplied from the dissolution test apparatus to the flow vial.

That is, the liquid chromatograph according to the present invention employs a real-time analysis method in addition to or instead of the conventional analysis method, which is the following analysis method: the method for analyzing a sample solution in real time includes the steps of temporarily collecting a sample solution supplied from a dissolution testing machine in a collection vessel, and sucking a sample from the collection vessel and injecting the sample into an analysis channel at a timing at which analysis can be performed by a liquid chromatograph, wherein the real-time analysis method is an analysis method including: the sample liquid supplied from the dissolution testing machine was sucked by a sampling needle and directly injected into the injection port without passing through the collection container. This is achieved by increasing the analysis rate of the liquid chromatograph, and it is a precondition that the analysis of the liquid chromatograph is performed at a rate higher than the sampling rate of the dissolution tester. Since the sample liquid supplied from the dissolution test apparatus is directly injected into the injection port without passing through the collection vessel, the operation of discharging the sample liquid into the collection vessel by the sampling needle and the operation of sucking the sample liquid from the collection vessel again and injecting the sucked sample liquid into the injection port are omitted, and the dissolution test can be efficiently performed. Further, since the sample solution sampled from the dissolution tester can be immediately analyzed by the liquid chromatograph, the results of the dissolution test can be quickly obtained.

In the liquid chromatograph of the present invention, it is preferable that the elution test of the conventional embodiment is also performed, that is, the sample liquid supplied from the elution tester is temporarily collected in a collection container, and the sample is sucked from the collection container and injected into the analysis channel at a timing at which the analysis can be performed by the liquid chromatograph. In the conventional dissolution test in which a sample liquid is temporarily collected in a collection vessel, there is an advantage that the sample liquid can be stored in the collection vessel. This approach is an effective approach in the following cases: it is desired to carefully observe the change with time of the dissolution rate of the sample (in a cycle shorter than the analysis time of the liquid chromatograph), or to observe the sample as a compound having a long analysis time or a compound requiring dilution. Therefore, if the dissolution test of the conventional method can be performed, the dissolution test can be performed under appropriate conditions according to the sample.

In a specific configuration of the above aspect, the auto-sampler includes a collection container for fractionating and collecting a sample liquid collected from the flow vial by the sampling needle, and the control unit further includes: a collection operation execution unit configured to cause the automatic sampler to execute a collection operation of sucking the sample liquid in the flow vial by the sampling needle and discharging the sample liquid from the sampling needle to the collection container, when the sample liquid is supplied from the dissolution testing machine to the flow vial; and a collected sample analysis operation execution unit configured to cause the automatic sampler to execute a collected sample analysis operation of sucking the sample liquid collected in the collection container by the sampling needle and injecting the sample liquid into the injection port.

Further, the liquid chromatograph of the present invention preferably further includes a mode selection unit configured to select either one of a real-time analysis mode and a collection analysis mode based on an input instruction from an operator. In this case, the real-time analysis operation execution unit is configured to cause the auto-sampler to execute the real-time analysis operation when the real-time analysis mode is selected by the mode selection unit, and the collection operation execution unit and the collected sample analysis operation execution unit are configured to cause the auto-sampler to execute the collection operation and the collected sample analysis operation, respectively, when the collection analysis mode is selected by the mode selection unit. Thus, the operator can freely select the real-time analysis mode and the collection analysis mode, and the degree of freedom of setting the conditions of the dissolution test is increased.

The dissolution test system of the present invention includes a dissolution tester and the liquid chromatograph connected to the dissolution tester via a pipe.

As described above, a fully automatic dissolution test machine capable of automatically and continuously performing dissolution tests of a plurality of types of internal solid pharmaceutical preparations has been developed, but such a fully automatic dissolution test machine is generally combined with a UV spectrometer, and cannot be combined with a liquid chromatograph to perform a fully automatic continuous dissolution test. Therefore, in the case where there are a plurality of solid preparations having a solid preparation of a plurality of components, the actor must monitor the analysis state of the liquid chromatograph, and when the liquid chromatograph becomes an analyzable state, start the dissolution test of a new sample.

Therefore, in the dissolution test system of the present invention, it is preferable that the fully automatic dissolution test machine and the liquid chromatograph are linked, and even when there are a plurality of solid preparations having solid preparations of a plurality of components, the dissolution test of the solid preparations can be performed fully automatically and continuously.

That is, in the dissolution test system according to the present invention, it is preferable that the liquid chromatograph includes an analysis state communication unit configured to determine whether or not the liquid chromatograph is in an analysis operation, and transmit an analysis state signal related to whether or not the liquid chromatograph is in the analysis operation to the dissolution tester, and the dissolution tester includes a communication unit configured to receive the analysis state signal transmitted by the analysis state communication unit, and is configured to start the dissolution test for a new sample when the liquid chromatograph is in the analysis operation, and start the dissolution test for the new sample when the analysis operation of the liquid chromatograph is finished, based on the analysis state signal received by the communication unit, in a case where it is set that the dissolution tests for a plurality of samples are continuously executed. In this case, since the dissolution test machine automatically starts the dissolution test for the next sample when the liquid chromatograph is in an analyzable state, the operator can automatically and continuously perform the dissolution test for a plurality of samples without monitoring the analytical state of the liquid chromatograph.

In addition, the liquid chromatograph used in the dissolution test system preferably includes: an analysis flow path for the flow of the mobile phase; an automatic sampler for injecting the sample liquid supplied from the dissolution tester into the analysis channel; an analysis column for separating components in the sample liquid injected into the analysis flow path by the autosampler; a detector for detecting the sample components separated by the analytical column; a control unit for controlling at least the operation of the automatic sampler; and an analysis state communication unit configured to determine whether or not the liquid chromatograph is in an analysis operation, transmit an analysis state signal related to whether or not the liquid chromatograph is in the analysis operation to the dissolution tester, and perform the analysis operation on the new sample when the dissolution tester starts the dissolution test on the new sample.

In the dissolution test apparatus used in the dissolution test system, it is preferable that the dissolution test apparatus includes a communication unit that receives the analysis state signal transmitted by the analysis state communication unit, and when it is set to continuously perform dissolution tests on a plurality of samples, the dissolution test apparatus is configured not to start the dissolution test on a new sample when the liquid chromatograph is in the analysis operation, and to start the dissolution test on the new sample when the analysis operation of the liquid chromatograph is finished, based on the analysis state signal received by the communication unit.

ADVANTAGEOUS EFFECTS OF INVENTION

In the liquid chromatograph and the dissolution test system of the present invention, since the sample liquid supplied from the dissolution tester is directly injected into the injection port, the dissolution test can be performed efficiently. Further, since the sample solution sampled from the dissolution tester can be immediately analyzed by the liquid chromatograph, the results of the dissolution test can be quickly obtained.

Drawings

FIG. 1 is a schematic configuration diagram showing an example of an on-line HPLC dissolution test system.

Fig. 2 is a schematic partial sectional configuration diagram showing an example of the configuration in the auto-sampler of the embodiment.

Fig. 3 is a flowchart for explaining an example of the real-time analysis operation according to the embodiment.

Fig. 4 is a flowchart for explaining an example of the collecting operation according to the embodiment.

FIG. 5 is a flowchart for explaining an example of the collected sample analyzing operation according to the embodiment.

FIG. 6 is a flowchart for explaining an example of the operation of the full-automatic continuous dissolution test according to the above embodiment.

Detailed Description

Hereinafter, an embodiment of a liquid chromatograph, an elution tester, and an elution test system according to the present invention will be described with reference to the drawings.

The on-line HPLC dissolution test system of the example comprises: an elution tester 2, a liquid chromatograph 4, and an arithmetic processing device 6. Although not shown, the dissolution testing machine 2 has at least one test container for storing a sample such as a drug together with a liquid, and is configured to supply the liquid in the test container as a sample liquid to the automatic sampler 10 of the liquid chromatograph 4 via the inlet pipe 16 at predetermined intervals. The arithmetic processing unit 6 is electrically connected to the control unit 20 of the dissolution tester 2 via a communication interface 24 (communication unit), and is electrically connected to the control unit 22 of the liquid chromatograph 4 via a communication interface 26.

The arithmetic processing unit 6 is realized by, for example, a dedicated computer or a general-purpose personal computer. The operator can collectively manage the entire on-line HPLC elution test system by using the arithmetic processing unit 6. The control unit 20 of the dissolution test apparatus 2 is realized by a microcomputer provided for controlling the operation of each member provided in the dissolution test apparatus. The control unit 22 of the liquid chromatograph 4 is realized by, for example, a system controller that manages the operations of the respective modules 8, 10, 12, and 14 of the liquid chromatograph 4.

The liquid chromatograph 4 includes: a liquid feeding device 8, an autosampler 10, a column oven 12, a detector 14, and a controller 22.

The liquid feeding device 8 is a device for feeding a mobile phase by using a liquid feeding pump. The outlet of the liquid feeding device 8 is connected to an auto-sampler 10 via a pipe.

The autosampler 10 is configured to inject a sample liquid supplied from the dissolution tester 2 into an analysis flow path through which a mobile phase flows from the liquid feeder 8. The configuration of the auto-sampler 10 will be described later.

An analytical column (not shown) for separating a sample for each component is housed in the column oven 12. The analytical column in the column oven 12 is connected to the outlet of the auto-sampler 10 via a pipe, and the sample injected by the auto-sampler 10 is introduced into the analytical column together with the mobile phase from the liquid feeding device 8. The downstream end of the analytical column in the column oven 12 is connected to the detector 14 via a pipe.

The detector 14 is for detecting the sample components separated by the analytical column and is, for example, an ultraviolet absorbance detector. The detector signal obtained by the detector 14 is taken into the arithmetic processing unit 6 and used for quantifying the concentration of the sample component and the like.

Here, a schematic configuration of the auto-sampler 10 will be described with reference to fig. 2.

Disposed within the auto-sampler 10 are a sampling needle 38, an injection port 40, a collection container 42, and a flow vial 44. In the figure, only one collection container 42 and flow vial 44 are shown for convenience, but a plurality of collection containers 42 and flow vials 44 are actually provided. The number of collection containers 42 and flow vials 44 is not limited. The flow vials 44 are held by a flow vial rack 46.

Injection port 40 is used for sampling needle 38 to inject sample fluid into the analytical flow path of the mobile phase flow. The injection port 40 is configured to insert the tip end of the sampling needle 38 and connect the sampling needle 38 liquid-tightly.

The collection container 42 is a container for fractionating and collecting the sample liquid collected by the sampling needle 38 from the flow vial 44.

The flow vial 44 includes a flow vial body 48 and a cap 50 mounted to an upper portion of the flow vial body 48. The flow vial body 48 is provided with a space 48a for storing a sample liquid, an inlet 54 as a flow path communicating with the bottom of the space 48a, and an outlet 56 as a flow path communicating with the upper part of the space 48 a. The inlet pipe 16 is connected to the inlet 54, and the outlet pipe 18 is connected to the outlet 56. The upper opening of the flow vial body 48, the opening of which is sealed by a septum 52 comprising an elastic material, and a cap 50 is mounted on the upper portion of the flow vial body 48 to press the septum 52. An opening to the partition 52 is provided in the upper surface of the cap 50. The opening of the partition plate 52 is used to guide the sampling needle 38, which is lowered from above, to the space 48a inside the flow vial body 48. The sampling needle 38, which descends through the opening of the cap 50, penetrates the partition plate 52 and enters the front end into the space 48a in the flow vial body 48 to aspirate the sample liquid.

Sampling needle 38 is disposed above injection port 40, collection container 42, and flow vial shelf 46. The sampling needle 38 is moved in the horizontal plane direction and the vertical direction with its tip end being directed vertically downward by a movement mechanism not shown.

The operation mode of the liquid chromatograph 4 includes two modes, a real-time analysis mode and a collection analysis mode. The real-time analysis action is performed in a real-time analysis mode, in which the sampling needle 38 of the auto-sampler 10 draws a sample from the flow vial 44 and injects it directly into the injection port 40. On the other hand, in the collection and analysis mode, a collection action in which the sampling needle 38 sucks the sample liquid from the flow vial 44 and collects the sample liquid to the collection container 42, and a collection and sample analysis action in which the sampling needle 38 sucks the sample liquid from the collection container 42 and injects it into the injection port 40 are performed.

Thereafter, the sample liquid injected through the injection port 40 is introduced into the detector 14 through the analytical column in the column oven 12 by the mobile phase from the liquid feeding device 8. Further, although not shown in fig. 2, in the automatic sampler 10, a standard sample container that contains a standard sample for quantifying the concentration of a specific component in sample water is provided, and the sampling needle 38 may aspirate the standard sample from the standard sample container and inject it into the injection port 40.

Referring back to FIG. 1, an embodiment of the on-line HPLC dissolution test system will be described. The control unit 22 of the liquid chromatograph 4 includes: a mode selection unit 28, a real-time analysis operation execution unit 30, a collection operation execution unit 32, a collected sample analysis operation execution unit 34, and an analysis state communication unit 36. The respective units 28, 30, 32, 34, and 36 are functions obtained by executing a predetermined program by an arithmetic element such as a microcomputer provided in the control unit 22.

The mode selection unit 28 is configured to select either one of the real-time analysis mode and the collection analysis mode as the operation mode of the liquid chromatograph 4 based on an input command from an operator. That is, the operator can designate either the real-time analysis mode or the collection analysis mode as the operation mode of the liquid chromatograph 4 for the dissolution test of a certain sample.

As described above, the real-time analysis mode is a mode as follows: when the sample liquid is supplied from the dissolution testing machine 2 to the flow vial 44 of the auto-sampler 10, the auto-sampler is caused to perform a real-time analysis operation in which the sample liquid is sucked by the sampling needle 38 and directly injected into the injection port 40. That is, the real-time analysis mode is a mode as follows: when the sample liquid is supplied from the dissolution tester 2 to the flow vial 44 of the autosampler 10, the analysis is started in real time by the liquid chromatograph. On the other hand, the collection analysis mode is a mode as follows: when a sample liquid is supplied from the dissolution testing machine 2 to the flow vial 44 of the auto-sampler 10, the auto-sampler is caused to perform a collection operation of sucking the sample liquid by the sampling needle 38 and collecting the sample liquid in an empty collection container 42, and a collected sample analysis operation of collecting the sample liquid from the collection container 42 by the sampling needle 38 at a predetermined timing and injecting the collected sample liquid into the injection port 40.

The operation mode of the liquid chromatograph 4 can be set for each sample. That is, when there are a plurality of samples to be subjected to the elution test, the operation mode of the liquid chromatograph 4 for the elution test of each sample can be set.

The real-time analysis operation execution unit 30 is configured to cause the auto-sampler 10 to execute the measurement analysis operation when the real-time analysis mode is selected by the mode selection unit 28.

The collection operation execution unit 32 and the collected sample analysis operation execution unit 34 are configured to cause the auto-sampler 10 to execute the collection operation and the collected sample analysis operation, respectively, when the collection analysis mode is selected by the mode selection unit 28.

The analysis state communication unit 36 is configured to determine whether or not the liquid chromatograph 4 is under analysis, and to transmit an analysis state signal related to the determination result to the dissolution tester 2 directly or indirectly via the arithmetic processing device 6. Whether or not the liquid chromatograph 4 is under analysis can be determined by whether or not a preset analysis time has elapsed, whether or not a last peak of the chromatograph obtained from the detection signal of the detector 14 has occurred, or the like.

Next, a real-time analysis operation of the liquid chromatograph 4 in the real-time analysis mode will be described with reference to flowcharts of fig. 1, 2, and 3.

First, before starting the dissolution test of the sample, a standard sample in which the concentration of a specific component is known is analyzed, and the measurement data thereof is recorded (step S1). After the analysis of the standard sample is finished, the dissolution test of the sample of the dissolution tester 2 is started. The sample liquid is supplied from the dissolution testing machine 2 to the flow vial 44 of the autosampler 10 at predetermined timings (for example, at regular intervals) (step S2). When the sample liquid is supplied to the flow vial 44, a signal indicating that the sample liquid is supplied is transmitted from the control unit 20 of the dissolution tester 2 to the control unit 22 of the liquid chromatograph 4.

When the sample liquid is supplied from the dissolution testing machine 2 to the flow vial 44, the real-time analysis operation execution unit 30 causes the auto-sampler 10 to execute the following operations: the sample liquid of the flow vial 44 is aspirated by the sampling needle 38 and injected directly into the injection port 40 (steps S3 and S4). The sample injected into the injection port 40 is introduced into the analysis flow path through which the mobile phase flows from the liquid feeding device 8, and is analyzed by the liquid chromatograph (step S5). The above operations of step S1 to step S5 are repeatedly executed the number of times set in advance by the operator (step S6).

Next, the collecting operation of the liquid chromatograph 4 in the collection analysis mode will be described with reference to flowcharts of fig. 1, 2, and 4.

The dissolution test of the sample of the dissolution tester 2 was started. The sample liquid is supplied from the dissolution testing machine 2 to the flow vial 44 of the autosampler 10 at a predetermined timing (step S11).

When the sample liquid is supplied from the dissolution testing machine 2 to the flow vial 44, the collection operation executing unit 32 causes the auto-sampler 10 to execute the following operations: the sample liquid in the vial 44 is sucked by the sampling needle 38, and discharged to and collected in the empty collection container 42 (steps S12 and S13). The above operations of step S11 to step S13 are repeatedly executed the number of times set in advance by the operator (step S14).

Next, a collected sample analysis operation of the liquid chromatograph 4 in the collection analysis mode will be described with reference to flowcharts of fig. 1, 2, and 5.

The collected sample analyzing operation may be performed at any timing after the unanalyzed sample liquid is collected in at least one of the collection containers. The operator can arbitrarily set the timing of the event collection sample analysis operation.

As in the real-time analysis mode, a standard sample having a known concentration of a specific component is analyzed before the start of the dissolution test of the sample, and the measurement data thereof is recorded (step S21). Thereafter, when the unanalyzed sample liquid is collected in the collection container 42 (step S22), the collected sample analysis operation execution unit 34 determines whether the liquid chromatograph 4 is in an analyzable state, that is, whether the liquid chromatograph 4 is analyzing (step S23). When the liquid chromatograph 4 is in an analyzable state, the collected sample analysis operation execution unit 34 causes the auto-sampler 10 to execute the following operations: the sample liquid is sucked from the collection container 42 by the sampling needle 38 and injected into the injection port 40 (steps S24 and S25). The sample injected into the injection port 40 is introduced into the analysis flow path through which the mobile phase flows from the liquid feeding device 8, and is analyzed by the liquid chromatograph (step S26). The above operations of step S22 to step S26 are repeated for the number of collection containers in which the unanalyzed sample liquid is collected.

In the online HPLC elution test system of the above embodiment, the elution test machine 2 and the liquid chromatograph 4 are configured to communicate with each other and to be interlocked with each other, thereby enabling a fully automatic continuous elution test for a plurality of samples. As a precondition for this, the dissolution tester 2 may be provided with a plurality of samples. The dissolution tester 2 is configured to, when a plurality of types of samples are set, sequentially introduce each sample into a test vessel and automatically perform a dissolution test on the sample.

An example of the operation of the fully automatic continuous dissolution test will be described with reference to the flowcharts of fig. 1 and 6.

First, the operator prepares for a full-automatic continuous dissolution test (step S31). The preparation refers to setting of samples in the dissolution tester 2, setting of conditions for dissolution test of each sample, and the like. After the preparation is completed, when the operator inputs an instruction to start the dissolution test via the arithmetic processing unit 6, the control unit 20 of the dissolution tester 2 determines whether or not the liquid chromatograph 4 is in an analyzable state based on the analysis state signal transmitted from the analysis state communication unit 36 of the liquid chromatograph 4 (step S32), and starts the dissolution test of the sample when the liquid chromatograph 4 is in an analyzable state (step S33).

After the start of the dissolution test, the sample liquid is supplied from the dissolution tester 2 to the autosampler 10 of the liquid chromatograph 4 at a timing set by the operator, and the autosampler 10 samples the sample liquid (step S34). The analysis operation by the liquid chromatograph 4 is as described in fig. 3 to 5. When the number of sampling times of the sample liquid reaches the preset number, the dissolution tester 2 ends the dissolution test (step S35), and the test vessel is cleaned (step S36). Since the liquid chromatograph 4 transmits the analysis state signal to the dissolution tester, when the analysis is completed, the analysis state signal whose content is not under analysis but a state in which the next sample can be analyzed is transmitted to the dissolution tester.

When there is a sample to be subjected to the dissolution test next (step S37), it is checked whether or not the liquid chromatograph 4 is in an analyzable state based on the analysis state signal transmitted from the analysis state communication unit 36 of the liquid chromatograph 4 (step S32), and when the liquid chromatograph 4 is in a state in which a new sample can be analyzed, the new sample is introduced into the test vessel and the dissolution test is started (step S33). The liquid chromatograph 4 performs the analysis action on the next new sample in the same manner as described. When a plurality of samples are set in the dissolution testing machine 2 in this manner, the operations of step S32 to step S36 are automatically executed until the dissolution tests of all the samples are completed.

Description of the symbols

2: sample processing device

4: liquid chromatograph

6: arithmetic processing device

8: liquid feeding device

10: automatic sampler

12: column oven

14: detector

16: inlet pipe

18: outlet piping

20. 22: control unit

24. 26: interface for communication

28: mode selection unit

30: real-time analysis action execution unit

32: collecting action executing part

34: collected sample analysis operation execution unit

36: analysis state communication unit

38: sampling needle

40: injection port

42: collecting container

44: flow vial

46: shelf for mobile vials

48: flow vial body

50: cap cap

52: partition board

54: inlet section

56: and an outlet part.