JP2000019154A - Preparative liquid chromatograph mass spectrometer - Google Patents

Abstract

PROBLEM TO BE SOLVED: To preparatively isolate even a trace quantity of a sample without wasting the sample by recovering sample components while changing a collecting container provided in an opposed position to a spray part, every sample component. SOLUTION: A sample component separated in a column 1 flows through a passage and reaches a spray part 7a of an interface part 7, and the sample component is sprayed while being ionized by voltage applying mechanism of the spray part 7a. A part of the sprayed sample component passes through a sampling hole 8 and is detected by a detector 9 of a mass spectrometry part 6. The remaining greater part of the sample component is recovered into a collecting container 5 positioned on a turntable 11 opposedly to the spray part 7a. Upon detecting a specific component, the detector 9 sends a signal to a control part 10, and the turntable 11 is rotated receiving a signal from the control part 10. The collecting container 5 is changed every specific component to recover the sample component. The sample components can thus be recovered until there is no eluted component from the column 1.

Description

DETAILED DESCRIPTION OF THE INVENTION

[0001]

BACKGROUND OF THE INVENTION 1. Field of the Invention The present invention relates to a separation method in which a sample component is separated using a separation column of a liquid chromatograph, the separated component is detected by a mass spectrometer, and the specified component is separated and collected. The present invention relates to a liquid chromatograph mass spectrometer (preparative LCMS), and more particularly to a preparative LCMS suitable for fractionation of a small amount of a sample.

[0002]

2. Description of the Related Art A preparative liquid chromatograph is provided at the latter stage of a column in which a sample to be collected is separated for each component by a difference in elution time from a column in a liquid chromatograph section (LC section). By detecting the components of the sample separated by the detector, the sample can be separated for each component. Preparative LCMS using a mass spectrometer as a detector is excellent in that high-sensitivity separation of each component is possible.

FIG. 1 shows a conventional example of such a preparative LCMS. In the figure, 1 is a column of a liquid chromatograph unit,
2 is a splitter for branching a flow path, 3 is a switching valve, 4 is a sample outlet, 5 is a collection vessel, 6 is a mass spectrometer (MS section),
Reference numeral 7 denotes an interface unit for performing ionization under atmospheric pressure, 7a denotes a spray unit for performing ionization of a sample, 8
Is a sampling hole of the mass spectrometer, 9 is a detector of the mass spectrometer, and 10 is a control unit. In LCMS using a mass spectrometer as a detector, it is necessary to take out a part of the sample, ionize it, and perform mass spectrometry. Therefore, a detector (for example, a UV detector) cannot be provided in the middle of the flow path. Such a branch channel method is employed. This device operates as follows. That is, the sample separated for each component in the column 1 of the liquid chromatograph unit (LC unit) is branched by the splitter 2, a part of the sample is sent to the spray unit 7a of the interface unit 7 of the LCMS, and the other samples are It is sent to the switching valve 3. The sample that has reached the spray section 7a is ionized here, passes through the sampling hole 8, and is detected by the detection section 9. The signal from the detector 9 is sent to the control unit 10.

The time required for the components sent from the splitter 2 to the spray unit 7a to be ionized and detected is the same as the time required for the components sent from the splitter 2 to the switching valve 3 to reach the switching valve 3. The controller 10 sends a switching signal to the switching valve 3 when a specific component is detected by the detector 9 because the adjustment is made according to the length of the pipe and the like. As a result, the desired specific components are collected in the specific collection container 5, and collection is performed for each component in this manner.

[0005]

The preparative LC as described above
In MS, since the flow path after the splitter is composed of two flow paths, a certain amount of sample required to fill both flow paths is required. However, when there is only a small amount of a sample for preparative separation, preparative LCMS cannot be used due to a shortage of a sample amount even though highly sensitive preparative separation can be performed by preparative LCMS. Further, in the preparative LCMS, since the sample sent to the interface unit 7 and sprayed is completely consumed in the spray unit 7a, there is a problem that the trace sample is further reduced. Thus, the present invention is characterized by providing a preparative LCMS that can perform fractionation by a LCMS even with a small amount of a sample and can reduce the consumption of the sample.

[0006]

According to the preparative LCMS of the present invention which has been made to solve the above problems, a sample is separated into components by a separation column in a liquid chromatograph unit, and the separated components are detected by a mass spectrometric unit. A preparative LCMS that separates each component by spraying a sample component eluted from a separation column at atmospheric pressure and sends a part of the sample component to a mass spectrometry unit via a sampling hole; A mass spectrometer that performs mass spectrometry of the sample that has passed through the sampling hole, a plurality of exchange units that are exchangeably provided at positions facing the spray direction in order to collect the sample components sprayed in the interface unit, A control unit for exchanging the collection means in accordance with a signal from the analysis unit.

[0007]

DESCRIPTION OF THE PREFERRED EMBODIMENTS The present invention will be described below with reference to embodiments. FIG. 2 is a block diagram of a preparative LCMS showing one embodiment of the present invention. In the figure, 1 is a liquid chromatograph unit (L
Column C). The overall configuration of the liquid chromatograph unit other than the columns such as the liquid sending pump and the column oven is not shown. The outlet side of the column 1 is connected to the spray section 7a of the interface section 7 in a flow path. A spray unit such as an electrospray or an atmospheric pressure ionization spray that can be ionized under atmospheric pressure is used for the spray unit 7a.

[0008] The collection container 5 is installed at a position facing the spray unit 7a at a distance of about 5 cm. A plurality of the collection containers 5 are placed on the turntable 11,
The rotation of the turntable 11 causes one of them to stop at the position facing the spray portion 7a. In the space between the spray unit 7a and the collection container 5, there is a sampling hole 8 of a mass spectrometer 6 having a built-in quadrupole mass spectrometer in the lateral direction. Is to enter. That is, since the mass spectrometry unit 6 is maintained in a vacuum state by the turbo molecular pump (TMP), the ionized sample is sucked into the sampling hole 8 together with the air in the interface unit. The mass spectrometer 6 has a detector 9 for detecting ions, and a detection signal is sent to the controller 10. When a signal is sent from the control unit 10 to the drive motor of the turntable 11, the collection container 5 is replaced.

Next, the operation of the preparative LCMS will be described. The sample component separated in the column 1 flows through the flow path and reaches the spray section 7a of the interface section 7. The sample components are sprayed while being ionized by a voltage applying mechanism (not shown) of the spray unit 7a. A part of the sprayed sample component passes through the sampling hole 8 and is detected by the detector 9 of the mass spectrometer 6. Further, most of the remaining sprayed sample components are collected in the collection container 5 located at a position facing the spray section 7a. When the detector 9 detects the characteristic component, a signal from the detector 9 is sent to the control unit 10, and the turntable rotates in response to the signal from the control unit. Thereby, the collection container 5 is exchanged and collected for each specific component. In this manner, a sample is collected for each component until no components elute from the column.

In the present embodiment, a turntable is used for exchanging containers. However, the present invention is not limited to this, and a container exchanging mechanism using a robot hand may be used. Alternatively, as shown in FIG. 3, a microplate provided with a concave portion for collection in a vertical and horizontal direction may be attached to the resin plate, and the microplate may be collected by a mechanism that moves in the XY directions. By using a microplate, many components can be separated and collected, a system can be achieved, and it can be applied to combinatorial chemistry and the like.

[0011]

As described above, in the preparative LCMS according to the present invention, the collection container is provided at a position facing the spray unit, and the collection is performed while exchanging the container for each sample component. Sorting can be performed without wasting. Further, since the sample sprayed in the interface section is efficiently collected, the interface section becomes clean and the number of times of washing can be reduced.

[Brief description of the drawings]

FIG. 1 is a configuration diagram of a conventional preparative LCMS.

FIG. 2 is a configuration diagram of a preparative LCMS that is an embodiment of the present invention.

FIG. 3 is a configuration diagram of a microplate.

[Explanation of symbols]

 1: Column 5: Collection container 7: Interface section 7a: Spray section 8: Sampling hole 9: Detection section 10: Control section 11: Turntable

Claims (2)

[Claims] 1. A preparative liquid chromatograph mass spectrometer for separating a sample into components by a separation column in a liquid chromatograph unit, detecting the separated components by a mass spectrometric unit, and separating each component. A sample component eluted from is sprayed at atmospheric pressure, an interface unit that sends a part of the sample component to the mass spectrometry unit through the sampling hole, and a mass spectrometry unit that performs mass analysis of the sample that has passed through the sampling hole. A plurality of recovery means provided exchangeably at positions opposed to the spray direction in order to collect the sample components sprayed in the interface part, and a control part for replacing the recovery means by a signal from the mass analysis part. Preparative liquid chromatograph mass spectrometer. 2. The spraying means of the interface unit is directed downward, and a collection container is provided at a position opposed to the spraying means. The spraying means is located in a space between the spraying means and the collection means, and the spraying direction is horizontal. 2. The preparative liquid chromatograph mass spectrometer according to claim 1, wherein a sampling hole of the mass spectrometer is provided in the direction.