Patent Description:
A mass spectrometer is an analyzer that separates ions according to a mass-to-charge ratio by electrical and magnetic action and measures an abundance thereof. There are various separation methods such as a quadrupole type, a time-of-flight type, an ion trap type, or the like, and in any one of the methods, main purpose of using the analyzer is to perform qualitative analysis of a sample containing an unknown component or quantitative analysis of a sample with unknown concentration.

When the qualitative analysis is performed, a mass spectrum is acquired, in which a horizontal axis represents a mass-to-charge ratio and a vertical axis represents an ion intensity. A mass number of an unknown sample and a structure thereof are inferred from a pattern of an ion peak in the mass spectrum. When the quantitative analysis is performed, the ion intensity at the mass-to-charge ratio specific to a substance to be quantified is measured for several minutes. By performing this measurement, a mass chromatogram in which a horizontal axis represents time and a vertical axis represents an ion intensity is acquired. Concentration of the unknown sample is calculated by obtaining a ratio of an area of a chromatogram of the unknown sample to an area of a chromatogram of a sample with known concentration.

The mass spectrometer is often used in association with a chromatograph. The chromatograph is a device that separates a component in a mixture by using intensity of chemical or physical interaction. Examples of the chromatograph include a gas chromatograph in which a mobile phase is a gas, a liquid chromatograph in which the mobile phase is a liquid, or the like. Accuracy of the qualitative analysis and the quantitative analysis is improved by separating an impurity component from a sample with the chromatograph and then performing analysis on the sample with the mass spectrometer. When the chromatogram is used, an ion signal appears in a peak shape in the chromatogram of an analysis result of the mass spectrometer.

Here, in any one of the qualitative analysis and quantitative analysis, an important point for maintaining the measurement accuracy is a peak location of the ion signal in a horizontal axis direction in the mass spectrum. The peak location of the ion signal is determined by values of electrical and magnetic forces applied to the mass spectrometer. The values of these forces are susceptible to an influence of a change in temperature and humidity around a device. Therefore, the peak location of the ion signal changes depending on the change in the temperature and humidity therearound, which results in a difference from a true mass-to-charge ratio. When the difference therefrom is significantly large, the qualitative analysis cannot identify what a sample to be measured is. In the quantitative analysis, there is a problem that a peak of an ion signal of a substance to be measured in the chromatogram cannot be seen.

For the reasons described above, normally, before the mass spectrometer is used, a standard sample including the known mass number is measured to obtain the mass spectrum, and the horizontal axis of the mass spectrum is corrected based on the peak location of the ion signal. This operation is referred to as mass calibration or mass correction. In order to perform the mass calibration accurately, it is required to measure the ion signal of the standard sample for a certain period of time in a state where a sufficient amount of signals are maintained.

<CIT> (PTL <NUM>) <NUM> is a literature relating to such a mass calibration method. In this literature, an internal standard sample including the known mass number is mixed with a mobile phase solvent by using a liquid chromatograph feed pump. The internal standard sample is introduced into the mass spectrometer continuously or at a predetermined interval according to a pulse. Next, the mass spectrum derived from the internal standard sample can be referred to, and the mass calibration of the mass spectrum of a target component can be performed by an internal standard method.

<CIT> (PTL <NUM>) describes that the mass calibration is performed by continuously adding a predetermined amount of a standard substance, the exact mass-to-charge ratio value of which is known and which is clearly not contained in a target sample, to eluate.

The method described in <CIT> (PTL <NUM>) has a problem that, for example, the liquid chromatograph feed pump and a column become dirty and clogged by the standard sample such that the life of the column becomes shortened. The method described in <CIT> (PTL <NUM>) requires a unit for continuously adding the standard sample. In order to implement this unit, it is required to provide a new mechanism for controlling a continuous operation, such as a liquid feed pump which is different from the liquid feed pump of the mobile phase solvent of the liquid chromatograph. Therefore, there is a problem that introduction cost of a device is increased by an amount of a newly added unit. Furthermore, PTL <NUM> discloses liquid separation/mass spectrometry (LS/MS) apparatus, wherein an ion source of the mass spectrometer is in fluid communication with a switching valve that communicates effluent from a liquid separation system to the source when the switching valve is in a first position corresponding to the analytical mode of operation, and communicates one or more reference liquids from a calibrant system to the ion source when the switching valve is in a second position corresponding to the calibration mode of operation. Eventually, PTL <NUM> discloses a method for reducing or eliminating matrix interfering components in a biopharmaceutical product in a liquid chromatography-mass spectrometry system, wherein the entire flow of an eluant emerging from liquid chromatography of a sample, for a time period to remove contaminants that cause matrix interference to a degree sufficient to allow a desired accuracy in detection of an extractable is diverted to waste.

The present invention has been made in consideration of the above-described problems, and an object thereof is to provide a liquid chromatograph mass spectrometer that prevents contamination of a pump and a column and that can perform mass calibration without adding a complicated mechanism.

The above-mentioned problem is solved by providing a liquid chromatograph mass spectrometer as set out in the appended set of claims. Preferred embodiments of the present invention are described in the dependent claims.

According to the present invention, it is possible to provide a liquid chromatograph mass spectrometer that prevents contamination of a pump and a column caused by a standard sample and that can perform mass calibration without adding a complicated mechanism because the mass calibration can be performed by using a pump for feeding a mobile phase solvent of a liquid chromatograph.

Hereinafter, embodiments will be described with reference to the accompanying drawings. In the accompanying drawings, a functionally identical element may be represented by the same number or a corresponding number. While the accompanying drawings show embodiments and implementation examples based on a principle of the present disclosure, the drawings are provided for understanding of the present disclosure and are by no means used for limited interpretation of the present disclosure. Description of this specification is only a typical example, and does not limit the scope of the claims of the present disclosure or an application example thereof in any sense.

A configuration example of a liquid chromatograph mass spectrometer according to a first embodiment will be described with reference to a schematic diagram of <FIG>. A liquid chromatograph mass spectrometer <NUM> is roughly formed of a liquid chromatograph <NUM> including a liquid feed pump <NUM> for feeding a mobile phase solvent <NUM>, a mass spectrometer <NUM>, a standard sample container <NUM>, and a pipe <NUM>.

Although not shown in <FIG>, the liquid chromatograph <NUM> includes a column or the like in addition to the liquid feed pump <NUM>. The mass spectrometer <NUM> performs mass spectrometry of each component according to a component separated and introduced by the column by chromatography.

The pipe <NUM> allows the liquid chromatograph <NUM> and the mass spectrometer <NUM> to be connected to each other, and conveys a separated component of a measurement target sample from the liquid chromatograph <NUM> to the mass spectrometer <NUM>. The standard sample container <NUM> is provided in the middle of a path of the pipe <NUM>, and is disposed so as to be connectable in series with the liquid chromatograph <NUM> and the mass spectrometer <NUM>. The standard sample container <NUM> is a container in which a standard sample solution for mass calibration is filled.

The configuration of the standard sample container <NUM> will be described together with an operation thereof with reference to a cross-sectional view of <FIG> shows an initial state of the standard sample container <NUM>, and <FIG> show how a standard sample solution <NUM> stored inside the standard sample container <NUM> is pushed out.

The standard sample container <NUM> is roughly formed of a case <NUM> and a partition plate <NUM>. The case <NUM> has a cylindrical shape in which a flow path direction is a longitudinal direction, and includes an injection hole H1 in a first wall surface <NUM> at one end thereof and a discharge hole H2 in a second wall surface <NUM> at the other end thereof. The partition plate <NUM> partitions the inside of the case <NUM> having the cylindrical shape in a direction intersecting a flow path, and is further disposed so as to be movable in the flow path direction (a direction connecting the injection hole H1 and the discharge hole H2). That is, in the standard sample container <NUM>, the standard sample solution <NUM> is filled between the partition plate <NUM> and the second wall surface <NUM>, and the mobile phase solvent <NUM> is injected into a location between the first wall surface <NUM> and the partition plate <NUM>. As shown in <FIG>, the mobile phase solvent <NUM> is introduced from the injection hole H1 and the partition plate <NUM> is pushed, whereby the standard sample solution <NUM> is discharged from the discharge hole H2. A shape of the injection hole H1 and the discharge hole H2 can be, for example, about <NUM>/<NUM> inch (approx. <NUM>,<NUM>) in diameter, and can be formed in a shape to which a pipe tube and a screw of the liquid chromatograph can be connected.

The partition plate <NUM> is designed to move the inside of the case <NUM> in a direction from the injection hole H1 to the discharge hole H2 when a pressure of several tens of MPa is applied. For example, it is desirable that the standard sample solution <NUM> is a substance obtained in a manner that a substance in which a plurality of mass numbers of ion peaks appear, such as polypropylene glycol, cesium iodide, or the like, is dissolved in water and an organic solvent such as methanol/acetonitrile or the like. On the other hand, it is desirable that the mobile phase solvent <NUM> is water or the organic solvent such as methanol/acetonitrile or the like.

For example, a connector <NUM> as shown in a cross-sectional view of <FIG> is attached to the injection hole H1 and the discharge hole H2 of the standard sample container <NUM>. The connector <NUM> includes a seal plug <NUM>, a joint <NUM>, a screw <NUM>, and a tube <NUM>. The tube <NUM> is attached to the injection hole H1 or the discharge hole H2, and one end on a side of the seal plug <NUM> of the joint <NUM> is connected to the above-described pipe <NUM>.

The joint <NUM> is a cylindrical hollow member, and includes a hollow portion H3 along an axial direction of a cylinder. A screw hole is formed in an inner wall on one end side of the joint <NUM>, and the seal plug <NUM> is screwed thereinto. A similar screw hole is formed in an inner wall on the other end side of the joint <NUM>, and the screw <NUM> is screwed thereinto. The above-described pipe <NUM> is connected to one end of the joint <NUM> after the seal plug <NUM> is removed. Therefore, an inner diameter of one end of the joint <NUM> is configured to match an outer diameter of the pipe <NUM>.

The screw <NUM> includes a through hole H4 along a central axis thereof, and the tube <NUM> is inserted into the through hole H4. When the screw <NUM> into which the tube <NUM> is inserted is connected to the joint <NUM> and the tube <NUM> is further fixed to the injection hole H1, the connector <NUM> can be connected to the standard sample container <NUM>. In this manner, the standard sample container <NUM> can be connected to the pipe <NUM> by using the screw hole of the joint <NUM>.

When the standard sample container <NUM> is carried, the seal plug <NUM> is connected to one end of the joint <NUM>. The standard sample container <NUM> can be sealed with the seal plug <NUM> in a state where the inside of the standard sample container <NUM> is filled with the standard sample solution <NUM>. In related art, the standard sample solution is left in an opened state, or it is required to repeatedly open and close a lid of a sample container after opening the lid thereof once such that the standard sample solution easily deteriorates. On the other hand, when the standard sample container <NUM> and the connector <NUM> of the first embodiment are used, the standard sample solution in a single-use amount can be sealed and stored, such that the deterioration in the standard sample solution can be prevented.

Next, with reference to a timing chart of <FIG>, an operation related to the mass calibration in the liquid chromatograph mass spectrometer of <FIG> will be described. In the device of <FIG>, when the mass calibration is started, the standard sample container <NUM> is connected to the pipe <NUM> (time t1). When the standard sample container <NUM> is connected thereto, the discharge hole H2 is connected to the mass spectrometer <NUM> via the connector <NUM>, and the injection hole H1 is connected to the liquid feed pump <NUM> via the connector <NUM>. In the standard sample container <NUM> at the start of the mass calibration, the partition plate <NUM> moves to a side of the injection hole H1 as shown in <FIG>, and an internal space between the partition plate <NUM> and the discharge hole H2 is filled with the standard sample solution <NUM>.

After the standard sample container <NUM> is connected to the liquid feed pump <NUM> and the mass spectrometer <NUM> via the pipe <NUM>, liquid feed of the mobile phase solvent <NUM> from the liquid feed pump <NUM> starts. Since a pressure at the time of the liquid feed of the mobile phase solvent <NUM> is several tens of MPa, the partition plate <NUM> of the standard sample container <NUM> moves in the case <NUM> with the liquid feed thereof.

As the partition plate <NUM> moves, the standard sample solution <NUM> is pushed out of the discharge hole H2 and reaches the mass spectrometer <NUM> (refer to <FIG>). As shown in <FIG>, while the standard sample container <NUM> is connected and the standard sample solution <NUM> is pushed out by action of the liquid feed pump <NUM>, an ion signal of the standard sample solution <NUM> is detected with a constant intensity in the mass spectrometer <NUM>. The mass calibration can be performed by correcting a horizontal axis of a mass spectrum based on a peak location of the ion signal of the standard sample solution <NUM> in a mass spectrum measurement result.

As shown in <FIG>, when the partition plate <NUM> reaches the other end of the case <NUM>, the ion signal of the standard sample solution <NUM> is not observed in the mass spectrometer <NUM>. At this time, the case <NUM> is in a state of being filled with the mobile phase solvent <NUM>. When the ion signal of the standard sample solution <NUM> is not observed in the mass spectrometer <NUM>, the liquid feed pump <NUM> is stopped and the liquid feed of the mobile phase solvent <NUM> is stopped.

After that, the standard sample container <NUM> is removed from the pipe <NUM> (time t2 in <FIG>), and for example, the liquid feed pump <NUM> and the mass spectrometer <NUM> are directly connected to each other by the pipe <NUM>. When the mobile phase solvent <NUM> is fed again from the liquid feed pump <NUM> in this state, the standard sample solution <NUM> remaining in a flow path from the liquid feed pump <NUM> to the mass spectrometer <NUM> can be cleaned.

As described above, according to the configuration of the liquid chromatograph mass spectrometer of the first embodiment, as described in <CIT> (PTL <NUM>), the standard sample solution does not pass through the liquid feed pump <NUM> of the liquid chromatograph <NUM>. Therefore, it is possible to prevent the liquid feed pump <NUM> from being contaminated by the standard sample solution.

Since the liquid feed pump <NUM> of the liquid chromatograph <NUM> is used, the number of liquid feed pumps required to be operated as the liquid chromatograph mass spectrometer can be minimized.

Next, a liquid chromatograph mass spectrometer according to a second embodiment will be described with reference to <FIG> and <FIG>. <FIG> is a schematic diagram illustrating a configuration example of the liquid chromatograph mass spectrometer according to the second embodiment. In the liquid chromatograph mass spectrometer of the second embodiment, the liquid chromatograph <NUM> includes a column mounting portion <NUM> for mounting a column. In <FIG>, the same members as those of the first embodiment will be denoted by the same reference signs as those of <FIG>, and duplicated description thereof will be omitted below.

The column mounting portion <NUM> is configured to be capable of selectively mounting a column <NUM> which is used when liquid chromatograph mass spectrometry (LC/MS) is performed, and the standard sample container <NUM> which is used when the mass calibration is performed. The column <NUM> and the standard sample container <NUM> which are mounted on the column mounting portion <NUM> can be connected in series between the liquid feed pump <NUM> and the mass spectrometer <NUM> via the pipe <NUM>, when the column <NUM> and the standard sample container <NUM> are respectively used.

As the standard sample container <NUM>, the one shown in <FIG> can be adopted. However, a volume of the case <NUM> of the standard sample container <NUM> is the same as a volume of the column <NUM> or a volume that can be housed in the column mounting portion <NUM>. The column mounting portion <NUM> is usually kept at <NUM> to <NUM>. In order to cope with such an environment, the case <NUM> may use a heat insulating material. By using the heat insulating material, it is possible to prevent the standard sample solution <NUM> in the standard sample container <NUM> from deteriorating by heat.

Next, an operation of the liquid chromatograph mass spectrometer of <FIG> will be described with reference to a timing chart of <FIG> shows, as an example, a procedure in which the liquid chromatograph mass spectrometry (LC/MS), the mass calibration of the mass spectrometer <NUM>, and the cleaning of the flow path are performed in order.

When the liquid chromatograph mass spectrometry (LC/MS) is performed, the column <NUM> is connected to the column mounting portion <NUM> (time t11 in <FIG>). The column <NUM> is connected to the flow path from the liquid chromatograph <NUM> to the mass spectrometer <NUM> via the pipe <NUM>. When the column <NUM> is connected thereto, several to several tens of µL of a sample to be analyzed is injected by a pump (not shown) and adsorbed in the column <NUM>. Next, an appropriate mobile phase solvent is fed toward the column by the liquid feed pump <NUM>. Accordingly, the sample to be analyzed is eluted from the column <NUM> and sent out to the mass spectrometer <NUM>.

When the mass spectrometry is performed on the sample to be analyzed sent out therefrom with the mass spectrometer <NUM>, for example, an ion signal of a measurement substance in the sample appearing in the chromatogram appears in a peak shape having a width of several seconds at any timing between time t11 and t12.

When the liquid chromatograph mass spectrometry is completed, the mass calibration continuously starts. In this case, the column <NUM> is removed from the column mounting portion <NUM>, and the standard sample container <NUM> is connected thereto instead. A state of the ion signal at the time of the mass calibration, a processing method, and a state of the cross-sectional view of the standard sample container <NUM> are the same as those of the first embodiment.

When the partition plate <NUM> completely moves from the side of the injection hole H1 to the side of the discharge hole H2 inside the case <NUM>, the ion signal does not appear in the mass spectrometer <NUM>, such that the operation of the liquid feed pump <NUM> stops, and the liquid feed of the mobile phase solvent is completed. As described above, the mass calibration is completed.

When the mass calibration is completed, the process continuously proceeds to a flow path cleaning step. When the ion signal is not observed and the operation of the liquid feed pump <NUM> is stopped, continuously, the standard sample container <NUM> connected to the column mounting portion <NUM> is removed, and the column <NUM> is connected thereto instead. When the mobile phase solvent <NUM> is fed again from the liquid feed pump <NUM> in this state, the standard sample solution remaining in the flow path from the column mounting portion <NUM> to the mass spectrometer <NUM> can be cleaned. After cleaning the flow path, the sample is injected again and the liquid chromatograph mass spectrometry (LC/MS) is restarted in the same manner as described above.

As described above, in the device of the second embodiment, the column <NUM> is mounted on the column mounting portion <NUM> when the liquid chromatograph mass spectrometry (LC/MS) is performed, and when the mass calibration is performed, the standard sample container <NUM> is mounted on the column mounting portion <NUM> instead of the column <NUM>. Therefore, according to the device of the second embodiment, in addition to obtaining an effect described in the first embodiment, it is possible to prevent the column <NUM> for the liquid chromatograph mass spectrometry from being contaminated by the standard sample solution. It is also possible to eliminate a possibility that the column <NUM> is clogged such that the life of the column <NUM> is shortened.

Next, a liquid chromatograph mass spectrometer according to a third embodiment which is not claimed in the appended claims will be described with reference to <FIG> and <FIG>. An overall configuration of the device of the third embodiment may be the same as the overall configuration of the device of the second embodiment (<FIG>). However, in the third embodiment, a structure of the standard sample container <NUM> is different from that of the second embodiment.

<FIG> is a schematic diagram illustrating the structure of the standard sample container <NUM> that is not claimed. In <FIG> shows a state in which the standard sample container <NUM> does not start to be used, (b) shows a state indicating a middle stage in which the standard sample container <NUM> is being used, and (c) shows a state indicating a stage in which the use of the standard sample container <NUM> is completed.

As an example, this standard sample container <NUM> is formed of the case <NUM> and a tube <NUM> extending inside the case <NUM>, for example, in a spiral shape. The standard sample solution <NUM> is injected into the tube <NUM> at a stage before the mass calibration is performed. A diameter (a thickness) of the tube <NUM> is designed so that the standard sample solution <NUM> is not mixed with other solutions due to diffusion. A material of the tube <NUM> is selected so as to withstand several tens of MPa of pressure generated when the liquid feed is performed by the liquid chromatograph. As an example, characteristics of the tube <NUM> are an inner diameter of <NUM> to <NUM>, a length of <NUM> to <NUM>, and a PEEK tube as a material, and the tube <NUM> can be selected so that an inside thereof can be filled with tens to hundreds of µL of the standard sample solution <NUM>.

The tube <NUM> is formed in the spiral shape in order to be able to store the standard sample solution <NUM> in the amount required for performing the mass calibration. In <FIG>, a spiral is drawn so as to draw a large number of loops centered on a direction intersecting the flow path (a direction perpendicular to a paper surface), and the spiral shape is not limited to that shown in <FIG>. For example, a direction of the loop may be centered on a direction parallel to the flow path (a direction of the paper surface). Disposition itself of the spiral shape of the tube <NUM> is also an example, and is not limited to the spiral shape. For example, instead of having the spiral shape, the tube <NUM> may have at least one folded portion in the case <NUM>, such as a shape in which the tube <NUM> is disposed in a zigzag shape or the like.

The tube <NUM> is connected between the injection hole H1 and the discharge hole H2. The tube <NUM> is pulled out from the injection hole H1 and the discharge hole H2 and connected to the pipe <NUM>. The same connector <NUM> as that of the first embodiment may be disposed in the injection hole H1 and the discharge hole H2, and the tube <NUM> and the pipe <NUM> may be connected to each other via the connector <NUM>. However, even though the connector <NUM> is not provided by allowing the tube <NUM> to have an appropriate cross-sectional diameter and to be formed in the spiral shape, leakage of the standard sample solution <NUM> to an outside of the tube <NUM> is prevented.

The standard sample container <NUM> of the third embodiment is different from that of the first embodiment in that the partition plate <NUM> is not provided, and the standard sample solution <NUM> in the tube <NUM> receives direct pressure from the mobile phase solvent injected from one end of the tube <NUM> and is discharged from the other end thereof. The shape of the standard sample container <NUM> is substantially symmetrical, which is different from that of the first embodiment. Therefore, in the third embodiment, the structure of <FIG> may be reversed, the discharge hole H2 may be connected to a side of the liquid chromatograph <NUM>, and the injection hole H1 may be connected to a side of the mass spectrometer <NUM>. As will be described later, the cleaning of the flow path can also be performed while the standard sample container <NUM> is still connected to the flow path.

Next, an operation of the liquid chromatograph mass spectrometer of <FIG> will be described with reference to a timing chart of <FIG> shows, as an example, a procedure in which the liquid chromatograph mass spectrometry (LC/MS), the mass calibration of the mass spectrometer <NUM>, the cleaning of the flow path, and a Flow Injection Analysis (FIA) method are performed in order.

Since the liquid chromatograph mass spectrometry (LC/MS) can be performed in almost the same manner as that of the second embodiment (<FIG>), duplicate description thereof will be omitted. The mass calibration to be performed next is also performed by allowing the standard sample container <NUM> to be connected to the column mounting portion <NUM>, in the same manner as that of the second embodiment. The connection method is also the same as that of the second embodiment.

When the mass calibration is performed, the standard sample container <NUM> is connected to the column mounting portion <NUM> and connected to the pipe <NUM>, and then the mobile phase solvent <NUM> is fed from the liquid feed pump <NUM> toward the standard sample container <NUM>. Next, as shown in <FIG>, the mobile phase solvent <NUM> pushes the standard sample solution <NUM> in the tube <NUM> out toward the discharge hole H2, and the standard sample solution <NUM> flows toward the mass spectrometer <NUM>.

On the assumption that a flow rate is several to several tens of µL / min, the mass spectrometer <NUM> can observe the ion signal of the standard sample solution for about <NUM> minutes (time t22 to t23) with a stable intensity. A measurement result of the standard sample solution <NUM> is displayed as a mass spectrum on a display device (not shown) of the mass spectrometer <NUM>, and the mass calibration can be performed by correcting the horizontal axis of the mass spectrum based on this ion peak location.

When the mass calibration is completed, the process proceeds to the flow path cleaning step in the same manner as that of the second embodiment. However, in the third embodiment, after the mass calibration is completed, in a state where the standard sample container <NUM> is still mounted on the column mounting portion <NUM>, the cleaning step can be performed by using the tube <NUM> as the flow path. In this point, the second embodiment is different from the third embodiment in that after the mass calibration is completed, the standard sample container <NUM> is replaced with the column <NUM> and the cleaning step is performed. The standard sample container <NUM> of the third embodiment is different from the standard sample container <NUM> of the first embodiment in that the partition plate <NUM> is not provided, and even after the standard sample solution <NUM> is discharged, the flow path of the tube <NUM> is open, and an inside of the tube <NUM> is filled with the mobile phase solution. Therefore, the cleaning of the flow path can be performed by continuously using the standard sample container <NUM> without replacing the standard sample container <NUM> with the column <NUM>.

When the cleaning step is completed, any sample can be continuously analyzed by the Flow Injection Analysis (FIA) method using the tube <NUM> of the standard sample container <NUM>. The FIA method is a method for performing the liquid chromatograph mass spectrometry without performing component separation by the column <NUM>. Since the measurement can be performed quickly without using the column <NUM>, a parameter of the measurement of the liquid chromatograph mass spectrometry can be optimized.

In the analysis by the FIA method, in a state where the standard sample container <NUM> is connected to the column mounting portion <NUM>, several to several tens of µL of any sample is injected while the appropriate mobile phase solvent is fed from the liquid feed pump <NUM>. Since the sample to be analyzed is slightly diffused until the sample to be analyzed reaches the mass spectrometer <NUM>, a peak width of the ion signal in the chromatogram is slightly wider than that of a case where the sample to be analyzed passes through the column <NUM>. After the analysis by the FIA method is completed, the standard sample container <NUM> is removed from the column mounting portion <NUM>, the column <NUM> is connected thereto instead, and the liquid chromatograph mass spectrometry is performed again.

As described above, according to the standard sample container <NUM> of the third embodiment, since the tube <NUM> of the standard sample container <NUM> can be continuously used as the flow path to be cleaned after the mass calibration is completed, a deterioration level of the column <NUM> can be reduced as compared with the above-described embodiment in which the cleaning is performed through the column <NUM>.

Next, a liquid chromatograph mass spectrometer according to a fourth embodiment which is not claimed in the appended claims. will be described with reference to <FIG> and <FIG>. An overall configuration of the device of the fourth embodiment may be the same as the overall configuration of the device of the second embodiment (<FIG>). However, a structure of the standard sample container <NUM> of the fourth embodiment is different from that of the second embodiment.

<FIG> is a schematic diagram illustrating the structure of the standard sample container <NUM> that is not claimed. The standard sample container <NUM> is formed of the case <NUM> and a filler <NUM> that is filled in the case <NUM> and can absorb the standard sample solution <NUM>. The filler <NUM> is filled in a cavity of the case <NUM>. The injection hole H1 and the discharge hole H2 provided at opposite ends of the case <NUM> can be configured to be connectable to the same connector (<FIG>) as that of the above-described embodiment.

A material of the filler <NUM> may be the same as that of a filler to be filled in the column <NUM>, such as silica gel or the like. However, the standard sample container <NUM> in the fourth embodiment is dedicated to the mass calibration, and is a container different from the column <NUM> to be used for the liquid chromatograph mass spectrometry.

Next, an operation of the liquid chromatograph mass spectrometer of <FIG> will be described with reference to a timing chart of <FIG> shows, as an example, a procedure in which the liquid chromatograph mass spectrometry (LC/MS), the mass calibration of the mass spectrometer <NUM>, and the cleaning of the flow path are performed in order. During the liquid chromatograph mass spectrometry (LC/MS), the mass calibration, and the cleaning of the flow path, a connection state of the column <NUM> and the standard sample container <NUM> to the column mounting portion <NUM>, and a sample injection operation are the same as those of the third embodiment. Therefore, duplicate description thereof will be omitted below. However, the ion signal obtained during the mass calibration is different from that of the third embodiment, and becomes a chromatogram with a peak shape such as a mountain having a wide width.

In the fourth embodiment, the standard sample container <NUM> includes the filler <NUM> at the inside thereof, and the standard sample solution <NUM> is housed at the inside of the standard sample container <NUM> in a form of being absorbed by the filler <NUM>. Since the filler <NUM> has high absorbency, the standard sample solution <NUM> of contents does not leak even in a state where the seal plug <NUM> of the connector <NUM> is loose. Therefore, the work of connecting the standard sample container <NUM> to the column mounting portion <NUM> becomes easier than that of the above-described embodiments.

Continuously, a liquid chromatograph mass spectrometer according to a fifth embodiment will be described with reference to <FIG> and <FIG>. <FIG> is a schematic diagram illustrating a structure of the liquid chromatograph mass spectrometer according to the fifth embodiment. In the device of the fifth embodiment, the column mounting portion <NUM> is configured to be capable of mounting the column <NUM> for the liquid chromatograph mass spectrometry and the standard sample container <NUM> for the mass calibration in parallel to each other at the same time.

A valve 111a is provided between the liquid feed pump <NUM> and the column mounting portion <NUM> so that the column <NUM> and the standard sample container <NUM> can be selectively used. A valve 111b is provided between the column mounting portion <NUM> and the mass spectrometer <NUM>. The column <NUM> and the standard sample container <NUM> are connected in parallel between the valve 111a and the valve 111b. A solution flowing through the column <NUM> or the standard sample container <NUM> is introduced into the mass spectrometer <NUM> via the valve 111b. The valves 111a and 111b are configured to selectively connect either one of the column <NUM> and the standard sample container <NUM> to the flow path. A plurality of columns <NUM> and a plurality of standard sample containers <NUM> may be connected to one column mounting portion <NUM>.

Next, an operation of the liquid chromatograph mass spectrometer of <FIG> will be described with reference to a timing chart of <FIG> shows, as an example, a procedure in which the liquid chromatograph mass spectrometry (LC/MS), the mass calibration of the mass spectrometer <NUM>, the cleaning of the flow path, and the Flow Injection Analysis (FIA) method are performed in order.

Since the liquid chromatograph mass spectrometry (time t41 to t42 in <FIG>) can be performed in almost the same manner as that of the second embodiment (<FIG>), duplicate description thereof will be omitted. The mass calibration (time t42 to t43) to be performed next is also performed by connecting the standard sample container <NUM> to the column mounting portion <NUM>, in the same manner as that of the second embodiment. However, in an operation example of <FIG>, the column <NUM> is in a state of being always connected (mounted on) to the column mounting portion <NUM> even when the mass calibration is performed. The standard sample container <NUM> is also in a state of being always connected to the column mounting portion <NUM> when the column <NUM> is used. However, when the mass calibration starts (for example, time t42), the new standard sample container <NUM> filled with the standard sample is replaced with the old standard sample container <NUM> that is already used. As described above, both the column <NUM> and the standard sample container <NUM> are always mounted on the column mounting portion <NUM>, and only one of the column <NUM> and the standard sample container <NUM> is selectively connected to the valves 111a and 111b. Since the cleaning and the operation in the FIA are almost the same as those of the third embodiment, duplicate description thereof will be omitted.

As described above, in the fifth embodiment, the column mounting portion <NUM> can be maintained in a state where the column <NUM> and the standard sample container <NUM> are provided in parallel to each other and are simultaneously mounted on the column mounting portion <NUM>. Since the column <NUM> can be left connected to the column mounting portion <NUM>, the column <NUM> can always be maintained in a warm state in the column mounting portion <NUM>.

Continuously, a liquid chromatograph mass spectrometer according to a sixth embodiment will be described with reference to <FIG> is a schematic diagram illustrating a structure of the liquid chromatograph mass spectrometer according to the sixth embodiment. In the device of the sixth embodiment, in the same manner as that of the fifth embodiment, the column mounting unit <NUM> is configured to be capable of mounting the column for the liquid chromatograph mass spectrometry and the standard sample container for the mass calibration in parallel at the same time. In the sixth embodiment, a plurality of standard sample containers 14a and 14b can be mounted on one column mounting portion <NUM>.

Claim 1:
A liquid chromatograph mass spectrometer, comprising:
a liquid chromatograph (<NUM>) including a liquid feed pump (<NUM>) configured to feed a mobile phase solvent (<NUM>) toward a standard sample container (<NUM>); and
a mass spectrometer (<NUM>) configured to analyze a mass of a sample; wherein
the standard sample container (<NUM>) configured to be installed between the liquid feed pump (<NUM>) of the liquid chromatograph (<NUM>) and the mass spectrometer (<NUM>), wherein the standard sample container (<NUM>) is configured to be connected in series with the liquid chromatograph (<NUM>) and the mass spectrometer (<NUM>), and to house a standard sample for mass calibration,
characterized in that:
the standard sample container (<NUM>) includes:
a cylindrical case that includes an injection hole (H1) at a first end and a discharge hole (H2) at a second end and that has a flow path direction as a longitudinal direction, and
a partition plate (<NUM>) configured to be movable along an inner wall of the case (<NUM>) and partitioning an inside of the case (<NUM>), and wherein
the partition plate (<NUM>) is configured to be movable in a direction of the discharge hole (H2) due to movement of a mobile phase solution from the injection hole (H1).