JP4566800B2 - Mass spectrometer - Google Patents

Description

  The present invention relates to a mass spectrometer, and more particularly to a mass spectrometer that measures a liquid sample.

  As an apparatus for measuring a liquid sample with a mass spectrometer, there is a liquid chromatogram mass spectrometer (LC-MS) composed of a solvent, a pump for feeding it, an autosampler for injecting the liquid sample, and a mass spectrometer. In this LC-MS, a liquid sample is injected from an autosampler, introduced into a solvent sent by a pump, sent to a mass spectrometer, and measured.

  At this time, when the solvent or liquid sample reaches the mass spectrometer, it is vaporized and ionized by a high temperature of 200 to 300 ° C. and an applied voltage of 2 to 3 KV.

  In this LC-MS, when performing continuous mass analysis, first, the autosampler is made to recognize the location of the vial prepared in advance and the injection amount so that the sample is injected by the number of times determined by the user. . The controller for controlling the mass spectrometer is made to recognize the same number of measurements.

  The autosampler and the mass spectrometer communicate with each other via a control device that controls each of them, and the autosampler receives a liquid sample injection command signal from the mass spectrometer and injects the liquid sample. The autosampler also sends a measurement start signal to the mass spectrometer after injecting the sample. When the measurement is completed, the mass spectrometer sends a command signal for the next sample injection to the autosampler, the autosampler receives the liquid sample injection command signal from the mass spectrometer and injects the liquid sample, and the autosampler Then, a signal for starting measurement is sent to the mass spectrometer. Continuous automatic analysis can be performed by repeating this cycle.

  In the LC-MS, the concentration of the separated and purified components is detected by a UV detector before being introduced into the splitter (arranged before the mass spectrometer), and sent from the splitter to the mass spectrometer according to the detected concentration. Patent Document 1 discloses a technique for changing the liquid amount.

  The technique described in Patent Document 1 is a technique for performing analysis under optimum conditions from a high concentration to a low concentration sample.

JP 2002-116193 A

  By the way, when measuring a liquid sample, a sample whose concentration is unknown is often measured in advance. In this case, if a sample having a high concentration is sent to the mass spectrometer and the measurement of the sample is continuously performed, the mass spectrometer may be contaminated. If the mass spectrometer is contaminated, the detection sensitivity of the measurement is lowered and accurate measurement cannot be performed.

  In addition, in the case of a sample whose concentration is unknown, since the optimal concentration for mass spectrometry is unknown, it was necessary to prepare a sample diluted with multiple types of dilution rates. For this reason, consumption of precious samples has increased.

  Therefore, it is conceivable to apply the technique described in Patent Document 1, but the determination of the concentration level up to whether or not the mass spectrometer is contaminated is made by the detection output signal of the UV detector provided in the preceding stage of the splitter. It is not possible.

  An object of the present invention is to realize a mass spectrometer capable of suppressing the occurrence of contamination of the mass spectrometer and preventing a decrease in detection sensitivity when measuring a liquid sample of unknown concentration in the mass spectrometer. It is.

  The outline of the function for determining the concentration of the liquid sample, which is a means for solving the problem, will be described below.

  In the present invention, the intensity of the measured peak is used as a reference for determining the concentration by the mass spectrometer. The user of the mass spectrometer determines a peak value (assumed to be M) that the sample concentration should be judged to be too high when a peak equal to or higher than a preset value is generated, and causes the mass spectrometer to recognize this value. If a peak exceeding M appears during measurement, the mass spectrometer determines that the concentration of the sample is high, stops the voltage supply to the ionization means, and does not ionize the sample solution. The mass spectrometer sends a signal to the autosampler to prepare a low concentration sample.

  In addition, the user of the mass spectrometer causes the mass spectrometer to recognize the peak value (m) that is determined that the concentration of the sample is low when the measured peak does not exceed other set values. If the number of peaks exceeding this set value in the measurement result is small, the mass spectrometer determines that the sample concentration is low, and the mass spectrometer should prepare a sample with a concentration higher than the sample concentration prepared during the previous measurement. Send a signal to the autosampler. If the peak value is less than or equal to M and the number of m peaks is greater than or equal to a certain value, it is determined that the concentration of the measurement sample at that time is appropriate, and the measurement of the sample is terminated.

  According to the present invention, when measuring a liquid sample of unknown concentration, it is possible to suppress the occurrence of contamination of the mass spectrometer and to prevent a decrease in detection sensitivity. In addition, an increase in sample consumption can be prevented.

  Hereinafter, an embodiment of the present invention will be described with reference to the drawings.

  FIG. 1 is a schematic configuration diagram of a mass spectrometer according to an embodiment of the present invention.

  In FIG. 1, a mass spectrometer includes a pump 1 that sends out a solvent 3, an autosampler 2 that injects a liquid sample, a mass spectrometer 4, a controller 5 that controls the pump 1 and the autosampler 2, and mass spectrometry. And a control device 6 for controlling the total 4.

  The mass spectrometer which is one embodiment of the present invention is a so-called liquid chromatograph mass spectrometer (LC-MS). In FIG. 1, the solid line indicates the flow of the solution or liquid sample, and the dotted line indicates the flow of data or instruction signal.

  FIG. 2 is an explanatory diagram of the operation of the autosampler 2 in one embodiment of the present invention.

  In FIG. 2, the autosampler 2 includes a syringe 7, a cooler stacker 8, a sample diluent discharge port 10, a syringe cleaning solution discharge port 11, and a valve 12 having a sample injection port.

  The cooler stacker 8 can store a plurality of vial tubes 13 containing a sample therein.

  The syringe 7 is movably installed to any one of a vial tube 13, a sample diluent discharge port 10, a syringe cleaning solution discharge port 11, and a valve 12 having a sample injection port housed in a cooler stacker 8. .

Next, the operation of one embodiment of the present invention will be described.
FIG. 3 is a flowchart showing processing in the mass spectrometer according to the embodiment of the present invention.
In FIG. 3, the user first causes the autosampler 2 to recognize the dilution rate of the measurement sample (step S301).

FIG. 4 is a table showing the ratio of the stock solution to the diluted solution.
The user causes the autosampler 2 to recognize the dilution rate of the measurement sample based on the table shown in FIG. Subsequently, the first sample concentration is set from any of the concentrations shown in this table. As the first sample concentration, a value in the middle of the table shown in FIG. 4 is set.

  Next, settings are also made for the mass spectrometer 4. The user inputs the reference peaks M and m and the peak number n (step S301).

  The reference peaks M and m and the number of peaks n will be described later.

  Next, proceeding to step S302, the autosampler 2 adjusts the sample according to the sample concentration in the table shown in FIG.

  Specifically, the syringe 7 of the autosampler 2 is moved to the vial tube 13 containing the sample stock solution stored in the cooler stacker 8, and an amount of the sample set by the user is injected into the syringe 7 to obtain a new one. Inject into the vial tube 13. Subsequently, the dilute solution is injected into the syringe 7 from the sample diluting solution discharge port 10, injected into a new vial tube 13 into which the sample stock solution has been injected, and this suction / discharge operation is repeated to bring the sample to the designated sample concentration. adjust.

  Then, the autosampler 2 injects the prepared sample concentration sample into the sample injection port of the valve 12, and sends a measurement start instruction signal to the mass spectrometer 4 (step S302).

  Next, the mass spectrometer 4 receives the measurement start instruction signal from the autosampler 2 and starts measurement (step S303). Next, it is determined whether there is a peak exceeding the reference peak M during measurement (step S304).

FIG. 5 is a chromatographic diagram showing a case where a peak having an intensity higher than the reference peak M is measured during measurement by the mass spectrometer 4.
As shown in FIG. 5, when at least one peak having an intensity higher than the reference peak M is measured, the mass spectrometer 4 stops the voltage supply to the ionization means until the measurement time of this time elapses. , Stop ionization. This is to suppress contamination of the mass spectrometer 4. Then, after completion of the measurement, an instruction to prepare a sample having a concentration one step lower than the sample of the previous measurement is sent to the autosampler 2 (step S305).

  Next, the autosampler 2 sets a one-step low concentration sample concentration according to the table shown in FIG. 4 in accordance with the instruction from the mass spectrometer 4 (step S308).

  Next, it is determined whether or not the newly set sample concentration is already executed (step S309). If the sample concentration instructed at this time is a sample concentration that has already been executed, the process proceeds to step S310. If not, the process returns to step S302 to perform remeasurement.

  When an already executed sample concentration is instructed, the autosampler 2 displays an alarm message and prompts the user to review the sample concentration setting instructed (step S310).

  In step S305, when no peak equal to or greater than M appears, the mass spectrometer 4 determines based on whether or not there are n peaks greater than or equal to the reference peak m (step S306).

  FIG. 6 is a chromatogram diagram showing a case where seven peaks with an intensity greater than or equal to the reference peak m are measured during the measurement by the mass spectrometer 4, and FIG. 7 is the reference peak m or more during the measurement by the mass spectrometer 4. It is a chromatogram figure which shows the case where n or more peaks of intensity | strength are not measured.

  As shown in FIG. 6, when there are n peaks that are equal to or greater than the reference peak m, the measurement is considered good and the measurement is terminated (step S311).

  In addition, as shown in FIG. 7, when n or more peaks are not measured, it is determined that the concentration of the sample is low, and an instruction to prepare a sample having another higher concentration is sent to the autosampler 2 ( Step S307). The density stage in step S307 is narrower than the density stage in step S305. Then, the process proceeds to step S308. In FIG. 7, the mass spectrometer 4 recognizes the peak derived from the solvent in advance, and does not select the peak derived from the solvent as a criterion.

  The above measurement is repeated until a satisfactory result is obtained for a liquid sample whose concentration is unknown, or the setting of the sample concentration input to the autosampler 2 before measurement can be measured within a range that does not contaminate the mass spectrometer 4.

  Here, the reference peaks M and m and the number of peaks n will be described.

  The mass spectrometer 4 recognizes the mass per monovalent charge of a certain ionized molecule, and outputs measurement data with the amount as the peak intensity. The intensity of the peak varies depending on the concentration of the sample to be measured. When the concentration of the sample to be measured is high, the intensity of the peak is high, and when the concentration is low, the intensity of the peak is low. Further, the relationship between the concentration of the sample and the intensity of the peak is substantially proportional in the range where the peak intensity of the mass spectrometer can be detected.

  However, depending on the ease of ionization of the sample, the change in the intensity of the peak that changes with the change in the concentration of the sample changes. That is, in the case of a sample that is easily ionized, the peak intensity change that changes with the change in the concentration of the sample is large, and in the case of a sample that is difficult to ionize, the peak intensity change that changes with the concentration change tends to be small. For this reason, the concentration of the sample cannot be measured only by the peak intensity.

  On the other hand, when measuring a liquid sample, the mass spectrometer 4 may measure a sample whose concentration is unknown in advance. In this case, a high concentration sample is introduced into the mass spectrometer and measurement is continued for a long time. Then, the mass spectrometer 4 may be contaminated. When the mass spectrometer 4 is contaminated, the detection sensitivity of the measurement is lowered and accurate measurement cannot be performed. In this case, the mass spectrometer 4 needs to be specially cleaned.

  Therefore, the reference peak M is set in the mass spectrometer 4 before the measurement is started, and when the peak concentration higher than the reference peak M is measured, the voltage supply of the ionization means is immediately stopped to stop the ionization. To do. Thereby, the introduction of the sample into the mass spectrometer 4 can be stopped, and contamination of the mass spectrometer 4 can be suppressed. And it can measure with an appropriate density | concentration by making a sample density | concentration low and measuring again.

  On the other hand, when the sample concentration is low, the measurement result may not be clear enough to determine the measurement result.

  In this case, the reference peak m is set in the mass spectrometer 4 before the measurement is started, and when the peak intensity is lower than the reference peak m, it is determined that the sample concentration is low and the sample concentration is increased. Thus, measurement can be performed at an appropriate concentration.

  By setting the number n of peaks equal to or higher than the reference peak m before starting measurement and determining that the number of peaks equal to or higher than the reference peak m has reached n, it can be determined that a satisfactory concentration has been reached.

  In addition, it is possible to set a more accurate sample concentration by recognizing a peak derived from a specific solvent in advance and not selecting the peak derived from the specific solvent as a criterion.

  In one embodiment of the present invention, a value about 1000 times the background is set for the reference peak M, and a value about 10 times the background is set for the reference peak m.

  According to one embodiment of the present invention configured as described above, a mass spectrometer capable of analyzing a liquid sample of unknown concentration without contaminating the mass spectrometer 4 and without using a large amount of sample is realized. can do.

  Furthermore, when the autosampler 2 is instructed to select a sample concentration that has already been executed, an alarm message is displayed to the user, preventing repeated measurements with the same sample concentration, and wasteful sample consumption. And the measurement time can be shortened.

  It is also possible to display the sample dilution rate history data by the display means.

It is a schematic block diagram of the mass spectrometer by one Embodiment of this invention. Operation explanatory diagram of an autosampler in one embodiment of the present invention It is a flowchart which shows the process of the mass spectrometer by one Embodiment of this invention. It is a table | surface which shows the quantity of the stock solution set to an autosampler, and the ratio of a diluted solution It is a chromatograph figure showing the case where the peak of intensity more than the standard peak M is measured in the measurement result of the mass spectrometer by one embodiment of the present invention. In the measurement result of the mass spectrometer by one Embodiment of this invention, it is a chromatograph figure which shows the case where seven peaks of intensity | strength more than the reference | standard peak m are measured. In the measurement result of the mass spectrometer by one Embodiment of this invention, it is a chromatograph figure which shows the case where n or more peaks of the intensity | strength more than the reference | standard peak m are not measured.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 Pump 2 Autosampler 3 Solvent 4 Mass spectrometer 5 Control apparatus 6 Control apparatus 7 Syringe 8 Cooler stacker 10 Sample dilution liquid discharge port 11 Syringe washing liquid discharge port 12 Valve with sample injection port 13 Vial tube

Claims (3)

Mass spectrometer equipped with pump for delivering solvent, sample introduction means for introducing sample into solvent delivered from this pump, and mass spectrometer for performing mass analysis of sample introduced into solvent by this sample introduction means in,
If the measurement results of the above SL mass spectrometer is a peak exceeding the first criterion, the first concentration variation, and reduce the concentration of the sample, the peak appearing in the measurement result of the mass spectrometry is the When the concentration of the sample is reduced by the first concentration change range until the value becomes less than 1 criterion, and the peak appearing in the measurement result of the mass spectrometer becomes less than the first criterion, the measurement result is It is determined whether or not the number of peaks that exceed the second criterion, which is lower than the first criterion, among the peaks that appear is less than a predetermined number. Control means for controlling the sample introduction means so as to adjust the concentration of the sample supplied to the mass spectrometer by increasing the concentration of the sample by a second concentration change width smaller than the concentration change width. A mass spectrometer characterized by the above.   2. The mass spectrometer according to claim 1, wherein the sample introduction means does not readjust the sample concentration once adjusted for the same sample.   3. The mass spectrometer according to claim 2, wherein the sample introduction means displays a warning when the same sample is instructed to readjust the sample concentration once adjusted. apparatus.

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