Patent Application
20250146985
The present disclosure relates to a method for controlling a mass spectrometer.
A mobile phase solvent used in measurement by a liquid chromatograph mass spectrometer (LC/MS) contacts a solvent bottle, a tube group and a filter group of a synthetic resin system, and so on. A substance attached to a constituent of the solvent bottle, the tube group, and the filter group and the surface of them is gradually solved in the mobile phase solvent as the time elapses, and possibly becomes a foreign substance contaminating the mobile phase solvent. When the mobile phase solvent is contaminated by a foreign substance, a phenomenon that ionization of a measurement object substance intrinsically desired to be ionized is suppressed (ion suppression) occurs, and the measurement sensitivity of the measurement object substance deteriorates.
In Patent Literature 1 described below, measurement is performed adding an internal standard substance to a mobile phase solvent, and when the intensity of the internal standard substance becomes less than a reference, it is determined that the ion suppression has occurred (refer to the abstract).
In a prior art of adding an internal standard substance as described in Patent Literature 1, the internal standard substance itself possibly becomes a foreign substance contaminating the mobile phase solvent. Therefore, such technology is required that can detect contamination of a mobile phase solvent without adding a substance that possibly becomes a foreign substance.
The present disclosure has been made in view of such technical problems as described above, and its object is to provide a method for controlling a liquid chromatograph mass spectrometer by which contamination of a mobile phase solvent caused by a foreign substance can be detected without using an internal standard substance.
The method for controlling a liquid chromatograph mass spectrometer related to the present disclosure includes: calculating a first ratio of signal intensities at a first time point and a second time point when measurement is performed using a first mobile phase solvent; calculating a second ratio of signal intensities at the first time point and the second time point when measurement is further performed using a second mobile phase solvent; and determining whether or not the second mobile phase solvent is contaminated according to an absolute difference between the first ratio and the second ratio.
According to the method for controlling a liquid chromatograph mass spectrometer related to the present disclosure, contamination of a mobile phase solvent caused by a foreign substance can be detected without using an internal standard substance. Problems, configurations, and effects other than those described above will be clarified by explanation of embodiments described below.
Although ions generated by the ion source have various masses, AC voltage (HF voltage) and DC voltage allowing a target ion to pass through are applied to a first quadrupole electrode portion 540 (there is a quadrupole electrode 530 in the inside) by a quadrupole power supply 580, and only the target ion derived from the measurement sample is made to selectively pass through. To a second quadrupole electrode portion 541, a collision gas 570 (nitrogen gas, argon gas, and the like) for dissociating the target ion is introduced from a supply source through a gas line 571.
A second quadrupole electrode 531 normally applies only AC voltage from a quadrupole power supply 580 to eliminate mass selectivity, allows the target ion having passed through the first quadrupole electrode portion 540 and the gas to collide on each other, and thereby generates a fragment ion. The fragment ion having been generated passes through the second quadrupole electrode portion 541, and enters a third quadrupole electrode portion 542.
When HF voltage and DC voltage allowing the target fragment ion to pass through are applied to a third quadrupole electrode 532 by the quadrupole power supply 580, only the target fragment ion passes through the third quadrupole electrode portion 542. The target fragment ion having passed through is detected by a detector 550. A detection signal is sent to a data processing unit 560 (controller), and mass spectrometry is performed by the data processing unit 560.
Although a device aspect of a triple quadrupole type mass spectrometer called a Triple QMS was shown here as an example, the technology of the present disclosure can be applied also to a Single QMS quadrupole mass spectrometer where one unit of the QMF is arranged in the inside. Further, according to the embodiment, although explanation will be made with an example of the quadrupole as the mass filter, the technology of the present disclosure can be applied to a mass filter of not only the quadrupole but also of the multiple pole.
First, the mass spectrometer 5 measures the ion signal intensity using the first mobile phase solvent. The first mobile phase solvent is a mobile phase solvent not contaminated. Followings for example can be used as the first mobile phase solvent: (a) a mobile phase solvent not long after preparation; (b) a mobile phase solvent having been stored under a condition where the temperature and the humidity were managed after preparation until the time of use (refrigerator and the like). With the time point of starting elution using the first mobile phase solvent being made the time point 0, the mass spectrometer 5 measures the ion signal intensity I1, t1 at the time point t1 and the ion signal intensity I1, t2 at the time point t2 respectively. The time point t1 and the time point t2 are made the temporal points where the composition ratio (the liquid B ratio in
Next, the mass spectrometer 5 measures the ion signal intensity using the second mobile phase solvent. The second mobile phase solvent is a determination object for determining whether or not there is contamination. The second mobile phase solvent is a mobile phase solvent that is not the first mobile phase solvent at least, and includes for example such first mobile phase solvent that the time elapses after being arranged in the mass spectrometer 5. With the time point of starting elution using the second mobile phase solvent being made the time point 0, the mass spectrometer 5 measures respectively the ion signal intensity I2, t1 and I2, t2 at the time t1 and t2 which are same to those for the first mobile phase solvent. The mass spectrometer 5 calculates the ratio R2 of each ion signal intensity as follows: I2, t2/I2, t1=R2.
When the second mobile phase solvent is contaminated and contains the foreign substance much, it is considered that the ion signal intensity rises more than the time of non-contamination accompanying rise of the liquid B ratio by the effect. Utilizing the effect, by comparison of R1 and R2, it is possible to determine whether or not the second mobile phase solvent is contaminated. In concrete terms, when R2/R1 or R2−R1 is a threshold or more (namely when the both deviate from each other largely and the absolute difference of the both is a threshold or more), it is determined that the mobile phase solvent used in measurement of R2 is contaminated.
According to the temporal change of the liquid B ratio (namely the degree of the gradient in the gradient method) and the characteristic of the mobile phase solvent, and so on, it is possible that the rise rate of the ion signal intensity is smaller when the second mobile phase solvent is contaminated (namely R2<R1). Even in this case, similar determination can be performed by whether or not R1/R2 or R1−R2 is a threshold or more.
Since the magnitude relationship of R1 and R2 at the time of contamination can be grasped beforehand according to the kind of the mobile phase solvent, and so on, it is also possible to grasp beforehand which calculation expression of (a) R2/R1 or R2−R1 and (b) R1/R2 or R1−R2 should be used. When it is not clear which of R1 and R2 is bigger due to some circumstances, similar determination may be performed by whether or not the absolute difference |R2−R1| is a threshold or more.
It is preferable that the time point t1 and the time point t2 are to be set so as to avoid a time assumed as the elution time of an object substance measured by the mass spectrometer 5. The reason is that, although measurement of
A method for performing the measurement shown in
S301 can be performed for example when a user interface (for example a button on the device, an operation component on a screen interface, and so on) provided in the mass spectrometer 5 is operated. S302 can be performed when the user wants to determine contamination of the second mobile phase solvent. For example, S302 and onward may be performed while an object substance is measured, or S302 only (S303 and onward according to the necessity) may be performed independently in a vacant time when an object substance is not measured.
In step S303, the mass spectrometer 5 determines whether or not the second mobile phase solvent is contaminated based on the comparison result of R1 and R2. When the second mobile phase solvent is not contaminated, an analysis object sample is measured (S304). When the second mobile phase solvent is contaminated, the user is notified of the effect, and measurement of the analysis object sample is canceled (S305).
There is a case that plural sets of combinations of a container storing the liquid A and a container storing the liquid B are connected to the mass spectrometer 5 through a valve. For example, there is such case as illustrated in the first example of
When the mass spectrometer 5 is provided with a mechanism for replacing the mobile phase solvent within the container, the second mobile phase solvent within the container may be replaced by another mobile phase solvent using the mechanism. In the example illustrated in
It is also possible to switch the second mobile phase solvent to another mobile phase solvent, to measure thereafter the ion signal intensity and to calculate R2 at the time points t1 and t2 again with respect to the mobile phase solvent, and to determine contamination of the second mobile phase solvent again. Further, when the mobile phase solvent after switching is fresh and equivalent to the first mobile phase solvent, it is also possible to deem that the first mobile phase solvent has been re-introduced, to measure the ion signal intensity and to recalculate R1 at the time points t1 and t2 again.
The mass spectrometer 5 according to the present first embodiment calculates the ratio R1 of the ion signal intensities at the time points t1 and t2 respectively when the blank sample is measured using the first mobile phase solvent and the ratio R2 of the ion signal intensities at the time points t1 and t2 respectively when the blank sample is measured using the second mobile phase solvent, compares their difference or ratio with a threshold, and thereby determines whether or not the second mobile phase solvent is contaminated. Thus, since presence and absence of the contamination can be determined without adding an internal standard substance, it can be avoided that the internal standard substance itself acts as a foreign substance.
The mass spectrometer 5 according to the present first embodiment determines contamination of the second mobile phase solvent using the ratio of the ion signal intensities (both of R1 and R2 are calculated as the ratio of the ion signal intensities at the time points t1 and t2 respectively). Instead of the value itself of the ion signal intensity, the ratio of the ion signals of different time points respectively is used, contamination can be thereby determined after suppressing an effect of the machine difference of the device.
When it is determined that the second mobile phase solvent is contaminated, the mass spectrometer 5 according to the present first embodiment notifies the user of the effect and cancels the measurement, or performs measurement after replacing the second mobile phase solvent by another mobile phase solvent. Thus, such event can be avoided that the second mobile phase solvent having been contaminated is used as it is to acquire an erroneous measurement result.
In the first embodiment, explanation was made with an example of measuring the ion signal intensities with respect to specific m/z only. Alternatively, it is also possible to scan a certain range of m/z and to use an ion signal value obtained in the scanning. In the second embodiment of the present disclosure, an example of it will be explained. The configuration of the mass spectrometer 5 is same to that of the first embodiment.
The mass spectrometer 5 measures the ion detection signal with respect to each of the first mobile phase solvent (one expressed as “new” in
In the second embodiment, the mass spectrometer 5 performs the scan mode, and the total ion chromatogram is thereby obtained with respect to a certain range of m/z. The ion signal obtained then is plotted on the vertical axis, m/z is plotted on the horizontal axis, and a mass spectrum is thereby obtained simultaneously. Using this mass spectrum, the composition and the amount of a foreign substance contained within the second mobile phase solvent can be analyzed. Along with the contamination determination result, the mass spectrometer 5 may produce an analysis result of it. However, since the measurement accuracy in the scan mode is lower than that in the SIM mode and the MRM mode, it is considered to be preferable that the composition and the amount of the foreign substance analyzed by the scan mode are to be deemed as a surmised result.
In the SIM mode and the MRM mode of the mass spectrometer 5, an ion signal is obtained with respect to a single m/z only, and therefore there are advantages that the measurement time is short and many data points are obtained (namely the resolution of the measurement result is high). However, the mass spectrum cannot be obtained. On the other hand, in the scan mode, since an ion signal is obtained over a m/z range of a certain degree, there is an advantage that a mass spectrum can be obtained although the measurement time is long. It is also possible to combine these modes and to use the advantages of the both.
For example, in order to determine whether or not the second mobile phase solvent is contaminated, the SIM mode or the MRM mode is performed first to acquire a chromatogram signal intensity, and the flowchart of
Also, the present disclosure is not to be limited to the embodiments described above, and various modifications are to be included. For example, the embodiments described above were explained in detail for easy understanding of the present disclosure, and are not to be necessarily limited to those including all configurations explained. Also, a part of a configuration of an embodiment can be replaced by a configuration of another embodiment, and a configuration of an embodiment can be added with a configuration of another embodiment. Also, with respect to a part of a configuration of each embodiment, it is possible to add, delete, and substitute other configurations. Further, the control line and the information line are shown for those considered to be necessary for explanation, and all control lines and information lines of the product have not necessarily been shown. In fact, it can be considered that almost all configurations are connected to each other.
In the embodiments described above, explanation was made on a premise that the first mobile phase solvent (or a separate fresh mobile phase solvent in replacing the second mobile phase solvent) was not contaminated. Although it is preferable that the first mobile phase solvent is not contaminated since the first mobile phase solvent becomes a reference of presence and absence of contamination, when it can be secured that the degree of contamination is less than a predetermined reference value according to a required determination accuracy and the like for example, such mobile phase solvent may be used as the first mobile phase solvent. In the embodiments described above, each flowchart can be performed by a calculation device such as the data processing unit 560 for example, and may be performed also by that an operator operates manually the mass spectrometer 5.
| Number | Date | Country | Kind |
|---|---|---|---|
| 2021-162591 | Oct 2021 | JP | national |
| Filing Document | Filing Date | Country | Kind |
|---|---|---|---|
| PCT/JP2022/035211 | 9/21/2022 | WO |
