JP2015055485A - Liquid chromatography mass spectrometry - Google Patents

Abstract

PROBLEM TO BE SOLVED: To provide an LCMS capable of preventing mass information from being dropped as much as possible even if a protection mechanism is activated due to a large amount of ions introduced.SOLUTION: An LCMS 1, which uses an MS detector 23 to scan sample components sequentially eluted from an analytical column 14 within a first mass range and measures MS signal intensity of each mass, comprises: a mass spectrum peak comparison section 33 that, after a threshold A is set, extracts an ion having maximum MS signal intensity Smax in each mass scanning within the first mass range and compares the maximum MS signal intensity Smax with the threshold A; and a mass scanning range changing section 34 that, when the maximum MS signal intensity Smax exceeds the threshold A, sets mass of the ion having the maximum MS signal intensity Smax as base peak mass M/Z and sets a second mass range excluding an adjacent range of the base peak mass M/Z from the first mass range as a new mass scanning range. The LCMS 1 uses the MS detector 23 to continuously measure the second mass range even after the maximum MS signal intensity Smax exceeds the threshold A.

Description

  The present invention relates to a liquid chromatograph mass spectrometer suitable for analyzing a sample in which a large amount of components and a small amount of components are mixed.

  There are cases where it is desired to analyze a substance containing a high concentration main component (major component) and a low concentration impurity (trace component) such as a synthetic product. Liquid chromatograph mass spectrometers (hereinafter also referred to as LCMS) are also used for impurity analysis of such synthetic products. In general, when LCMS qualitative analysis is performed when impurities contained in a sample are unknown, the mass spectrum is continued by repeating high-speed mass scanning with a predetermined mass width that is assumed to be contained in the sample in advance. LCMS scan measurements acquired in this way are used.

By the way, an ion detector (hereinafter also referred to as an MS detector) of an LCMS mass spectrometer (MS unit) not only shakes out an output signal but also contaminates the detector when a large amount of ions are introduced during analysis. There is a risk of damage or poor performance.
Therefore, the amount of ions introduced into the MS detector increases, and a threshold A at which the MS signal intensity of the base peak in the mass spectrum (the signal intensity of the ion emitting the strongest signal in each mass spectrum) is set in advance is set. When the threshold is exceeded, as shown in FIG. 9, there is a device that automatically turns off the detector voltage of the MS detector for a certain time after the threshold A is exceeded, and the protection mechanism of the MS detector works. It is used.

On the other hand, in the MS detector in the ion trap type LCMS, an invention for increasing the apparent dynamic range when the signal intensity increases is already known. In other words, ion trap LCMS has an upper limit on the amount of ions that can be trapped. Therefore, the sample component before ionization eluted from the analytical column is detected using a UV detector (visible ultraviolet light detector) provided in the LC section. When it is estimated from the UV signal intensity by the UV detector that the signal intensity exceeding the upper limit of the dynamic range may be exceeded when the eluted sample component is introduced into the MS section and detected by the MS detector. In US Pat. No. 6,057,049, it is described that the ion introduction time into the ion trap is shortened so that the amount of ions introduced is suppressed, and an MS signal that does not saturate is obtained.
According to this document, a chromatogram is created in real time by the UV detector of the LC section, and the chromatogram measurement data by the UV detector and a predetermined “delay time” (predetermined by a UV detector for a specific component). Based on the detected UV signal and the time difference between the MS signal detected by the MS detector for the same component), the start time and end time of each peak at which the sample component is detected by the MS detector are acquired. Furthermore, when the signal intensity of the UV signal at each time point during peak detection is obtained and judged from the signal intensity at the UV detector, there exists a time range X exceeding the intensity corresponding to the upper limit of the dynamic range of the MS detector. A time range X0 that is the same as or slightly larger than the time range X is set, and the ion introduction time into the ion trap is shortened only during the time range X1 that is delayed by a predetermined delay time Δt from the time range X0. Thus, it is disclosed that the signal intensity of the mass spectrometer is not saturated.

JP 2011-002469 A

  In the case of a protection mechanism that prevents ion detection by unconditionally turning off the detector voltage of the MS detector for a certain period after the intensity of the MS signal exceeds the threshold A (see FIG. 9) When the mechanism is activated, detection of all mass spectra within the mass width of the set scanning range is not performed while the MS detector is off. For this reason, the MS signal can be reliably protected from the problem of being saturated continuously for a relatively long period of time, but the elution of the sample component that causes the MS signal to increase in intensity finishes in a short time and immediately falls below the threshold value. However, since the measurement is not resumed for a certain period until the off period of the MS detector ends, as shown by an arrow in FIG. Even if there is, there is a possibility that the information on the component cannot be completely detected, and the presence of such an impurity component may be completely missed.

  In the protection mechanism described in Patent Document 1 described above, whether or not protection is actually required is determined based on the signal strength of the MS detector, but is determined based on the signal strength of the UV detector. For this reason, it is necessary to appropriately adjust the threshold setting and “delay time” setting for determination by the UV detector to the signal intensity that requires protection of the MS detector. In addition, it was difficult to adjust properly. In other words, if the threshold value is too high, the protection function will not operate sufficiently, and if the threshold value is too low, the protection function will operate for a long time, causing inconvenience that it is impossible to detect even a period when protection is unnecessary. .

  Therefore, the present invention provides a new protection mechanism for the MS detector in LCMS, so that even if a large amount of ions are introduced and the protection mechanism is activated, the mass information that can be lost can be reduced as much as possible. An object is to provide a chromatographic mass spectrometer.

The liquid chromatograph mass spectrometer of the present invention, which has been made to solve the above problems, introduces ions generated by ionizing sample components sequentially eluted from the analytical column into the mass analyzer, and sets a predetermined mass width. Is a liquid chromatograph mass spectrometer that measures the MS signal intensity of each mass with an MS detector that repeatedly scans the first mass range of the first mass range and detects the ions, and has the following configuration.
That is, a threshold for the detected MS signal intensity is set in the MS detector, and ions having the maximum MS signal intensity are extracted each time mass scanning of the first mass range is performed. A mass spectrum peak comparison unit that compares the mass of the base peak mass from the first mass range with the mass of the ion having the maximum MS signal intensity as the base peak mass when the maximum MS signal intensity exceeds the threshold. A mass scanning range changing unit that changes the second mass range excluding the neighboring range to a new mass scanning range, and the MS detector is used for the second mass range even after the maximum MS signal intensity exceeds the threshold. We are trying to measure continuously.

According to the present invention, when the measurement is started, the mass spectrum of the entire first mass range is continued by repeating the mass scan of the entire first mass range while the intensity of the MS signal of the MS detector does not exceed the threshold value. Get. Then, for each mass scan in the first mass range, ions having the maximum MS signal intensity are extracted, and the maximum MS signal intensity is compared with a threshold value. When the maximum MS signal intensity exceeds the threshold value, the mass of the ion having the maximum MS signal intensity is set as the base peak mass, and the second mass range obtained by excluding the vicinity range of the base peak mass from the first mass range is newly set. The mass scanning range is set, and thereafter, mass scanning in the second mass range is performed. Therefore, it excludes the vicinity of the mass range of the excessive ions that caused the threshold to be exceeded, and continues for the other mass ranges without turning off the MS detector. It is possible to eliminate loss of mass information outside the included mass range.
Also, rather than judging when the signal of another detector exceeds the threshold set for the other detector, the maximum MS signal strength of the MS detector currently being measured exceeds the threshold for the MS signal. Since the mass scanning range is changed from the point in time, the mass scanning range can be switched in accordance with the signal intensity required to protect the MS detector accurately.

In the above invention, the base peak mass is M / Z (where M is the mass and Z is the charge of the ion), and at least the mass range excluding M / Z to (M / Z) +2 from the first mass range is the second mass. The range is preferable.
By excluding (M / Z) +1, (M / Z) +2, which is the mass when the isotope is present, together with the base peak mass (M / Z) of the ion that gives the maximum MS signal intensity, Most of the ions introduced in a large amount can be excluded, and the influence of excessive ions can be suppressed.

In the above invention, a pre-detector for detecting a sample component before ionization is further provided at a position behind the analytical column and in front of the mass analyzer, and the MS detector is a predetermined detector from the pre-detector. The flow path is configured so that the same sample component is detected with a delay of time difference ΔT, and the pre-detector signal data detected by the pre-detector is detected by the MS detector with a delay of time difference ΔT. MS signal data stored in the data storage unit in association with the MS signal data, and when the maximum MS signal intensity exceeds the threshold value, the MS signal data when the threshold value is exceeded from the pre-detector signal data stored in the data storage unit; An alternative threshold setting unit that extracts the associated pre-detector signal data retroactively and sets it as an alternative threshold corresponding to the threshold, and after the mass scanning range is changed to the second mass range, Signal strength and A pre-detector signal comparison unit for comparing with an alternative threshold, and a mass scanning range of the MS detector when a predetermined time difference ΔT has elapsed since the signal intensity of the pre-detector becomes smaller than the alternative threshold again. May be provided with a mass scanning range restoring unit that returns the second mass range to the first mass range.
According to this, after changing to the second mass range, the signal intensity of the sample component that causes the excessive ions can be confirmed by the pre-detector, so that the signal intensity of the pre-detector is the substitute threshold value. When it becomes smaller than this, it is possible to return to the first mass range, and it is possible to reduce the loss of mass information.

In this case, the second mass range may exclude the entire mass scanning range of the first mass range. That is, once the maximum MS signal strength exceeds the threshold, once the entire mass scan of the first mass range is stopped and the signal strength of the pre-detector becomes smaller again than the alternative threshold, the MS The mass scanning range of the detector may be returned to the first mass range.
Thereby, after the maximum MS signal strength exceeds the threshold value, the MS detector can be reliably protected until the signal strength of the pre-detector becomes smaller than the alternative threshold value again.

The block diagram of the liquid chromatograph mass spectrometer which is one Embodiment of this invention. The flowchart which shows the procedure of the measurement operation by LCMS of FIG. FIG. 3 is a relationship diagram between an MS signal measured in the operation flow of FIG. 2 and a mass scanning range at each time point. The block diagram of the liquid chromatograph mass spectrometer which is other one Embodiment of this invention. The flowchart which shows the procedure of the measurement operation by LCMS of FIG. FIG. 6 is a relationship diagram between the signal intensity P at each time point of the UV detector and the signal intensity at each time point of the MS detector and the mass scanning range when measured in the operation flow of FIG. 5. FIG. 6 is a diagram illustrating the relationship between the signal intensity P at each time point of the UV detector and the signal intensity at each time point of the MS detector and the mass scanning range when the operation flow of FIG. 5 is partially deformed and measured. The block diagram of the liquid chromatograph mass spectrometer which is another one Embodiment of this invention. The figure explaining an example of the protection mechanism of the conventional MS detector.

(Embodiment 1)
Hereinafter, embodiments of the present invention will be described with reference to the drawings.
FIG. 1 is a diagram showing a configuration of a liquid chromatograph mass spectrometer (LCMS1) according to an embodiment of the present invention.
The LCMS 1 is roughly divided into an LC unit 10 and an MS unit 20. The LC unit 10 includes a liquid feed pump 12 that sends out a solvent supplied from a solvent container 11 (reservoir) as a carrier liquid, a sample introduction unit 13 that introduces a sample, and an analysis column 14 that separates sample components in the carrier liquid for each component. Consists of. A detector 15 such as a UV detector or a PDA (photodiode array) detector may be provided after the analytical column 14 in order to detect the eluted components of the analytical column 14 and create a chromatogram. In form 1, it is not always necessary.

  The MS unit 20 is an ionization unit 21 that ionizes sample components eluted from the analysis column 14 by ESI method, APCI method, etc., and mass separation that performs mass scanning for mass separation of the generated ions and passing specific ions And an ion detector 23 for detecting ions that have passed through the mass separator 22. In the following description, the ion detector 23 that detects ions after mass separation by mass scanning by the mass separator 22 is referred to as an MS detector 23, and is attached to the LC unit 10 side in an embodiment to be described later. This is distinguished from the UV detector (pre-detector) that detects the sample components.

  The LCMS 1 includes a control unit 30 including hardware such as a CPU and an HDD and software in order to control the measurement operation. The control unit 30 operates the liquid feed pump 12 of the LC unit 10 to send the sample injected from the sample introduction unit 13 to the analysis column 14 and perform component separation control. In addition, the sample components that are sequentially eluted from the analytical column 14 are ionized by the ionization unit 21, the generated ions are introduced into the mass separator 22, and mass scanning is performed to separate the ions by mass. Then, control is performed to detect the amount of ions for each mass separated by the MS detector 23 as the MS signal S.

  The mass separator 22 presets the mass width for which mass scanning is desired. This set mass range is referred to as a first mass range. For example, in the analysis of a synthetic product including a main component and an impurity component, the first mass range is set so as to include the mass of ions attributed to the main component and the mass of ions attributed to the impurity. The control unit 30 repeatedly scans the mass of the first mass range at high speed, detects the MS signal S of each mass in the first mass range for the sample components sequentially eluted from the analysis column 14, and detects the mass spectrum. Obtain continuously so that it can be created in time series.

  The MS signal S of each mass acquired by the MS detector 23 is accumulated as MS signal data S in the data storage unit 31. By calculating the accumulated MS signal data S, it can be extracted as a mass spectrum at a specific point in time, extracted as a mass chromatogram for a specific mass, or extracted as a total ion chromatogram. It becomes like this.

Moreover, the control part 30 is provided with the threshold value memory | storage part 32, the mass spectrum peak comparison part 33, and the mass scanning range change part 34 as a characteristic structure.
The threshold storage unit 32 stores a threshold A as a determination value for operating the protection mechanism when excessive ions are introduced into the MS detector 23 and the signal intensity of the MS detector rises.

  Each time mass scanning of the first mass range is performed, the mass spectrum peak comparison unit 33 extracts ions having the maximum MS signal intensity, and performs an operation of comparing the maximum MS signal intensity Smax with the threshold A.

  When the maximum MS signal intensity Smax exceeds the threshold value A, the mass scanning range changing unit 34 sets the mass of the ion having the maximum MS signal intensity as the base peak mass (the mass corresponding to the ion with the highest signal intensity) M. / Z (M is the mass, Z is the charge of the ion), and control to change the second mass range excluding the range near the base peak mass M / Z from the first mass range to a new mass scanning range Do.

  In other words, a second mass range is set that excludes a predetermined mass width in the vicinity of the base peak mass M / Z that is the cause of excessive ions, the mass scanning range is switched from the first mass range to the second mass range, and MS detection is performed. Continue the measurement without turning off the instrument. Specifically, as the predetermined mass width, at least the base peak mass (M / Z) and the mass ranges of isotopes (M / Z) +1 and (M / Z) +2 are excluded. To do. In the present embodiment, as the predetermined mass width, from (M / Z) -1 which is smaller by the mass number 1 than the base peak mass M / Z, by a mass number 1 which is larger than the isotope mass (M / Z) +2 (M / Z) +3 (the range of the mass number width is 5) is excluded to obtain a new mass scanning range. Thus, the second mass range excluding the vicinity range “(M / Z) −1 to (M / Z) +3” of the base peak mass is set from the first mass range, and the base peak mass (M / Z) After the intensity of the MS signal S exceeds the threshold A, scanning in the second mass range can prevent the signal from being broken due to excessive ions, so the MS detector should be turned off. Measurement can continue.

  Since the charge of the ion may be other than 1, for convenience of explanation, as described above, the charge of the ion is Z, (M / Z) is the base peak mass, and the second mass range is (M / Z) -1, (M / Z), (M / Z) +1, (M / Z) +2, and (M / Z) +3.

Next, the operation of the LCMS 1 of Embodiment 1 will be described.
FIG. 2 is a flowchart showing the procedure of the measurement operation by the LCMS 1 of FIG. FIG. 3 is a diagram showing the relationship between the MS signal S (base peak mass MS signal) and the mass scanning range at each time point as measured in this operation flow.

  Before starting the measurement, a threshold A for setting the protection function when the MS signal intensity of the MS detector 23 starts to rise rapidly is set in advance, and further, the first mass range M / Z for performing mass scanning is set. The mass width is set (S101). Here, M / Z = 100 to 1000 is set as the first mass range.

  Subsequently, the measurement is started, and the sample components sequentially eluted from the analysis column 14 of the LC unit 10 are repeatedly scanned at high speed in the first mass range, thereby continuing the MS signal S (which becomes a mass spectrum) in the first mass range. And is stored as MS signal data S in the data storage unit 31. In addition, the maximum MS signal intensity Smax is obtained every time the first mass range is scanned (S102).

  The maximum MS signal intensity Smax and the threshold A are compared for each scan of the first mass range (S103). When Smax is smaller than A, the process returns to S102, and when Smax is larger than A, the process proceeds to S104. Here, since Smax has not reached A until time Ta in FIG. 3, S102 is repeated. Then, Smax reaches A at the time Ta when the MS signal S starts to rise.

When the maximum MS signal intensity Smax exceeds the threshold value A, the base peak mass M / Z of the ion showing Smax is extracted, and the vicinity range (M / Z) -1 to (M / Z) +3 of the base peak mass is excluded. The second mass range is set, and the subsequent mass scanning range is switched to the second mass range (S104).
For example, as shown in FIG. 3, if the base peak mass M / Z is 550, the second mass range is set to M / Z = 100 to 548 and M / Z = 554 to 1000.

Subsequently, after time Ta, high-speed scanning measurement is repeated for the second mass range, and the MS signal data S in the second mass range is continuously measured and stored in the data storage unit 31 (S105). After time Ta, the strong MS signal existing at M / Z = 549 to 554 is excluded, so in other mass ranges of M / Z = 100 to 548 and M / Z = 554 to 1000 The base peak mass will be detected.
Thereafter, the measurement in the second mass range is continued until an instruction to end the measurement is given manually or automatically.

  After reaching S105, the process returns to S101 again. If the second mass range in the immediately preceding S105 is replaced with the first mass range in the new S101, and S101 to S105 are repeated, the excess ion Similar processing can be performed even when there are a plurality of types of sample components that cause the above.

  By performing mass analysis according to the above procedure, mass analysis is continued except for the range near the base peak mass, so even if excessive ions of the base peak mass are introduced, the impurity component As long as the mass is not near the base mass, it can be detected reliably.

(Embodiment 2)
Next, Embodiment 2 will be described. In the first embodiment, when the maximum MS signal intensity Smax exceeds the threshold A and shifts to the second mass range, the mass scanning range is not restored to the first mass range thereafter. In the second embodiment, after the mass scanning range is changed to the second mass range, the fact that the maximum MS signal intensity Smax has decreased to the intensity corresponding to the threshold value A is again detected by a detector other than the MS detector (pre-detection). The mass scanning range is restored to the first mass range.

  FIG. 4 is a diagram showing a configuration of LCMS 2 which is another embodiment of the present invention. About the same component as LCMS1 demonstrated in FIG. 1, the description is abbreviate | omitted by attaching | subjecting a same sign. In LCMS2, in order to have a function of restoring the mass scanning range from the second mass range to the first mass range, a UV detector as a pre-detector for detecting sample components before ionization is provided at the rear stage of the analytical column 14. A detector (or PDA detector) 15 is provided.

  The control unit 30a for controlling the LCMS 2 includes a data storage unit 31a, a threshold storage unit 32, a mass spectrum peak comparison unit 33, a mass scanning range change unit 34, an alternative threshold storage unit 35, and a front detector signal comparison. A unit 36 and a mass scanning range restoring unit 37.

  Among these, the data storage unit 31a accumulates the UV signal data P acquired from the UV detector 15 together with the MS signal data S acquired from the MS detector. Since the same sample component is detected in the accumulated MS signal data S and UV signal data P with a time difference ΔT (“delay time”), the MS signal whose time has elapsed by ΔT with respect to the UV signal data P Data S is associated and stored.

  The mass spectrum peak comparing unit 33 and the mass scanning range changing unit 34 are the same as those in the first embodiment. That is, the mass spectrum peak comparison unit 33 compares the maximum MS signal intensity Smax with the threshold value A stored in the threshold value storage unit 32, and from the point in time when Smax reaches A, the mass scanning range change unit 34 performs the second comparison. Control is performed to change the mass range to a new mass scanning range.

When the maximum MS signal intensity Smax reaches the threshold A, the alternative threshold storage unit 35 stores the UV signal data Pa associated with the MS signal data S at that time in the UV signal accumulated in the data storage unit 31a. Extract from data P. That is, the UV signal data Pa at the time point that is back by “delay time” ΔT is extracted. Then, the signal intensity of the UV signal data Pa is stored as an alternative threshold B corresponding to the threshold A.
After storing the substitute threshold B, the measurement of the UV signal P from the UV detector 15 is continued. Assuming that the UV signal P again becomes the alternative threshold B at a certain point in time, it can be estimated that the MS signal S has reached the threshold A (that is, the value is Smax) when the “delay time” ΔT has elapsed since then. become.

The pre-detector signal comparison unit 36 performs an operation of comparing the UV signal data P of the UV detector 15 with the alternative threshold B after the mass scanning range is changed to the second mass range.
When the intensity of the UV signal data P of the UV detector 15 becomes smaller than the alternative threshold B again, the mass scanning range restoring unit 37 detects the mass scanning range of the MS detector 23 when the time difference ΔT elapses from that point. Is controlled from the second mass range to the first mass range.

Next, the operation of the LCMS 2 will be described.
FIG. 5 is a flowchart showing the procedure of the measurement operation by the LCMS 2 of FIG. FIG. 6 is a diagram for explaining the relationship between the signal intensity P at each time point of the UV detector and the signal intensity at each time point of the MS detector and the mass scanning range when measured by this flow. .

Before starting the measurement, the threshold A for setting the protection function when the signal intensity starts to rise rapidly in the MS detector 23 is set in advance, and the mass in the first mass range M / Z for performing mass scanning is further set. A width is set (S201). In this case, M / Z = 100 to 1000 is set as the first mass range.
Furthermore, a time difference ΔT that is a delay time is set. For example, in a preliminary experiment before the start of measurement, the time difference ΔT is injected with a standard sample from the sample introduction unit 13, and a signal peak expressed by the sample is detected by the UV detector 15 and the MS detector 23. By measuring, it can be stored as the delay time ΔT.

  Subsequently, measurement is started, and the sample components sequentially eluted from the analysis column 14 of the LC unit 10 are measured by the UV detector 15 and accumulated as UV signal data P. Further, the MS signal 23 is repeatedly measured in the first mass range by the MS detector 23, whereby the MS signal S in the first mass range is continuously measured and stored as the MS signal data S in the data storage unit 31. At this time, the UV signal data P stored earlier by the delay time ΔT and the current MS signal data S are stored in association with each other. Further, every time the first mass range is scanned, the maximum MS signal intensity Smax is extracted (S202).

  The maximum MS signal intensity Smax is compared with the threshold A for each scan of the first mass range (S203). When Smax is smaller than A, the process returns to S202, and when Smax is larger than A, the process proceeds to S204. Here, since the threshold value A has not been reached until time Ta in FIG. 6, the operation of S202 is repeated. The MS signal data S starts to rise and reaches the threshold A at time Ta.

When the maximum MS signal intensity Smax exceeds the threshold value A, the base peak mass M / Z of the ion showing Smax is extracted, and the vicinity range (M / Z) -1 to (M / Z) +3 of the base peak mass is excluded. The second mass range is set, and the subsequent mass scanning range is switched to the second mass range (S204).
For example, as shown in FIG. 6, if the base peak mass M / Z is 550, the second mass range is set to M / Z = 100 to 548 and M / Z = 554 to 1000.
At the same time, the UV signal data Pa (Pa in FIG. 6) at the time (Ta−ΔT) that is earlier than the time Ta by the delay time difference ΔT is read from the data storage unit 31a, and this signal intensity is stored as the alternative threshold B.

  Subsequently, after time Ta, scanning measurement is repeated at high speed for the second mass range, and the MS signal S of the second mass range is continuously measured and accumulated in the data storage unit 31a (S205). Also at this time, similarly to the case of the first mass range before changing the mass scanning range, it is accumulated in association with the UV signal data P accumulated earlier by the delay time ΔT.

After the time Ta when the substitute threshold B is set, the UV signal data P from the UV detector 15 is compared with the substitute threshold B, and a time point at which the UV signal data P becomes the substitute threshold B is searched (S206).
The signal intensity of the UV signal data P once increases after the time Ta, but when it exceeds the peak, the signal intensity thereafter decreases and eventually decreases to the substitute threshold B. At the time when the alternative threshold B is reached (Pb in FIG. 6), the scanning range of the MS detector 23 is restored from the second mass range to the first mass range at time Tb when the time difference Δt has passed since that time (S207). ). That is, the mass scanning range is returned to M / Z = 100 to 1000.

  With the above operation flow, the mass scanning range can be changed from the first mass range to the second mass range excluding the vicinity of the base peak mass for the truly required period, so that the mass information is not missed. Can do.

(Embodiment 3)
In Embodiment 2 described above, as the second mass range, only the range near the base peak mass that causes excessive ions exceeding the threshold A is excluded, so that the mass information is not missed as much as possible. .
On the other hand, in the third embodiment, the procedure of the processing flow is almost the same as in the second embodiment, but the range excluded from the set second mass range is the entire first mass range, and the scanning range is the first. When the mass range is changed from one mass range to the second mass range, all mass scans are stopped, the UV signal data P drops to the alternative threshold B, and the mass scan range is restored to the first mass range again. To resume.
In this case, as seen in FIG. 7, the MS signal cannot be completely acquired between the times Ta and Tb, but the MS detector can be reliably protected. And since it is made to return to the time when excessive ions disappear, the period during which mass information is missed can be made the minimum source.

  Further, as shown in FIG. 8, a switching valve 16 for switching the flow path to the drain side is provided after the UV detector 15 in the LCMS 2 shown in FIG. , During the period up to time Tb-ΔT (that is, when the alternative threshold value B is reached again), a control for sending the eluted sample to the drain and returning the flow path to the MS detector side again at time Tb-ΔT is added. You may do it. As a result, the amount of sample components causing excessive ions to be sent to the MS unit 20 side can be reduced as much as possible, so the effect of preventing contamination of the MS unit 20 can be expected.

  The present invention can be applied to an LCMS apparatus.

LCMS1, LCMS2 Liquid chromatograph mass spectrometer 10 LC section 14 Analysis column 15 UV detector (pre-detector)
20 MS part 21 Ionization part 22 Mass separation part 23 Mass detector (MS detector)
30, 30a Control unit 31, 31a Data storage unit 32 Threshold storage unit 33 Mass spectrum peak comparison unit 34 Mass scanning range change unit 35 Alternative threshold storage unit 36 Pre-detector signal comparison unit 37 Mass scanning range restoration unit

Claims (4)

An MS detector that ionizes sample components that are sequentially eluted from the analytical column and introduces the generated ions into the mass spectrometer and repeatedly scans the first mass range with a preset mass width to detect the ions. A liquid chromatograph mass spectrometer that measures the MS signal intensity of each mass,
The MS detector has a threshold for the detected MS signal strength,
A mass spectrum peak comparison unit that extracts ions having the maximum MS signal intensity each time a mass scan of the first mass range is performed, and compares the maximum MS signal intensity with the threshold value;
When the maximum MS signal intensity exceeds the threshold, the second mass range obtained by excluding the vicinity range of the base peak mass from the first mass range is defined as the mass of the ion having the maximum MS signal intensity as the base peak mass. A mass scanning range changing unit for changing to a new mass scanning range,
Even after the maximum MS signal intensity exceeds the threshold, the second mass range is continuously measured by an MS detector.   Assuming that the base peak mass is M / Z (where M is the mass and Z is the charge of the ions), the mass range excluding (M / Z) to (M / Z) +2 from the first mass range is the second mass range. The liquid chromatograph mass spectrometer according to claim 1. A pre-detector for detecting a sample component before ionization is further provided at a position behind the analytical column and in front of the mass analyzer, and the MS detector is provided with a predetermined amount from the pre-detector. The flow path is configured so that the same sample component is detected with a delay of time difference ΔT,
The pre-detector signal data detected by the pre-detector is accumulated in the data storage unit in association with the MS signal data detected by the MS detector with a delay of the time difference ΔT.
When the maximum MS signal intensity exceeds the threshold, the pre-detector signal data associated with the MS signal data when the pre-detector signal data stored in the data storage unit exceeds the threshold. An alternative threshold storage unit that retrospectively extracts and stores as an alternative threshold corresponding to the threshold;
After the mass scanning range is changed to the second mass range, a pre-detector signal comparison unit that compares the signal strength of the pre-detector with the alternative threshold value;
When a predetermined time difference ΔT has elapsed from when the signal intensity of the front detector becomes smaller than the alternative threshold again, the mass scanning range of the MS detector is returned from the second mass range to the first mass range. The liquid chromatograph mass spectrometer according to claim 1, further comprising a mass scanning range restoring unit.   4. The liquid chromatograph mass spectrometer according to claim 3, wherein the second mass range excludes the entire mass scanning range of the first mass range.

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