Mass analysis method and mass analysis device

Abstract

This mass analysis method uses a mass analysis device (100) capable of performing MS analysis and MS / MS analysis under each of a first state for detecting a first ion and a second state for detecting a second ion having a polarity opposite to that of the first ion. The mass analysis method comprises: a step (S12) for performing a first ion selection process of selecting a first ion for analysis by a first MS / MS analysis executed under the first state on the basis of a result of a first MS analysis executed under the first state; and a first selection process (S22) of selecting a second ion for analysis by a second MS / MS analysis executed under the second state on the basis of a result of a second MS analysis executed under the second state and a first feature quantity corresponding to the first ion selected in the first ion selection process.

Description

Mass spectrometry method and mass spectrometry device

[0001] The present disclosure relates to a mass spectrometry method using a mass spectrometer capable of performing MS (mass spectrometry) analysis and MS / MS analysis, and to the mass spectrometer.

[0002] There is known a mass spectrometer that can perform both MS analysis, which performs mass analysis on a group of ions obtained by ionizing a sample, and MS / MS analysis, which performs mass analysis on a group of ions obtained by fragmenting selected ions from the group of ions obtained by ionizing a sample. In MS / MS analysis, the ions before fragmentation are called "precursor ions," and the ions obtained by fragmenting the precursor ions are called "product ions."

[0003] Known mass spectrometry methods include targeted analysis, in which precursor ions to be analyzed in MS / MS analysis are determined in advance, and non-targeted analysis, in which precursor ions are determined based on peak intensities in the MS spectrum obtained by MS analysis.

[0004] Known examples of non-target analysis include a technique called data dependent acquisition (DDA), in which ions corresponding to peaks with high peak intensities among all peaks in an MS spectrum are targeted for MS / MS analysis.

[0005] Furthermore, some compounds in a sample tend to become positive ions, while others tend to become negative ions. Therefore, when it is desired to obtain a large amount of information about the compounds in a sample, mass spectrometry may be performed while switching polarity to perform positive ion measurements to detect positive ions and negative ion measurements to detect negative ions.

[0006] Non-Patent Document 1 discloses a mass spectrometry method in which the polarity is switched and MS analysis and MS / MS analysis are performed at each polarity.

[0007] Henrik Carlsson et al., Journal of Chromatography B, 1195 (2022) 123200, https: / / doi.org / 10.1016 / j.jchromb.2022.123200

[0008] When MS analysis and MS / MS analysis are performed at each polarity while switching polarity, if DDA is performed for both positive ion measurement and negative ion measurement, the analytes for the MS / MS analysis in the positive ion measurement and the analytes for the MS / MS analysis in the negative ion measurement are selected based on the results of each individual MS analysis. In other words, even though positive ion measurement and negative ion measurement are performed, the measurement results at each polarity are not referenced to each other, which can result in inefficient analysis.

[0009] An object of the present disclosure is to provide a mass spectrometry method and mass spectrometry apparatus that can efficiently perform MS analysis and MS / MS analysis at each polarity.

[0010] The mass spectrometry method disclosed herein uses a mass spectrometer capable of performing MS analysis, which performs mass analysis on a group of ions obtained by ionizing a sample, and MS / MS analysis, which performs mass analysis on a group of ions obtained by fragmenting selected ions from the group of ions obtained by ionizing the sample. The mass spectrometer can perform MS analysis and MS / MS analysis under each of a first state in which first ions having a first polarity are detected and a second state in which second ions having a second polarity opposite to the first polarity are detected. The mass spectrometry method includes the steps of: performing a first MS analysis under a first state; performing a first ion selection process to select first ions to be analyzed based on the results of the first MS analysis; performing a first MS / MS analysis under the first state using the first ions selected in the first ion selection process as the analysis targets; switching from the first state to a second state; performing a second MS analysis under the second state; performing a second ion selection process to select second ions to be analyzed based on the results of the second MS analysis; and performing a second MS / MS analysis under the second state using the second ions selected in the second ion selection process as the analysis targets. The step of performing the second ion selection process includes a first selection process to select second ions to be analyzed based on the results of the second MS analysis and a first feature corresponding to the selected first ions. The step of performing the second MS / MS analysis includes a second MS / MS analysis using the second ions selected in the first selection process as the analysis targets.

[0011] A mass spectrometer according to the present disclosure is capable of performing MS analysis, which performs mass analysis on a group of ions obtained by ionizing a sample, and MS / MS analysis, which performs mass analysis on a group of ions obtained by fragmenting selected ions from the group of ions obtained by ionizing the sample. The mass spectrometer includes a measurement unit having a mass separation unit that separates ions according to their mass-to-charge ratio, a power supply unit that applies a voltage to the mass separation unit, and a controller that controls the measurement unit and the power supply unit. The mass spectrometer is capable of performing MS analysis and MS / MS analysis under two states: a first state in which first ions having a first polarity are detected, and a second state in which second ions having a second polarity opposite to the first polarity are detected. The controller controls the measurement unit and power supply unit to perform a first MS analysis under a first state, performs a first ion selection process to select first ions to be analyzed based on the results of the first MS analysis, controls the measurement unit and power supply unit to perform a first MS / MS analysis under the first state using the first ions selected in the first ion selection process as the analysis target, controls the power supply unit to switch from the first state to the second state to apply a voltage to the mass separation unit, controls the measurement unit and power supply unit to perform a second MS analysis under the second state, performs a second ion selection process to select second ions to be analyzed based on the results of the second MS analysis, and controls the measurement unit and power supply unit to perform a second MS / MS analysis under the second state using the second ions selected in the second ion selection process as the analysis target. The step of performing the second ion selection process includes a step of performing a first selection process to select second ions to be analyzed based on the results of the second MS analysis and a first feature amount corresponding to the selected first ions. The step of performing the second MS / MS analysis includes a step of performing the second MS / MS analysis on the second ions selected in the first selection process as the analysis target.

[0012] According to the present disclosure, the second ions to be analyzed in the second MS / MS analysis are selected based on the results of the second MS analysis and the feature quantities corresponding to the first ions to be analyzed in the first MS / MS analysis, thereby enabling the selection of the analytes with higher selectivity, thereby enabling more efficient mass analysis of the sample.

[0013] FIG. 1 is a schematic diagram of a mass spectrometer according to a first embodiment; FIG. 2 is a schematic diagram showing the flow of a mass analysis method according to a first embodiment; FIG. 3 is a flowchart of a first negative ion selection process; FIG. 4 is a flowchart of a second positive ion selection process; FIG. 5 is a flowchart of a first feature amount calculation process; FIG. 6 is a diagram showing an example of a first feature amount group associated with one analysis target; FIG. 7 is a schematic diagram showing the flow of a mass analysis method according to a second embodiment; FIG. 8 is a schematic diagram showing the flow of a mass analysis method according to a third embodiment; FIG. 9 is a schematic diagram showing the flow of a mass analysis method according to a fourth embodiment; and FIG. 10 is a schematic diagram showing the flow of a mass analysis method according to a fifth embodiment.

[0014] Hereinafter, embodiments of the present disclosure will be described in detail with reference to the drawings. In the drawings, the same or corresponding parts are designated by the same reference numerals, and description thereof will not be repeated.

[0015] First Embodiment [Mass Spectrometer] FIG. 1 is a schematic diagram of a mass spectrometer according to a first embodiment. The mass spectrometer 100 is a quadrupole time-of-flight (Q-TOF) mass spectrometer. While the mass spectrometer 100 will be described below as a Q-TOF mass spectrometer, any mass spectrometer can be used as long as it is capable of performing both MS analysis, which performs mass analysis on ions obtained by ionizing a sample, and MS / MS analysis, which performs mass analysis on ions obtained by fragmenting selected ions from the ions obtained by ionizing the sample. For example, the mass spectrometer 100 may be a tandem mass spectrometer, such as a tandem quadrupole (QQ) or tandem flight (TOF-TOF) mass spectrometer. It may also be a hybrid mass spectrometer, such as a Q-TOF, ion trap time-of-flight (IT-TOF), quadrupole ion cyclotron resonance (Q-ICR), or Q-Fourier transform. In the following, MS analysis may be referred to as "MS1 analysis," and MS / MS analysis may be referred to as "MS2 analysis." In addition, in MS / MS analysis, ions before fragmentation may be referred to as "precursor ions," and ions obtained by fragmenting the precursor ions may be referred to as "product ions."

[0016] The mass spectrometer 100 includes a measurement device 2 that ionizes a sample, separates the ions according to their mass-to-charge ratio, and measures each ion, a power supply device 4 that applies voltage to each electrode provided in the measurement device 2, and a data processing device 6 that controls the measurement device 2 and the power supply device 4.

[0017] The measuring device 2 includes an ionization chamber 200, which is in a substantially atmospheric pressure atmosphere, and a vacuum chamber 20, the interior of which is divided into four sections. The vacuum chamber 20 is divided into a first intermediate chamber 201, a second intermediate chamber 202, a first analysis chamber 203, and a second analysis chamber 204, and each chamber is evacuated by a vacuum pump (not shown) so that the degree of vacuum increases in that order.

[0018] The ionization chamber 200 is provided with an electrospray ionization (ESI) source 21 that ionizes compounds in the sample liquid by spraying the sample liquid while imparting an electric charge to the sample liquid. The method for ionizing compounds is not limited to this, and other ion sources, such as an atmospheric pressure chemical ionization source, may also be used. Furthermore, an ion source that ionizes gaseous or solid samples, rather than liquid samples, may also be used.

[0019] For example, a liquid chromatograph is connected to the mass spectrometer 100, and the eluate from the liquid chromatograph is continuously introduced into the ion source. Alternatively, a liquid sample may be continuously introduced into the ion source by flow injection analysis. Alternatively, a sample may be intermittently introduced into the mass spectrometer 100.

[0020] The ionization chamber 200 and the first intermediate chamber 201 are connected by a desolvation tube 22. Ions derived from sample components and fine charged droplets generated in the ionization chamber 200 are drawn into the desolvation tube 22 and sent to the first intermediate chamber 201 mainly due to the pressure difference between the ionization chamber 200 and the first intermediate chamber 201. The desolvation tube 22 is, for example, a heated capillary, and when the charged droplets pass through the inside of the desolvation tube 22, evaporation of the solvent in the droplets progresses, promoting the generation of ions.

[0021] A multipole ion guide 23 is disposed in the first intermediate chamber 201. The ions sent to the first intermediate chamber 201 are focused by the ion guide 23 to the vicinity of the ion optical axis C1, and are sent to the second intermediate chamber 202 through an opening at the top of the skimmer 24.

[0022] A multipole ion guide 25 is disposed in the second intermediate chamber 202. The ions sent to the second intermediate chamber 202 are sent from the second intermediate chamber 202 to the first analysis chamber 203 by the ion guide 25.

[0023] The first analysis chamber 203 contains a quadrupole mass filter 26 that separates ions according to their mass-to-charge ratio (m / z), a collision cell 27 for generating product ions, and a part of a transfer electrode 29 that transports ions ejected from the collision cell 27.

[0024] An ion guide 28 is disposed in the collision cell 27. A collision gas such as argon or nitrogen is supplied continuously or intermittently into the collision cell 27.

[0025] As described above, the mass spectrometer 100 is capable of performing both MS1 and MS2 analyses. When performing MS1 analysis, i.e., when measuring ions without fragmenting them, only a radio-frequency voltage for transporting ions is typically applied to the quadrupole mass filter 26. Furthermore, a radio-frequency voltage for transporting ions to the ion guide 28 is applied without supplying collision gas to the collision cell 27. As a result, the ions entering the first analysis chamber 203 pass directly through the quadrupole mass filter 26 and the collision cell 27 and are sent to the transfer electrode 29.

[0026] On the other hand, when MS2 analysis is performed, i.e., when precursor ions are selected and product ions generated by fragmenting the selected precursor ions are measured, a predetermined voltage consisting of a DC voltage superimposed with an RF voltage is applied to the quadrupole mass filter 26. As a result, of the ions entering the first analysis chamber 203, ions having a mass-to-charge ratio corresponding to the voltage applied to the quadrupole mass filter 26 are selected as precursor ions, pass through the quadrupole mass filter 26, and are sent into the collision cell 27. A collision gas is supplied continuously or intermittently into the collision cell 27. The precursor ions sent into the collision cell 27 come into contact with the collision gas and are dissociated by collision-induced dissociation, becoming various product ions, which are sent to the transfer electrode 29.

[0027] The ions emitted from the collision cell 27 are converged by a transfer electrode 29 to form a highly parallel ion flow, which is then sent to a second analysis chamber 204. The second analysis chamber 204 is equipped with an orthogonal acceleration electrode 30, an acceleration electrode 31, a flight tube 32, a reflectron 33, a back plate 34, a detector 35, and the like. The ions, which have become a highly parallel ion flow and have been sent to the second analysis chamber 204, are emitted by the orthogonal acceleration electrode 30 in a direction substantially perpendicular to the direction of incidence of the ion flow.

[0028] The ions are ejected from the orthogonal acceleration electrode 30 in pulses, i.e., as a single ion packet. The ions ejected from the orthogonal acceleration electrode 30 are further accelerated by the acceleration electrode 31 and introduced into the flight space within the flight tube 32. The flight tube 32, reflectron 33, and back plate 34 form an electric field within the flight space that causes the ions to turn back along a path as indicated by C2 in FIG. 1 . As a result, the ions turn back and fly again within the flight tube 32 before reaching the detector 35. The detector 35 outputs an ion intensity signal corresponding to the amount of incident ions and the time at which the ions reach the detector 35 to the data processing device 6.

[0029] The ions sent to the second analysis chamber 204 are given a certain amount of kinetic energy by the orthogonal acceleration electrode 30 and introduced into the flight space. Because ions with smaller mass-to-charge ratios are accelerated faster by the orthogonal acceleration electrode 30, the arrival time at the detector 35 varies depending on the mass-to-charge ratio of the ions, and the ions are separated according to their mass-to-charge ratio. In other words, the mass separation unit that separates ions according to their mass-to-charge ratio includes at least the orthogonal acceleration electrode 30, acceleration electrode 31, flight tube 32, and back plate 34, which are arranged in the second analysis chamber 204.

[0030] The power supply 4 applies predetermined voltages to the orthogonal acceleration electrode 30, the acceleration electrode 31, the flight tube 32, and the back plate 34. Although not shown, the power supply 4 also applies predetermined voltages to the ion optical system, such as the ion guides 23, 25, and 28, the transfer electrode 29, and the quadrupole mass filter 26.

[0031] The power supply unit 4 applies a negative or positive voltage to each electrode, including the orthogonal acceleration electrode 30, the acceleration electrode 31, the flight tube 32, and the back plate 34, in accordance with instructions from the data processing unit 6. For example, when performing mass analysis on positive ions among the ions ejected from the collision cell 27, the power supply unit 4 applies a negative voltage to each electrode. On the other hand, when performing mass analysis on negative ions among the ions ejected from the collision cell 27, the power supply unit 4 applies a positive voltage to each electrode.

[0032] In the following, the state in which a negative voltage is applied to each electrode to perform mass analysis on positive ions may be referred to as the “first state,” and the state in which a positive voltage is applied to each electrode to perform mass analysis on negative ions may be referred to as the “second state.” In other words, the power supply device 4 switches the state of the mass spectrometer 100 between the first state and the second state in accordance with instructions from the data processing device 6.

[0033] The data processing device 6 functions as a control device that controls the measuring device 2 and the power supply device 4, and as a processing device that processes measurement results such as ion intensity signals sent from the detector 35. Note that the mass spectrometer 100 may have separate devices that have the function of controlling the measuring device 2 and the power supply device 4 and the function of processing measurement results.

[0034] For example, the data processing device 6 converts the arrival time of the ions, which corresponds to the flight time of the ions sent from the data processing device 6, into a mass-to-charge ratio based on pre-prepared information, and creates a mass spectrum showing the relationship between the mass-to-charge ratio and the ion intensity.

[0035] The data processing device 6 is typically a computer and includes a control unit 60, a display 64, and an input device 65. The control unit 60 has a processor 61, a memory 62, and an input / output I / F 63. The components within the control unit 60 are communicably connected to one another via a bus.

[0036] The processor 61 is typically an arithmetic processing unit such as a CPU (Central Processing Unit) or an MPU (Micro Processing Unit). The processor 61 controls the operation of the data processing device 6 by reading and executing programs stored in the memory 62. The programs include a program that, when executed by a computer, causes the computer to control the measuring device 2 and the power supply device 4.

[0037] The memory 62 is realized by a storage device such as a read-only memory (ROM), a random access memory (RAM), or a hard disk drive (HDD). The ROM can store programs executed by the processor 61. The RAM can temporarily store data used during execution of the programs by the processor 61 and can function as a temporary data memory used as a work area. The HDD is a non-volatile storage device. A semiconductor storage device such as a flash memory may be used in addition to or instead of the HDD. The programs and / or data may be stored in an external storage device accessible by the processor 61.

[0038] The input / output I / F 63 is an interface for exchanging various types of data between the processor 61 and external devices connected to the input / output I / F 63. The external devices include a display 64, an input device 65, a detector 35, and a power supply 4. The display 64 displays, for example, an image for receiving input from the input device 65 and processing results of the processor 61, such as analysis results. The input device 65 is typically composed of a touch panel, a keyboard, a mouse, etc. The input device 65 receives input operations from the user to the processor 61.

[0039] As described above, the mass spectrometer 100 is capable of performing MS analysis and MS / MS analysis, and can measure both positive and negative ions by switching the polarity of the voltage applied by the power supply 4. The power supply 4 is configured to rapidly switch the voltage polarity, and the data processing device 6 corrects deviations in the mass-to-charge ratio caused by fluctuations in the voltage after switching. Therefore, in the mass spectrometer 100, the waiting time for measurement associated with switching measurement modes is one second or less. Methods for rapidly switching the voltage polarity and specific correction methods can be adopted that are well known to those skilled in the art.

[0040] In this way, the mass spectrometer 100 can switch polarities quickly with a short measurement wait time associated with switching polarities, and can therefore perform mass analysis in both the first and second states on a sample introduced into the measuring device 2 at a given time.

[0041] [Overview of Mass Analysis Method] The data processing device 6 controls the measuring device 2 and the power supply device 4 so that an MS1 ​​analysis under a first state, an MS2 analysis under the first state, an MS1 ​​analysis under a second state, and an MS2 analysis under the second state are performed in this order. Note that the data processing device 6 may also control the measuring device 2 and the power supply device 4 so that another analysis is performed between each analysis. The data processing device 6 also performs a selection process for selecting an analyte (precursor ion) for the MS2 analysis. The data processing device 6 performs a first selection process or a second selection process as a selection process for selecting an analyte for the MS2 analysis based on the results of the MS1 analysis. The first selection process is a process for selecting an analyte for the MS2 analysis to be performed under one state based on the results of the most recent MS1 analysis performed under one state and feature quantities corresponding to the analyte of the most recent MS2 analysis performed under another state. On the other hand, the second selection process is a process for selecting an analysis target for an MS2 analysis to be performed under one state based on the results of the most recent MS1 analysis performed under one state, without using features corresponding to the analysis target of the most recent MS2 analysis performed under another state. Here, the "most recent analysis result" refers to the most recent analysis result obtained during the same analysis period as the MS2 analysis using the selection result of the selection process.

[0042] Hereinafter, the MS1 analysis and MS2 analysis performed under the first condition, and the MS1 analysis and MS2 analysis performed under the second condition may be referred to as the "first MS1 analysis," the "first MS2 analysis," the "second MS1 analysis," and the "second MS2 analysis," respectively. Furthermore, the spectra resulting from the first MS1 analysis, the first MS2 analysis, the second MS1 analysis, and the second MS2 analysis may be referred to as the "first MS spectrum," the "first MS / MS spectrum," the "second MS spectrum," and the "second MS / MS spectrum," respectively.

[0043] Furthermore, although the selection process for selecting positive ions is sometimes referred to as the "positive ion selection process" and the selection process for selecting negative ions is sometimes referred to as the "negative ion selection process," when there is no need to distinguish between the positive ion selection process and the negative ion selection process, they will simply be referred to as the "selection process."

[0044] Furthermore, although the first selection process for selecting positive ions may be referred to as the "first positive ion selection process," and the first selection process for selecting negative ions may be referred to as the "first negative ion selection process," when there is no need to distinguish between the first positive ion selection process and the first negative ion selection process, they will simply be referred to as the "first selection process."

[0045] Furthermore, although the second selection process for selecting positive ions may be referred to as the "second positive ion selection process," and the second selection process for selecting negative ions may be referred to as the "second negative ion selection process," when there is no need to distinguish between the second positive ion selection process and the second negative ion selection process, they will simply be referred to as the "second selection process."

[0046] 2 is a schematic diagram showing the flow of the mass spectrometry method according to the first embodiment. In the following, steps will be simply abbreviated as "S."

[0047] In S10, the data processing device 6 controls the measuring device 2 and the power supply device 4 to perform a first MS1 analysis. As a result, the data processing device 6 acquires a first MS spectrum, which is an MS spectrum of positive ions from among ions derived from components in the sample. The acquired first MS spectrum is stored in the memory 62 in association with the measurement time.

[0048] In S12, the data processing device 6 performs a second positive ion selection process. That is, the data processing device 6 selects a positive ion to be analyzed in the first MS2 analysis based on the results of the most recent first MS1 analysis, without using the selection results of the negative ion selection process. The mass-to-charge ratio indicating the selected positive ion is registered in the analysis target list as the analysis target for the first MS2 analysis. Specifically, in S12, the data processing device 6 selects an analysis target for the first MS2 analysis in S14 based on the results of the first MS1 analysis performed in S10. Note that if there is a most recent negative ion selection process that can be referenced, the data processing device 6 may perform either the first positive ion selection process or the second positive ion selection process.

[0049] In S14, the data processing device 6 controls the measurement device 2 and the power supply device 4 so that a first MS2 analysis is performed on the positive ions registered in S12 as the analysis target.

[0050] More specifically, the data processing device 6 controls the quadrupole mass filter 26 so that only ions having mass-to-charge ratios registered in the analysis target list pass through the quadrupole mass filter 26, and also controls the collision cell 27 so that the ions that have passed through the quadrupole mass filter 26 are dissociated in the collision cell 27 to generate product ions. The data processing device 6 controls each device in the second analysis chamber 204 so that positive product ions among the product ions emitted from the collision cell 27 are separated according to their mass-to-charge ratios.

[0051] As a result, the data processing device 6 acquires a first MS / MS spectrum, which is an MS / MS spectrum of a group of positive product ions among a group of product ions generated by dissociating the precursor ions for each ion having a mass-to-charge ratio registered in the analysis target list. The acquired first MS / MS spectrum is stored in the memory 62 in association with the measurement time for each mass-to-charge ratio registered in the analysis target list.

[0052] In S2, the data processing device 6 performs a first switching process to switch from the first state to the second state. More specifically, the data processing device 6 controls the power supply device 4 to switch the voltage applied to each electrode from a negative voltage to a positive voltage.

[0053] In S20, the measuring device 2 and the power supply device 4 are controlled to perform a second MS1 analysis. As a result, the data processing device 6 acquires a second MS spectrum, which is an MS spectrum of negative ions derived from the components in the sample. The acquired second MS spectrum is stored in the memory 62 in association with the measurement time.

[0054] In S22, the data processing device 6 performs a first negative ion selection process. That is, the data processing device 6 selects a negative ion to be analyzed in the second MS2 analysis based on the result of the most recent second MS1 analysis and the first feature value corresponding to the positive ion selected as the target of the most recent first MS2 analysis. The mass-to-charge ratio representing the selected negative ion is registered in the analysis target list as the target of the second MS2 analysis. Specifically, in S22, the data processing device 6 selects a target of the second MS2 analysis in S24 based on the result of the second MS1 analysis performed in S20 and the first feature value determined based on the selection result of the second positive ion selection process performed in S12.

[0055] The first feature amount indicates a negative ion that is presumed to have a common component before ionization with the selected positive ion. Therefore, the data processing device 6 can easily estimate, based on the first feature amount, which negative ion among the negative ions detected in the second MS2 analysis in the first negative ion selection process is a negative ion derived from a common component with the positive ion selected in the positive ion selection process. The first feature amount is calculated in a first feature amount calculation process that is performed at an arbitrary timing after the positive ion selection process and before the first negative ion selection process. Specifically, the data processing device 6 performs the first feature amount calculation process in S50, which is performed at an arbitrary timing after S12 and before S22.

[0056] The feature quantity corresponding to the negative ion selected as the analysis target of the most recent second MS2 analysis may be referred to as the "second feature quantity." The second feature quantity is a feature quantity indicating a positive ion that is presumed to have a common pre-ionization component with the selected negative ion. When there is no need to distinguish between the first feature quantity and the second feature quantity, they are simply referred to as the "feature quantity."

[0057] In S24, the data processing device 6 controls the measurement device 2 and the power supply device 4 to perform a second MS2 analysis using the negative ions registered in S22 as the analysis target. The control method is the same as the process of S14 except that the MS2 analysis is performed under the second control state instead of the first control state and the analysis target is different, so a description thereof will be omitted.

[0058] As a result, the data processing device 6 acquires, for each ion having a mass-to-charge ratio registered in the analysis target list, a second MS / MS spectrum which is an MS / MS spectrum of a group of negative product ions among a group of product ions generated by dissociating the ion (precursor ion). The acquired second MS / MS spectrum is stored in the memory 62 in association with the measurement time for each mass-to-charge ratio registered in the analysis target list.

[0059] In the mass spectrometer 100, a liquid sample is continuously introduced into the ion source, so that the time that a sample introduced into the mass spectrometer 100 at a given time remains within the mass spectrometer 100 is extremely short. On the other hand, the measurement waiting time associated with voltage switching and the time required for each of the positive ion selection process and negative ion selection process are extremely short. Therefore, the mass spectrometer 100 can perform a first MS1 analysis, a first MS2 analysis, a second MS1 analysis, and a second MS2 analysis on a sample introduced into the mass spectrometer 100 at a given time.

[0060] As described above, the data processing device 6 performs the first negative ion selection process in S22. In the first negative ion selection process, negative ions are selected based on both the results of the most recent second MS1 analysis and the first feature amount corresponding to the positive ions measured in the most recent first MS2 analysis. That is, among the negative ions that can be used as the analysis target of the second MS2 analysis, the negative ions to be actually used as the analysis target of the second MS2 analysis are selected based on the positive ions that were used as the analysis target of the first MS2 analysis. This allows for more selective selection of the analysis target. As a result, mass analysis of the sample can be performed more efficiently.

[0061] [First Selection Process] The first negative ion selection process will be described below as an example of the first selection process. Fig. 3 is a flowchart of the first negative ion selection process. The first negative ion selection process shown in Fig. 3 is performed by the processor 61 of the data processing device 6 executing a program stored in the memory 62.

[0062] In S221, the processor 61 reads out the most recent second MS spectrum based on the measurement time stored in association with the second MS spectrum.

[0063] In S222, the processor 61 determines whether the priority mode is set. As a method for selecting an analyte for an MS2 analysis at one polarity, the user can select either a "priority mode" in which ions corresponding to the analyte for an MS2 analysis at another polarity are preferentially selected, or an "exclusion mode" in which ions corresponding to the analyte for an MS2 analysis at another polarity are excluded from the analyte. For example, the selection of the priority mode or the exclusion mode is accepted via the input device 65. If the processor 61 determines that the priority mode is set (YES in S222), the process proceeds to S223. On the other hand, if the processor 61 determines that the priority mode is not set (NO in S222), i.e., if the processor 61 determines that the exclusion mode is set, the process proceeds to S224.

[0064] In S223, the processor 61 extracts peaks corresponding to the mass-to-charge ratios registered as first features from the peaks in the read second MS spectrum. At this time, the processor 61 may extract peaks whose signal intensities are equal to or greater than a predetermined threshold value from the peaks corresponding to the mass-to-charge ratios registered as first features. In addition to the extracted peaks, the processor 61 may further extract peaks that meet predetermined conditions.

[0065] In S224, the processor 61 extracts peaks from the read second MS spectrum other than the peaks of the mass-to-charge ratios registered as the first feature amounts. The processor 61 may extract all peaks other than the peaks of the mass-to-charge ratios registered as the first feature amounts, or may extract only peaks that meet predetermined conditions from among the peaks other than the peaks of the mass-to-charge ratios registered as the first feature amounts.

[0066] As described above, the first feature quantity is a feature quantity indicating negative ions that are presumed to have a common component before ionization with the selected positive ions. Furthermore, each peak in the second MS spectrum corresponds to a negative ion detected in the second MS1 analysis. In other words, in S223, the processor 61 extracts negative ions from the negative ions detected in the second MS1 analysis that correspond to the positive ions selected as the analysis targets for the first MS2 analysis. Furthermore, in S224, the processor 61 selects negative ions from the negative ions detected in the second MS1 analysis other than the negative ions corresponding to the positive ions selected as the analysis targets for the first MS2 analysis.

[0067] In S225, the processor 61 selects ions corresponding to each of the peaks extracted in S223 or S224 as analysis targets. More specifically, the processor 61 stores the mass-to-charge ratios of the extracted peaks in the memory 62 as an analysis target list for the second MS2 analysis.

[0068] For example, when the priority mode is selected, the processor 61 selects, as the analysis target for the second MS2 analysis, a negative ion detected in the most recent second MS1 analysis that is estimated to have a pre-ionization component common to the pre-ionization component of the positive ion being analyzed in the first MS2 analysis. In other words, when the priority mode is selected, MS2 analysis can be performed on both positive and negative ions derived from a given component. This improves the accuracy of component identification, reduces the need for additional analysis for component identification, and enables more efficient mass analysis of the sample. As a result, sample consumption and analysis time can be reduced.

[0069] Furthermore, when the exclusion mode is selected, the processor 61 selects the analytes for the second MS2 analysis from among the negative ions detected in the most recent second MS1 analysis, excluding negative ions whose pre-ionization components are estimated to be common to the pre-ionization components of the positive ions that are the analytes for the first MS2 analysis. In other words, in the exclusion mode, the analytes for the second MS2 analysis are selected so that the components that were the analytes for the first MS2 analysis are not also selected as the analytes for the second MS2 analysis. This allows for an increased number of components to be analyzed in the MS2 analysis, reducing the need for additional analysis to increase the number of components to be analyzed in the MS2 analysis and enabling more efficient mass analysis of the sample. As a result, sample consumption and analysis time can be reduced.

[0070] In this embodiment, the priority mode and the exclusion mode can be selected, but the configuration may be such that control can be performed in only one of the two modes.

[0071] Although the first negative ion selection process has been described as an example, the same process as the first negative ion selection process is also performed in the first positive ion selection process. Specifically, the first positive ion selection process is the same as the first negative ion selection process except that the MS spectrum to be read is the most recent first MS spectrum and the feature amount to be referenced is the second feature amount, and therefore a description thereof will be omitted.

[0072] [Second Selection Process] The second positive ion selection process will be described below as an example of the second selection process. Fig. 4 is a flowchart of the second positive ion selection process. The second positive ion selection process shown in Fig. 4 is performed by the processor 61 of the data processing device 6 executing a program stored in the memory 62.

[0073] In S121, the processor 61 reads out the most recent first MS spectrum based on the measurement time stored in association with the first MS spectrum.

[0074] In S122, the processor 61 extracts the top n peaks (n≧1, n is an integer) with the highest peak intensities from among the peaks in the read first MS spectrum. In addition to the extracted peaks, the processor 61 may further extract peaks that meet predetermined conditions.

[0075] In S123, the processor 61 selects ions corresponding to each of the extracted n peaks as analysis targets, and more specifically, the processor 61 stores the mass-to-charge ratios of each of the extracted n peaks in the memory 62 as an analysis target list for the first MS2 analysis.

[0076] The method for selecting the analytes in the second positive ion selection process is not limited to the above method. For example, the processor 61 may select the analytes based on the mass-to-charge ratio of the peak, or may select the analytes based on both the signal intensity and the mass-to-charge ratio of the peak. Furthermore, when the first MS2 analysis is performed multiple times, the second positive ion selection process may select the analytes in the next first MS2 analysis based on the most recently obtained first MS spectrum and the analytes in the previous first MS2 analysis. For example, the data processing device 6 may exclude the analytes in the previous first MS2 analysis from the analytes in the next first MS2 analysis.

[0077] As described above, the processor 61 selects the analytes for the first MS2 analysis based on at least one of the mass-to-charge ratio and detection intensity of the positive ions detected in the most recent first MS1 analysis, and can therefore select the analytes for the first MS2 analysis based on the abundance of components in the sample and the mass-to-charge ratio of the ions.

[0078] For example, in this embodiment, positive ions with high peak intensities are preferentially selected as the analysis target for the first MS2 analysis, so that the first MS2 analysis can be performed on components that are abundant as positive ions.

[0079] Although the second positive ion selection process has been described as an example, the second negative ion selection process also performs the same process as the second positive ion selection process. Specifically, the second negative ion selection process is the same as the second positive ion selection process except that the MS spectrum read out is the most recent second MS spectrum, and therefore a description of the second negative ion selection process will be omitted.

[0080] In the first embodiment, the ions to be analyzed in the first MS2 analysis are selected based on the peak intensities in the first MS spectrum. Therefore, it can be said that the data processing device 6 performs data dependent acquisition (DDA) mass analysis under the first state by performing steps S10 to S14.

[0081] [First Feature Calculation Process] The first feature calculation process will be described with reference to Fig. 5 and Fig. 6. Fig. 5 is a flowchart of the first feature calculation process. Fig. 6 is a diagram showing an example of a group of first feature amounts associated with one analysis target. The first feature calculation process shown in Fig. 5 is performed by the processor 61 of the data processing device 6 executing a program stored in the memory 62.

[0082] In S501, the processor 61 determines whether all mass-to-charge ratios registered in the analysis target list have been processed. The analysis target list referenced in S501 is the analysis target list created in the most recent positive ion selection process, and is the most recent analysis target list in which the mass-to-charge ratios of the positive ions selected as the analysis targets for the first MS2 analysis are registered. If it is determined that processing has been performed (YES in S501), the processor 61 terminates the first correspondence list creation process. If it is determined that processing has not been performed (NO in S501), that is, if there are unprocessed mass-to-charge ratios, the processor 61 performs the processes from S502 onwards.

[0083] In S502, the processor 61 reads the raw mass-to-charge ratios from the analysis target list.

[0084] In S503, the processor 61 determines the charge and calculates the exact mass of the positive ion selected as the analysis target from the read-out mass-to-charge ratio. The charge (charge) of the read-out mass-to-charge ratio is determined based on the results of the first MS1 analysis referenced in the positive ion selection process. For example, the charge is determined based on the isotope peak width derived from the component corresponding to the peak of the read-out mass-to-charge ratio. Note that the method for determining the charge is not limited to this method, and any method known to those skilled in the art can be used. The exact mass of the positive ion selected as the analysis target in the most recent first MS2 analysis is calculated by multiplying the read-out mass-to-charge ratio by the determined charge.

[0085] In S504, the processor 61 determines candidates for the accurate mass of the component before ionization of the positive ion corresponding to the read mass-to-charge ratio based on the charge number obtained as the determination result and the first candidate list. The first candidate list registers the types of adducted ions and desorbed ions corresponding to the positive ions, as well as charge number information. The type of ion that adducts to a component in a sample to form a positive ion, or the type of ion that desorbs from a component in a sample to form a positive ion, can be estimated based on the solvent and ionization method used. The adducted ions and desorbed ions may be registered by the user via the input device 65 or by the processor 61 based on the measurement conditions. The charge number information is information related to charge number, and includes, for example, information indicating the charge number of the registered ion and information indicating the possible charge number of the positive ion. The information indicating the possible charge number of the positive ion includes the range of possible charge numbers of the positive ion, the number of added or desorbed ions, etc.

[0086] The processor 61 extracts candidate combinations of adduct ions and desorbed ions based on the adduct ions and desorbed ions registered in the first candidate list so that the valence is the result of the determination. The processor 61 calculates candidate accurate masses of the components before ionization by subtracting the total mass of the adduct ions included in the extracted candidate combinations from the exact mass of the positive ion to be analyzed, or by adding the total mass of the desorbed ions included in the extracted candidate combinations to the exact mass of the positive ion to be analyzed.

[0087] For example, if the obtained valence is +2 and two types of adduct ions, the first adduct ion and the second adduct ion, are registered as +1 adduct ions in the first candidate list, three candidates are extracted as combination candidates: two first adduct ions, two second adduct ions, and one first adduct ion and one first diadduct ion.

[0088] When the number of ions added or desorbed for each type of ion is registered in the first candidate list as valence information, candidates are extracted as follows: For example, if the obtained valence is +2 and two types of +1 adduct ions, the first adduct ion and the second adduct ion, are registered in the first candidate list, and each ion has a number of 2 added, two candidates, two first adduct ions and two second adduct ions, are extracted as combination candidates.

[0089] In step S505, the processor 61 determines the accurate mass of a negative ion corresponding to each candidate of the accurate mass of the pre-ionized component based on the second candidate list. The negative ion corresponding to the positive ion is a negative ion that is estimated to have a common pre-ionized component with the pre-ionized component of the positive ion.

[0090] The second candidate list contains registered information on the types of adducted ions and desorbed ions corresponding to the negative ions, as well as valence information. As with positive ions, the type of ion that adducts to a component in a sample to become a negative ion, or the type of ion that desorbs from a component in a sample to become a negative ion, can be estimated based on the solvent and ionization method used. The adducted ions and desorbed ions may be registered by the user via the input device 65, or may be registered by the processor 61 based on the measurement conditions. The valence information is information related to valence, and includes, for example, information indicating the valence of the registered ions and information indicating the possible valences of the negative ions. The information indicating the possible valences of the negative ions includes the range of valences that the negative ions can have, the number of ions that are added or desorbed, etc.

[0091] The processor 61 extracts candidate combinations of adduct ions and desorbed ions based on the second candidate list so that the negative ions indicated by the valence information have possible valences. For each candidate accurate mass of a component before ionization, the processor 61 adds the total mass of the adduct ions included in the extracted candidate combination to the accurate mass of the component, or subtracts the total mass of the desorbed ions included in the extracted candidate combination from the accurate mass of the component, thereby determining a candidate accurate mass of the negative ion corresponding to the positive ion.

[0092] For example, consider a case where the range of valences that negative ions can take is registered as 1 to 2 in the second candidate list, and two types of +1 adduct ions, the first adduct ion and the second adduct ion, are registered. In this case, five combination candidates are extracted: one first adduct ion, one second adduct ion, two first adduct ions, two second adduct ions, and one first adduct ion and one first diadduct ion.

[0093] In addition, when the number of ions added or desorbed for each type of ion is registered in the second candidate list as valence information, candidates are extracted as follows, for example. For example, consider a case where 1 to 2 is registered as the range of valence that negative ions can take, two types of +1 adduct ions, a first adduct ion and a second adduct ion, are registered, and the number of additions is registered as 1 for the first adduct ion and 2 for the second adduct ion. In this case, two candidates are extracted as combination candidates: one first adduct ion and two second adduct ions.

[0094] In step S506, the processor 61 calculates the mass-to-charge ratio of each candidate negative ion based on the charge information of each ion. For example, if the exact mass of a negative ion is calculated in step S505 assuming that a doubly charged negative ion has been added, the processor 61 divides the calculated exact mass by 2 to calculate the mass-to-charge ratio.

[0095] In S507, the processor 61 registers the determined mass-to-charge ratio as the first feature amount, and returns to S501.

[0096] After performing the processes of S502 to S507 for all mass-to-charge ratios registered in the analysis target list, the processor 61 ends the first feature calculation process.

[0097] 6, it is assumed that a positive ion having a mass-to-charge ratio of A is registered in the analysis target list. In this case, the processor 61 determines the charge number by calculating the isotope peak width derived from the component corresponding to the peak having the mass-to-charge ratio A based on the first MS spectrum referenced when the analysis target list was created. The accurate mass number Ax of the positive ion having the mass-to-charge ratio A is calculated by multiplying the mass-to-charge ratio A by the charge number x, which is the determination result.

[0098] Assuming that a positive ion with a mass-to-charge ratio A is an ion derived from compound X in a sample, the positive ion is an ion in which an ion with a valence of x is added to or desorbed from compound X.

[0099] 6 , it is assumed that adduct ions with mass numbers a and b are registered in the first candidate list as ions with valence x. In this case, the processor 61 obtains candidates for the exact mass number of compound X by subtracting the mass number a or the mass number b from the exact mass number Ax. Specifically, two candidates, Ax-a and Ax-b, are obtained as candidates for the exact mass number of compound X. Note that if a desorbed ion is registered, the candidate for the exact mass number of compound X is obtained by adding the mass number of the desorbed ion to the exact mass number Ax.

[0100] In the example shown in FIG. 6 , y and z are registered as possible valences of negative ions in the second candidate list, and two types of adduct ions (an adduct ion with valence y and mass number c, and an adduct ion with valence z and mass number d) are registered. In this case, the processor 61 extracts two candidate combinations: one adduct ion with mass number c and one adduct ion with mass number d. The processor 61 adds mass number c or mass number d to each candidate exact mass number of compound X to determine the exact mass number of the negative ion when compound X is ionized into a negative ion. Specifically, four candidates for the exact mass number of the negative ion of compound X are obtained: (Ax-a)+c, (Ax-a)+d, (Ax-b)+c, and (Ax-b)+d. Note that if a desorbed ion is registered, the exact mass number of the negative ion derived from compound X is determined by subtracting the mass number of the desorbed ion from each candidate exact mass number of compound X.

[0101] The processor 61 divides the determined exact mass number of the negative ion by the valence to determine the mass-to-charge ratio of the negative ion derived from compound X. Specifically, four candidates for the mass-to-charge ratio are determined: [(Ax-a)+c] / y, [(Ax-a)+d] / z, [(Ax-b)+c] / y, and [(Ax-b)+d] / z.

[0102] That is, by performing S501 to S507, the processor 61 estimates the mass-to-charge ratio of the pre-ionization components of the positive ions to be analyzed in the first MS2 analysis and the negative ions that have a common pre-ionization component.

[0103] The processor 61 only needs to be able to estimate at what position in the second MS spectrum a peak will appear when a negative ion that has a common pre-ionization component to a positive ion is measured, and may estimate the time of flight corresponding to the mass-to-charge ratio instead of the mass-to-charge ratio.

[0104] As described above, the first feature quantity indicating the negative ion corresponding to the positive ion is calculated by taking into consideration the valence and the adduct ion or desorbed ion, and therefore, it is possible to more accurately estimate the negative ion that has the same pre-ionization components as the positive ion.

[0105] Although the first feature calculation process has been described as an example, the second feature calculation process for obtaining the second feature is similar to the first feature calculation process. Specifically, the second feature calculation process is common to the first feature calculation process except for the following points. First, the second feature calculation process differs from the first feature calculation process in that it obtains feature quantities corresponding to positive ions that are estimated to have components common to the pre-ionization components of the selected negative ions. Second, the second feature calculation process differs from the first feature calculation process in that the analyte list referenced is the analyte list created in the most recent negative ion selection process, which is the most recent analyte list in which the mass-to-charge ratio of the negative ion selected as the analyte for the second MS2 analysis is registered. Third, the second feature calculation process differs from the first feature calculation process in that it references a second candidate list in S504. Fourth, the second feature calculation process differs from the first feature calculation process in that it references a first candidate list in S505.

[0106] In the above embodiment, the first and second candidate lists are registered in advance with the valence number for each ion (adduct ion and desorbed ion). The valence numbers may be registered separately from the adduct ions and desorbed ions. In this case, in S504, the processor 61 may subtract or add the masses of the adduct ions and desorbed ions registered in the first candidate list according to the valence number determined in S503, thereby determining candidates for the accurate mass of the components before ionization.

[0107] Similarly, in S505 and S506, the processor 61 may comprehensively determine mass-to-charge ratio candidates of negative ions for each registered charge state for each adduct ion and desorbed ion. For example, if there are three candidates for the accurate mass of the component before ionization, three adduct ions and three desorbed ions (all of which are monovalent ions) registered in the second candidate list, and the registered charge states range from monovalent to trivalent, then 57 (=3×19) candidates for mass-to-charge ratio of negative ions will be found.

[0108] Second Embodiment [Overview of Mass Analysis Method] In the first embodiment, the data processing device 6 performs the first MS1 analysis and the first MS2 analysis, followed by the second MS1 analysis and the second MS2 analysis. The data processing device 6 may also control the measurement device 2 and the power supply device 4 to repeatedly perform the first MS1 analysis, the first MS2 analysis, the second MS1 analysis, and the second MS2 analysis. FIG. 7 is a schematic diagram showing the flow of the mass analysis method according to the second embodiment. Description of the processing steps common to the mass analysis method according to the first embodiment will be omitted. The mass analysis device used in the mass analysis method according to the second embodiment is common to the mass analysis device 100 according to the first embodiment, and therefore description thereof will be omitted.

[0109] After performing S10 to S24 described in the first embodiment, the data processing device 6 performs S26 to S38, and then repeatedly performs S2 to S38.

[0110] In S26, the data processing device 6 performs a second negative ion selection process. That is, the data processing device 6 selects a negative ion to be analyzed in the second MS2 analysis based on the results of the most recent second MS1 analysis without using the first feature. The mass-to-charge ratio indicating the selected negative ion is registered in the analysis target list as the analyte for the second MS2 analysis. Specifically, in S26, the data processing device 6 selects an analyte for the second MS2 analysis in S28 based on the results of the second MS1 analysis performed in S20. The mass-to-charge ratio indicating the selected analyte is registered in the analysis target list as the analyte for the second MS2 analysis in S28. Note that the data processing device 6 may select an analyte for S28 in S26 so as to exclude the analyte for the second MS2 analysis in S24.

[0111] In S28, the data processing device 6 controls the measurement device 2 and the power supply device 4 to perform a second MS2 analysis using the negative ions registered in S26 as the analysis target. The control method is the same as the process in S24 except for the different analysis target, and therefore a description thereof will be omitted. This allows the data processing device 6 to acquire a second MS / MS spectrum of the negative ions derived from the abundant components. The acquired second MS / MS spectrum is stored in the memory 62 in association with the measurement time for each mass-to-charge ratio registered as the analysis target list.

[0112] In S3, the data processing device 6 performs a second switching process to switch from the second state to the first state. More specifically, the data processing device 6 controls the power supply device 4 to switch the voltage applied to each electrode from a positive voltage to a negative voltage.

[0113] In S30, the data processing device 6 controls the measuring device 2 and the power supply device 4 to perform a first MS1 analysis. As a result, the data processing device 6 acquires a first MS spectrum. The acquired first MS spectrum is stored in the memory 62 in association with the measurement time.

[0114] In S32, the data processing device 6 performs a first positive ion selection process. That is, the data processing device 6 selects a positive ion to be analyzed in the first MS2 analysis based on the result of the most recent first MS1 analysis and the second feature amount corresponding to the negative ion selected as the analyte of the most recent second MS1 analysis. The mass-to-charge ratio indicating the selected positive ion is registered in the analysis target list as the analyte of the first MS2 analysis. Specifically, in S32, the data processing device 6 selects an analyte of the first MS2 analysis in S34 based on the result of the first MS1 analysis performed in S30 and the second feature amount determined based on the selection result of the second negative ion selection process performed in S26. The mass-to-charge ratio indicating the selected analyte is registered in the analysis target list as the analyte of the first MS2 analysis in S34.

[0115] The second feature amount is calculated in a second feature amount calculation process that is performed at an arbitrary timing after the negative ion selection process and before the first positive ion selection process. Specifically, the data processing device 6 performs the second feature amount calculation process in S60, which is performed at an arbitrary timing after S26 and before S32.

[0116] In S34, the data processing device 6 controls the measurement device 2 and the power supply device 4 to perform a first MS2 analysis using the positive ions registered in S32 as the analysis target. This allows the data processing device 6 to acquire a first MS / MS spectrum of a positive ion that corresponds to the negative ion that was the analysis target in S28, or a positive ion other than the positive ion that corresponds to the negative ion that was the analysis target in S28, among the positive ions that can be used as the analysis target in the first MS2 analysis. The acquired first MS / MS spectrum is stored in memory 62 in association with the measurement time for each mass-to-charge ratio registered in the analysis target list.

[0117] In S36, the data processing device 6 performs a second positive ion selection process. Specifically, in S36, the data processing device 6 selects an analyte for the first MS2 analysis in S38 based on the results of the first MS1 analysis performed in S30. The mass-to-charge ratio indicating the selected analyte is registered in the analyte list as the analyte for the first MS2 analysis in S38. Note that in S36, the data processing device 6 may select an analyte for S38 so as to exclude the analyte for the first MS2 analysis in S34.

[0118] In S38, the data processing device 6 controls the measurement device 2 and the power supply device 4 to perform a first MS2 analysis using the positive ions registered in S36 as the analysis target. This allows the data processing device 6 to acquire a first MS / MS spectrum of the positive ions derived from the abundant component. The acquired first MS / MS spectrum is stored in the memory 62 in association with the measurement time for each mass-to-charge ratio registered as the analysis target list.

[0119] Thereafter, the data processing device 6 repeatedly performs S2 to S38 until the set analysis time has elapsed. That is, the data processing device 6 performs S10 to S14, and then repeatedly performs S2 to S38. The numbers in parentheses in the figure indicate the number of cycles from the second cycle onwards. For example, S22(2) indicates S22 in the second cycle. In S22(2), the data processing device 6 determines the analysis target for the second MS2 analysis based on the analysis result of the second MS1 analysis obtained in S20(2) and the selection result of the first selection process (S36 in FIG. 7) performed in the previous cycle.

[0120] The data processing device 6 performs a second negative ion selection process that selects analysis targets from a different perspective than the first negative ion selection process and the first negative ion selection process. By performing S24 and S28, the data processing device 6 can perform a second MS2 analysis on negative ions selected from different perspectives. Therefore, the number of types of negative ions to be analyzed in the second MS2 analysis can be increased compared to when only the negative ions selected in the first negative ion selection process are analyzed.

[0121] Furthermore, the data processing device 6 performs steps S24 and S28 without switching to the first state. This allows the measurement interval between steps S24 and S28 to be shortened. As a result, the second MS2 analysis can be performed on various types of negative ions derived from a sample introduced into the measurement device 2 at a certain timing.

[0122] Furthermore, the data processing device 6 refers to the results of the second MS1 analysis, which are common to both the first negative ion selection process performed in S22 and the second negative ion selection process performed in S26. Therefore, since it is not necessary to perform the second MS1 analysis for each selection process, it is not necessary to increase the number of times the second MS1 analysis is performed. Therefore, even if the number of selection processes is increased, the frequency of the second MS2 analysis does not decrease. In other words, since the number of analytes in the second MS2 analysis can be increased by using different selection processes, the frequency of the second MS2 analysis can be maintained, thereby obtaining more analysis results.

[0123] Furthermore, by performing steps S2 to S28, the data processing device 6 can comprehensively perform a second MS2 analysis on ions that can be measured under the second state. Similarly, by performing steps S3 to S38, the data processing device 6 can comprehensively perform a first MS2 analysis on ions that can be measured under the first state.

[0124] For example, when the priority mode is selected, the data processing device 6 performs S10 to S14 or S30, S36, and S38 to perform a first MS2 analysis on components abundant as positive ions. The data processing device 6 performs S20 to S24 to further perform a second MS2 analysis on components abundant as positive ions. Similarly, the data processing device 6 performs S20, S26, and S28 to further perform a second MS2 analysis on components abundant as negative ions. The data processing device 6 performs S30 to S34 to further perform a first MS2 analysis on components abundant as negative ions. That is, by repeating the processes of S2 to S38, the data processing device 6 performs the first and second MS2 analyses on components abundant as positive ions, and the first and second MS2 analyses on components abundant as negative ions.

[0125] Third Embodiment Another embodiment of a mass spectrometry method in which a first MS1 analysis, a first MS2 analysis, a second MS1 analysis, and a second MS2 analysis are repeatedly performed will be described. Fig. 8 is a schematic diagram showing the flow of the mass spectrometry method according to the third embodiment. Note that a description of processing steps common to the mass spectrometry methods according to the first and second embodiments will be omitted. Furthermore, the mass spectrometry apparatus used in the mass spectrometry method according to the third embodiment is common to the mass spectrometry apparatus 100 according to the first embodiment, and therefore a description thereof will be omitted.

[0126] After performing S10 to S24 described in the first embodiment, the data processing device 6 performs S25 to S34, and thereafter repeats the processing of S10 to S34.

[0127] In S25, the data processing device 6 controls the measuring device 2 and the power supply device 4 to perform a second MS1 analysis. As a result, the data processing device 6 acquires a second MS spectrum. The acquired second MS spectrum is stored in the memory 62 in association with the measurement time. That is, after performing the second MS1 analysis in S20, the data processing device 6 performs the second MS1 analysis again in S25 without switching to the first state.

[0128] In S26, the data processing device 6 performs a second negative ion selection process. Specifically, in S26, the data processing device 6 selects an analyte for the second MS2 analysis in S28 based on the results of the second MS1 analysis performed in S25. The mass-to-charge ratio indicating the selected analyte is registered in the analyte list as the analyte for the second MS2 analysis in S28. Note that in S26, the data processing device 6 may select an analyte for S28 so as to exclude the analyte for the second MS2 analysis in S24.

[0129] After performing S26, the data processing device 6 performs S28 to S34, similar to the mass spectrometry method according to the second embodiment. The data processing device 6 then repeats the processes of S10 to S34 until the set analysis time expires. The numbers in parentheses in the figure indicate the number of cycles from the second round onward. For example, S22(2) indicates S22 in the second round.

[0130] In the third embodiment, the ions to be analyzed in the second MS2 analysis are selected based on the peak intensity in the second MS spectrum. Therefore, by performing steps S25 to S26, the data processing device 6 can be said to be performing data dependent acquisition (DDA) mass analysis under the second state.

[0131] The data processing device 6 performs a second negative ion selection process that selects analysis targets from a different perspective than the first negative ion selection process and the first negative ion selection process. By performing S24 and S28, the data processing device 6 can perform a second MS2 analysis on negative ions selected from different perspectives. Therefore, the number of components that can be analyzed in the second MS2 analysis can be increased compared to when only negative ions selected in the first negative ion selection process are analyzed.

[0132] Furthermore, by performing S24 and S28 without switching to the first state, the data processing device 6 can perform a second MS2 analysis on various types of negative ions derived from a sample introduced into the measuring device 2 at a certain timing.

[0133] Furthermore, samples are continuously introduced into the mass spectrometer 100, and measurement results change over time. Therefore, if the measurement interval between an MS2 analysis and an MS1 ​​analysis referenced to determine the analyte of the MS2 analysis becomes long, the abundance of the precursor ion of the analyte may change between the MS2 analysis and the MS1 analysis. Furthermore, there is a risk that a precursor ion generated in the MS1 analysis may not be generated and therefore cannot be extracted in the MS2 analysis. Therefore, it is preferable that the measurement interval between the MS2 analysis and the MS1 analysis referenced to determine the analyte of the MS2 analysis be short.

[0134] According to the mass spectrometry method of the third embodiment, the second MS1 analysis is performed twice without switching to the first state, and the results of different second MS1 analyses are referenced in the first negative ion selection process performed in S22 and the second negative ion selection process performed in S26. Therefore, an analysis schedule can be created for the second MS1 analysis, negative ion selection process, and second MS2 analysis as a set, as in S20 to S24 and S25 to S28. As a result, the measurement interval between the second MS1 analysis and the second MS2 analysis can be shortened.

[0135] Furthermore, by performing S10 to S34, the data processing device 6 can comprehensively perform the second MS2 analysis on ions that can be measured under the second state, and can also comprehensively perform the first MS2 analysis on ions that can be measured under the first state.

[0136] For example, when the priority mode is selected, the data processing device 6 performs steps S10 to S14 to perform a first MS2 analysis on components abundant as positive ions. The data processing device 6 performs steps S20 to S24 to perform a second MS2 analysis on components abundant as positive ions. Similarly, the data processing device 6 performs steps S25 to S28 to perform a second MS2 analysis on components abundant as negative ions. The data processing device 6 performs steps S30 to S34 to perform a first MS2 analysis on components abundant as negative ions. That is, by repeating the processes of steps S10 to S34, the data processing device 6 performs the first and second MS2 analyses on components abundant as positive ions, and the first and second MS2 analyses on components abundant as negative ions.

[0137] Fourth Embodiment Another embodiment of a mass spectrometry method in which a first MS1 analysis, a first MS2 analysis, a second MS1 analysis, and a second MS2 analysis are repeatedly performed will be described. Fig. 9 is a schematic diagram showing the flow of the mass spectrometry method according to the fourth embodiment. Note that a description of processing steps common to the first embodiment will be omitted. Furthermore, the mass spectrometry apparatus used in the mass spectrometry method according to the fourth embodiment is common to the mass spectrometry apparatus 100 according to the first embodiment, and therefore a description thereof will be omitted.

[0138] After executing S10 to S24 described in the first embodiment, the data processing device 6 executes S3 to switch from the second state to the first state, and then repeats the processes of S10 to S3. This allows the first MS1 analysis, the first MS2 analysis, the second MS1 analysis, and the second MS2 analysis to be performed consecutively on samples that are continuously introduced into the mass spectrometer 100.

[0139] For example, when the exclusion mode is selected, the processes of S10 to S24 are repeated to comprehensively perform MS2 analysis on components that tend to become positive ions and components that tend to become negative ions. In particular, when the exclusion mode is selected, negative ions corresponding to the analyte ions in the first MS2 analysis are excluded from the analytes in the second MS2 analysis. This allows MS2 analysis to be performed on a larger number of components.

[0140] Fifth Embodiment Another embodiment of a mass spectrometry method in which a first MS1 analysis, a first MS2 analysis, a second MS1 analysis, and a second MS2 analysis are repeatedly performed will be described. Fig. 10 is a schematic diagram showing the flow of the mass spectrometry method according to the fifth embodiment. Note that a description of the processing steps common to the first and second embodiments will be omitted. Furthermore, the mass spectrometer used in the mass spectrometry method according to the fifth embodiment is the same as the mass spectrometer 100 according to the first embodiment, and therefore a description thereof will be omitted.

[0141] After executing S10 to S24 described in the first embodiment, the data processing device 6 executes S3 to switch from the second state to the first state and executes S0 to S34, and then repeatedly executes S2 to S34. The mass spectrometry method according to the fifth embodiment differs from the mass spectrometry method according to the third embodiment in that S25 to S28 are not executed and S10 to S14 are not executed from the second round onwards.

[0142] Unlike the third embodiment, the data processing device 6 according to the fifth embodiment does not execute steps S25 to S8, and therefore in the first positive ion selection process in S32, an analyte for the first MS2 analysis in S34 is selected based on the result of the first MS1 analysis performed in S30 and the second feature amount determined based on the selection result of the first negative ion selection process performed in S22. That is, the data processing device 6 according to the fifth embodiment selects an analyte for the next first MS2 analysis based on the analyte for the second MS2 analysis selected based on the analyte for the previous first MS2 analysis.

[0143] Similarly, because steps S10 to S14 are not executed from the second cycle onward, the data processing device 6 according to the fifth embodiment selects, in the second selection process in S22(2), an analyte for the second MS2 analysis in S24(2) based on the result of the second MS1 analysis performed in S20(2) and the first feature amount determined based on the selection result of the first positive ion selection process performed in S32 of the immediately preceding cycle. That is, the data processing device 6 according to the fifth embodiment selects an analyte for the next second MS2 analysis based on the analyte for the first MS2 analysis selected based on the analyte for the previous second MS2 analysis.

[0144] Therefore, the target of MS2 analysis can be selected with higher selectivity, and as a result, mass analysis of the sample can be performed more efficiently.

[0145] For example, when the exclusion mode is selected, the mass spectrometry method according to the fifth embodiment can comprehensively perform MS2 analysis on components that tend to become positive ions and components that tend to become negative ions. In the mass spectrometry method according to the fifth embodiment, in S32, components that tend to become positive ions and that were not selected as the analysis targets in the second MS2 analysis are selected as the analysis targets. Furthermore, in S22(2), components that tend to become negative ions and that were not selected as the analysis targets in the first MS2 analysis are selected as the analysis targets. Therefore, the mass spectrometry method according to the fifth embodiment can efficiently perform MS2 analysis on a greater variety of components.

[0146] In the mass spectrometry methods according to the first to fifth embodiments, an example has been shown in which the analysis schedule is set up to start with the measurement of positive ions, but the analysis schedule may also be set up to start with the measurement of negative ions. That is, in the present disclosure, the "first ions having a first polarity" are described as positive ions and the "second ions having a second polarity" are described as negative ions, but the "first ions" may be negative ions and the "second ions" may be positive ions.

[0147] [Aspects] It will be understood by those skilled in the art that the above-described embodiments are specific examples of the following aspects.

[0148] (Item 1) A mass spectrometry method according to one aspect uses a mass spectrometer capable of performing MS analysis, in which a group of ions obtained by ionizing a sample are subjected to mass analysis, and MS / MS analysis, in which a group of ions obtained by fragmenting selected ions from the group of ions obtained by ionizing the sample are subjected to mass analysis. The mass spectrometer is capable of performing MS analysis and MS / MS analysis under two conditions: a first condition for detecting first ions having a first polarity, and a second condition for detecting second ions having a second polarity opposite to the first polarity. The mass spectrometry method includes the steps of: performing a first MS analysis under a first state; performing a first ion selection process to select first ions to be analyzed based on the results of the first MS analysis; performing a first MS / MS analysis under the first state using the first ions selected in the first ion selection process as the analysis targets; switching from the first state to a second state; performing a second MS analysis under the second state; performing a second ion selection process to select second ions to be analyzed based on the results of the second MS analysis; and performing a second MS / MS analysis under the second state using the second ions selected in the second ion selection process as the analysis targets. The step of performing the second ion selection process includes a first selection process to select second ions to be analyzed based on the results of the second MS analysis and a first feature corresponding to the selected first ions. The step of performing the second MS / MS analysis includes a second MS / MS analysis using the second ions selected in the first selection process as the analysis targets.

[0149] According to the mass spectrometry method described in paragraph 1, the second ions to be analyzed in the second MS / MS analysis are selected based on the results of the second MS analysis and the feature quantities corresponding to the first ions to be analyzed in the first MS / MS analysis, thereby enabling the selection of the analytes with higher selectivity, thereby enabling more efficient mass analysis of the sample.

[0150] (2) In the mass spectrometry method described in (1), the first feature is a feature indicating a second ion that is estimated to have a pre-ionization component common to the pre-ionization component of the selected first ion.

[0151] According to the mass spectrometry method described in paragraph 2, it is possible to easily estimate, based on the first feature, which of the second ions detected in the second MS analysis is an ion derived from a component common to the selected first ion.

[0152] (Clause 3) In the mass analysis method described in paragraph 2, the step of performing the first selection process includes a step of selecting, from among the second ions detected in the second MS analysis, second ions corresponding to the first characteristic amount as second ions to be analyzed.

[0153] According to the mass spectrometry method described in paragraph 3, a second ion derived from a component common to the first ion that is the target of the first MS / MS analysis is selected as the target of the second MS / MS analysis. In other words, for a given component in a sample, MS / MS analysis can be performed on both the first ion and the second ion derived from that component. This improves the accuracy of component identification, reduces the need for additional analysis for component identification, and enables more efficient mass analysis of the sample. As a result, sample consumption can be reduced and analysis time can be shortened.

[0154] (4) In the mass spectrometry method described in paragraph 2 or 3, the step of performing the first selection process includes a step of selecting second ions to be analyzed from among the second ions detected in the second MS analysis, other than the second ions corresponding to the first feature amount.

[0155] According to the mass spectrometry method described in paragraph 4, the analytes for the second MS / MS analysis are selected from the second ions excluding the second ions derived from components common to the first ions that are the analytes for the first MS / MS analysis. That is, the analytes for the second MS / MS analysis are selected so that the components that were the analytes for the first MS / MS analysis are not also the analytes for the second MS / MS analysis. This allows for an increase in the number of components that can be analyzed in the MS / MS analysis, reducing the need for additional analysis to increase the number of components that can be analyzed in the MS / MS analysis, and enabling more efficient mass analysis of samples. As a result, sample consumption can be reduced and analysis time can be shortened.

[0156] (5) The mass spectrometry method described in any one of paragraphs 2 to 4 further includes the steps of: determining the valence of the selected first ion based on the results of a first MS analysis referenced in the first ion selection process; estimating the exact mass of a specific component before ionization of the selected first ion based on the determined valence and a first ion candidate including at least one of an ion that generates the first ion by adding to a component in the sample and an ion that generates the first ion by desorbing from the component in the sample; and obtaining a first feature amount indicating a second ion estimated to be generated by ionizing the specific component based on the estimated exact mass of the specific component and a second ion candidate including at least one of an ion that generates a second ion by adding to a component in the sample and an ion that generates the second ion by desorbing from the component in the sample.

[0157] According to the mass spectrometry method described in paragraph 5, the first feature quantity indicating the second ion that is estimated to have a common component before ionization with the component of the selected first ion is calculated taking into consideration the charge state and the ions attached to or desorbed from the component, thereby making it possible to more accurately estimate the second ion that has a common component before ionization with the component of the selected first ion.

[0158] (Item 6) In the mass spectrometry method described in any one of Items 1 to 5, the step of performing a single ion selection process includes a step of selecting a first ion to be analyzed based on at least one of information on the mass-to-charge ratio and the detection intensity of the first ion detected in the first MS analysis.

[0159] According to the mass spectrometry method described in item 6, the first ions to be analyzed can be selected based on the mass-to-charge ratio of the first ions or the abundance of the components in the sample.

[0160] (Item 7) In the mass spectrometry method according to any one of Items 1 to 6, the step of performing the second ion selection process further includes a second selection process of selecting the second ions to be analyzed based on at least one of information on the mass-to-charge ratio and the detection intensity of the second ions detected in the second MS analysis, without using the first feature amount. The step of performing the second MS / MS analysis further includes a step of performing a second MS / MS analysis using the second ions selected in the second selection process as the analysis target.

[0161] According to the mass spectrometry method described in paragraph 7, the first selection process and the second selection process are performed to select the analysis target from a different perspective than the first selection process. Therefore, the number of types of second ions to be analyzed in the second MS / MS analysis can be increased compared to when only the second ions selected in the first selection process are analyzed.

[0162] (Item 8) In the mass analysis method described in Item 7, the step of performing a second MS / MS analysis using the second ions selected in the first selection process as the analysis target, and the step of performing a second MS / MS analysis using the second ions selected in the second selection process as the analysis target are performed without switching to the first state.

[0163] According to the mass spectrometry method described in paragraph 8, it is possible to shorten the measurement interval between the second MS / MS analysis in which the second ions selected in the first selection process are the analysis target and the second MS / MS analysis in which the second ions selected in the second selection process are the analysis target, thereby making it possible to perform the second MS / MS analysis on various types of second ions derived from a sample introduced into the mass spectrometer at a certain timing.

[0164] (Item 9) In the mass spectrometry method described in Item 8, the results of the second MS analysis referred to in the first selection process and the results of the second MS analysis referred to in the second selection process are common.

[0165] According to the mass spectrometry method described in paragraph 9, there is no need to perform the second MS analysis for each selection process, and therefore there is no need to increase the number of times the second MS analysis is performed, and the frequency of the second MS / MS analysis does not decrease even if the number of selection processes is increased. In other words, the number of types of analytes in the second MS / MS analysis can be increased by using different selection processes, while maintaining the frequency of the second MS / MS analysis, thereby enabling more analysis results to be obtained.

[0166] (Item 10) In the mass spectrometry method described in Item 8, the step of performing the second MS analysis includes a step of performing the second MS analysis after switching from the first state to the second state, and a step of performing the second MS analysis again without switching to the first state after the second MS analysis performed after switching to the second state. The result of the second MS analysis referred to in the first selection process and the result of the second MS analysis referred to in the second selection process are different.

[0167] If the measurement interval between the second MS / MS analysis and the second MS analysis referenced to determine the analyte of the second MS / MS analysis is long, the abundance of the precursor ion of the analyte may change between the time when the second MS / MS analysis is performed and the time when the second MS / MS analysis is performed. Furthermore, there is a risk that a precursor ion generated in the second MS analysis may not be generated and therefore cannot be extracted in the second MS / MS analysis. Therefore, it is preferable that the measurement interval between the second MS / MS analysis and the second MS analysis referenced to determine the analyte of the second MS / MS analysis is short. According to the mass spectrometry method described in paragraph 10, different second MS analysis results are referenced in the first selection process and the second selection process, so that an analysis schedule can be created that includes the second MS analysis, the selection process, and the second MS / MS analysis as a single set. As a result, the measurement interval between the second MS analysis and the second MS / MS analysis can be shortened.

[0168] (Item 11) In the mass spectrometry method according to any one of Items 1 to 10, the step of performing the first MS analysis includes a step of performing the first MS analysis after switching from the second state to the first state. The step of performing the first ion selection process includes a step of selecting a first ion to be analyzed based on a result of the first MS analysis performed after switching to the first state and a second feature amount corresponding to the second ion selected in the first selection process.

[0169] According to the mass spectrometry method described in paragraph 11, a first ion to be analyzed in a first MS / MS analysis can be selected based on a second feature quantity corresponding to a second ion to be analyzed in a second MS / MS analysis, which second ion is selected based on a first feature quantity corresponding to a first ion to be analyzed in a first MS / MS analysis. This allows for more selective selection of the ion to be analyzed in the first MS / MS analysis. As a result, mass analysis of a sample can be performed more efficiently.

[0170] (Item 12) A mass spectrometer according to one aspect is capable of performing MS analysis, which performs mass analysis on a group of ions obtained by ionizing a sample, and MS / MS analysis, which performs mass analysis on a group of ions obtained by fragmenting selected ions from the group of ions obtained by ionizing the sample. The mass spectrometer includes a measurement unit having a mass separation unit that separates ions according to their mass-to-charge ratios, a power supply unit that applies a voltage to the mass separation unit, and a controller that controls the measurement unit and the power supply unit. The mass spectrometer is capable of performing MS analysis and MS / MS analysis under two states: a first state in which first ions having a first polarity are detected, and a second state in which second ions having a second polarity opposite to the first polarity are detected. The controller controls the measurement unit and power supply unit to perform a first MS analysis under a first state, performs a first ion selection process to select first ions to be analyzed based on the results of the first MS analysis, controls the measurement unit and power supply unit to perform a first MS / MS analysis under the first state using the first ions selected in the first ion selection process as the analysis target, controls the power supply unit to switch from the first state to the second state to apply a voltage to the mass separation unit, controls the measurement unit and power supply unit to perform a second MS analysis under the second state, performs a second ion selection process to select second ions to be analyzed based on the results of the second MS analysis, and controls the measurement unit and power supply unit to perform a second MS / MS analysis under the second state using the second ions selected in the second ion selection process as the analysis target. The step of performing the second ion selection process includes a step of performing a first selection process to select second ions to be analyzed based on the results of the second MS analysis and a first feature amount corresponding to the selected first ions. The step of performing the second MS / MS analysis includes a step of performing the second MS / MS analysis on the second ions selected in the first selection process as the analysis target.

[0171] According to the mass spectrometer described in paragraph 12, the second ions to be analyzed in the second MS / MS analysis are selected based on the results of the second MS analysis and the feature quantities corresponding to the first ions to be analyzed in the first MS / MS analysis, thereby enabling the selection of the analytes with higher selectivity, thereby enabling more efficient mass analysis of the sample.

[0172] The embodiments disclosed herein are intended to be combined as appropriate within the scope of any technical inconsistency. The embodiments disclosed herein should be considered to be illustrative and not restrictive in all respects. The scope of the present invention is defined by the claims, not by the description of the above-mentioned embodiments, and is intended to include all modifications within the meaning and scope of the claims.

[0173] 2 Measuring device, 4 Power supply device, 6 Data processing device, 20 Vacuum chamber, 21 ESI source, 22 Desolvation tube, 23, 25, 28 Ion guide, 24 Skimmer, 26 Quadrupole mass filter, 27 Collision cell, 29 Transfer electrode, 30 Orthogonal acceleration electrode, 31 Acceleration electrode, 32 Flight tube, 33 Reflectron, 34 Back plate, 35 Detector, 60 Control unit, 61 Processor, 62 Memory, 63 Input / output I / F, 64 Display, 65 Input device, 100 Mass analyzer, 200 Ionization chamber, 201 First intermediate chamber, 202 Second intermediate chamber, 203 First analysis chamber, 204 Second analysis chamber.

Claims

1. A mass spectrometry method using a mass spectrometer capable of performing MS (mass spectrometry) analysis for performing mass analysis on a group of ions obtained by ionizing a sample, and MS / MS analysis for performing mass analysis on a group of ions obtained by fragmenting selected ions from the group of ions obtained by ionizing a sample, wherein the mass spectrometer is capable of performing MS analysis and MS / MS analysis under each of a first state for detecting a first ion having a first polarity and a second state for detecting a second ion having a second polarity opposite to the first polarity, and the mass spectrometry method includes the steps of: performing a first MS analysis under the first state; performing a first ion selection process for selecting a first ion to be analyzed based on a result of the first MS analysis; performing a first MS / MS analysis under the first state with the first ion selected in the first ion selection process as the analysis target; switching from the first state to the second state; performing a second MS analysis under the second state; and performing a second ion selection process for selecting a second ion to be analyzed based on a result of the second MS analysis. performing a second MS / MS analysis under the second state, with the second ion selected in the second ion selection process as the analysis target, wherein the step of performing the second ion selection process includes a step of performing a first selection process to select the second ion as the analysis target based on a result of the second MS analysis and a first feature amount corresponding to the selected first ion, and the step of performing the second MS / MS analysis includes a step of performing a second MS / MS analysis with the second ion selected in the first selection process as the analysis target.

2. The mass analysis method according to claim 1, wherein the first characteristic amount is a characteristic amount indicative of a second ion that is presumed to have a common pre-ionization component to the pre-ionization component of the selected first ion.

3. A mass analysis method as described in claim 2, wherein the step of performing the first selection process includes a step of selecting, from among the second ions detected in the second MS analysis, a second ion corresponding to the first characteristic amount as the second ion to be analyzed.

4. A mass spectrometry method as described in claim 2 or 3, wherein the step of performing the first selection process includes a step of selecting a second ion to be analyzed from among the second ions detected in the second MS analysis, other than the second ion corresponding to the first characteristic amount.

5. The mass spectrometry method according to claim 2, further comprising the steps of: determining a valence of the selected first ion based on a result of a first MS analysis referred to in the first ion selection process; estimating an exact mass of a specific component before ionization of the selected first ion based on the determined valence and a first ion candidate including at least one of an ion that is added to a component in the sample to generate a first ion and an ion that is desorbed from the component in the sample to generate the first ion; and determining the first feature amount indicating a second ion estimated to be generated by ionizing the specific component based on the estimated exact mass of the specific component and a second ion candidate including at least one of an ion that is added to a component in the sample to generate a second ion and an ion that is desorbed from the component in the sample to generate the second ion.

6. A mass spectrometry method as described in claim 1 or 2, wherein the step of performing the first ion selection process includes a step of selecting a first ion to be analyzed based on at least one of information on the mass-to-charge ratio and detection intensity of the first ion detected in the first MS analysis.

7. The mass spectrometry method according to claim 1 or 2, wherein the step of performing the second ion selection process further includes a second selection process of selecting a second ion to be analyzed based on at least one of information on the mass-to-charge ratio and detection intensity of the second ion detected in the second MS analysis without using the first feature amount, and the step of performing the second MS / MS analysis further includes a step of performing a second MS / MS analysis using the second ion selected in the second selection process as the analysis target.

8. The mass analysis method according to claim 7, wherein the step of performing a second MS / MS analysis using the second ions selected in the first selection process as the analysis target, and the step of performing a second MS / MS analysis using the second ions selected in the second selection process as the analysis target are performed without switching to the first state.

9. The mass spectrometry method according to claim 8, wherein the result of the second MS analysis referred to in the first selection process and the result of the second MS analysis referred to in the second selection process are common.

10. The mass spectrometry method according to claim 8, wherein the step of performing the second MS analysis includes the steps of: performing the second MS analysis after switching from the first state to the second state; and performing the second MS analysis again without switching to the first state after the second MS analysis performed after switching to the second state, wherein the result of the second MS analysis referred to in the first selection process and the result of the second MS analysis referred to in the second selection process are different.

11. A mass spectrometry method as described in claim 1 or 2, wherein the step of performing the first MS analysis includes a step of performing a first MS analysis after switching from the second state to the first state, and the step of performing the first ion selection processing includes a step of selecting a first ion to be analyzed based on a result of the first MS analysis performed after switching to the first state and a second feature corresponding to a second ion selected in the first selection processing.

12. A mass spectrometer capable of performing MS analysis in which mass analysis is performed on a group of ions obtained by ionizing a sample, and MS / MS analysis in which mass analysis is performed on a group of ions obtained by fragmenting selected ions from the group of ions obtained by ionizing a sample, the mass spectrometer comprising: a measurement unit having a mass separation unit that separates ions according to their mass-to-charge ratio; a power supply unit that applies a voltage to the mass separation unit; and a control unit that controls the measurement unit and the power supply unit, and capable of performing MS analysis and MS / MS analysis under each of a first state in which a first ion having a first polarity is detected and a second state in which a second ion having a second polarity opposite to the first polarity is detected, the control unit performing: a step of controlling the measurement unit and the power supply unit to perform a first MS analysis performed under the first state; a step of performing a first ion selection process to select a first ion to be analyzed based on a result of the first MS analysis; and a step of controlling the measurement unit and the power supply unit to perform a first MS / MS analysis performed under the first state with the first ion selected in the first ion selection process as the analysis target.

13. A mass spectrometer comprising: a step of controlling the power supply unit to switch a voltage applied to the mass separation unit, thereby switching from the first state to the second state; a step of controlling the measurement unit and the power supply unit to perform a second MS analysis performed under the second state; a step of performing a second ion selection process to select a second ion to be analyzed based on a result of the second MS analysis; and a step of controlling the measurement unit and the power supply unit to perform a second MS / MS analysis performed under the second state, with the second ion selected in the second ion selection process as the analysis target; wherein the step of performing the second ion selection process includes a step of performing a first selection process to select a second ion to be analyzed based on a result of the second MS analysis and a first feature amount corresponding to the selected first ion; and wherein the step of performing the second MS / MS analysis includes a step of performing a second MS / MS analysis with the second ion selected in the first selection process as the analysis target.

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