Mass analysis method and mass analysis device

Abstract

A mass spectrometry method performs MS scan measurement of a target compound (step 2), selects one or more precursor ion candidates from detected ions on the basis of a first reference related to the measurement intensity (step 5), and performs MS / MS scan measurement using each precursor ion candidate (step 6). A product ion candidate is selected from the detected product ions on the basis of a second reference relating to the measurement intensity (step 9), and the group of precursor ion candidates and product ion candidates is determined as an MRM transition (step 10), in which the group of precursor ion candidates and product ion candidates is selected from the detected product ions on the basis of a second reference relating to the measurement intensity. The mass resolution in the high mass-to-charge ratio or in the high mass-to-charge ratio range is made lower than the mass resolution in the low mass-to-charge ratio or in the low mass-to-charge ratio range so that the measurement sensitivity in the high mass-to-charge ratio or in the high mass-to-charge ratio range becomes higher.

Description

Technical Field

[0001] The present invention relates to a mass analysis method and a mass analysis device. Background Art

[0002] In order to identify or quantify the target compound contained in the sample, an MRM measurement using a mass spectrometer is performed (e.g., Patent Document 1). In the MRM measurement, ions with a predetermined mass-to-charge ratio are screened out from the ions generated by the sample as precursor ions, the precursor ions are cracked to generate product ions, and ions with a predetermined mass-to-charge ratio are screened out from the generated product ions as product ions, and their intensities are measured. The group of precursor ions and product ions used for MRM measurement is called an MRM transition. The target compound is identified based on the measured intensity ratio of multiple MRM transitions. In addition, the target compound is quantified based on the measured intensity of the MRM transition.

[0003] In the case where the MRM measurement conditions including the MRM transition of the target compound are recorded in an existing database, it is possible to perform MRM measurement by reading the MRM measurement conditions from the database. On the other hand, in the case where the MRM measurement conditions of the target compound are not recorded in the database, the analyst needs to decide the MRM transition of the target compound on his own. When deciding the MRM transition, first, an MS scan measurement of the target compound is performed to measure the intensity of the ions generated by the target compound, and one or more ions with a larger measured intensity are selected as precursor ion candidates. Subsequently, an MS / MS scan measurement is performed using each of the one to multiple precursor ion candidates to measure the intensity of the product ions generated from each precursor ion candidate. Then, one or more product ion candidates with a larger measured intensity are selected for each precursor ion candidate, and the combination of the precursor ion candidate and the product ion candidate is determined as the MRM transition.

[0004] Prior art literature

[0005] Patent Literature

[0006] Patent Document 1: International Publication No. 2017 / 046867

[0007] Patent Document 2: International Publication No. 2009 / 141852 Summary of the Invention

[0008] Technical problem to be solved by the invention

[0009] In a mass spectrometer, the measurement intensity of ions with a large mass-to-charge ratio (e.g., a mass-to-charge ratio of 1000 or more) is often reduced compared to ions with a small mass-to-charge ratio (e.g., a mass-to-charge ratio of 800 or less). There are several main reasons for this. For example, as one main reason, the ion transport optical system that transports ions in the mass spectrometer is designed to have a high transport efficiency for ions with a low mass-to-charge ratio. In addition, as other main reasons, for example, the conversion dynode used as a detector in the mass spectrometer emits a number of electrons corresponding to the flight speed of the ions. Therefore, the number of electrons generated when ions with a high mass-to-charge ratio and a small flight speed are incident on the conversion dynode is less than the number of electrons generated when ions with a low mass-to-charge ratio and a large flight speed are incident on the conversion dynode. Therefore, the measurement intensity of ions with a small mass-to-charge ratio becomes larger, and precursor ions and product ions with a small mass-to-charge ratio are easily determined as MRM transitions.

[0010] Compounds with similar structures and properties will generate precursor ions with similar mass-to-charge ratios, or generate the same product ions. For example, when the target compound is a peptide, b-series ions are easily generated. In addition, when the target compound is a nucleic acid, a large number of ions derived from phosphate groups are generated. Therefore, when the target compound is a peptide or nucleic acid, these ions with a small mass-to-charge ratio are easily selected when determining the MRM transition. However, b-series ions with a small mass-to-charge ratio are generated by multiple different peptides, and ions derived from phosphate groups with a small mass-to-charge ratio may be generated by multiple different nucleic acids. In this way, ions with a small mass-to-charge ratio are smaller than ions with a large mass-to-charge ratio, so in most cases the target compound does not have a characteristic structure. Therefore, if such ions are used for MRM transition, the compound selectivity of the MRM transition becomes low, and there is a possibility that mixed compounds with similar structures and properties will be mistakenly measured as target compounds.

[0011] While the analysis of target compounds using MRM has been described here, similar issues also arise when analyzing target compounds using SIM measurements of ions with specific mass-to-charge ratios generated by the target compound. In particular, SIM measurements screen compounds in only one stage. Therefore, if the target ions used have low compound selectivity, there is a high risk of mistaking contaminants with similar structures and properties for the target compound for measurement.

[0012] The technical problem to be solved by the present invention is to provide a technology that can accurately analyze target compounds.

[0013] Solutions for solving the above technical problems

[0014] One aspect of the mass spectrometry method of the present invention completed in order to solve the above-mentioned technical problems is:

[0015] A mass spectrometry method comprises performing MS scan measurement of a target compound, selecting one or more precursor ion candidates from ions detected by the MS scan measurement based on a predetermined first criterion related to the measurement intensity,

[0016] performing MS / MS scan measurement using each of the one or more precursor ion candidates, and selecting product ion candidates from product ions detected by the MS / MS scan measurement based on a predetermined second criterion related to the measurement intensity;

[0017] The group of the precursor ion candidate and the product ion candidate is determined as an MRM transition, wherein,

[0018] In the MS scan measurement and / or the MS / MS scan measurement, the mass resolution at a larger mass-to-charge ratio or mass-to-charge ratio range is made lower than the mass resolution at a smaller mass-to-charge ratio or mass-to-charge ratio range in such a manner that the measurement sensitivity at the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

[0019] Another solution of the mass spectrometry method of the present invention completed in order to solve the above-mentioned technical problems is:

[0020] A mass analysis method comprises performing MS scan measurement of a target compound and selecting one or more target ion candidates from ions detected by the MS scan measurement based on a predetermined criterion related to the measurement intensity, wherein:

[0021] In the MS scan measurement, the mass resolution at a larger mass-to-charge ratio or within a mass-to-charge ratio range is made lower than that at a smaller mass-to-charge ratio or within a mass-to-charge ratio range so that the measurement sensitivity within the larger mass-to-charge ratio or within the mass-to-charge ratio range becomes higher.

[0022] Furthermore, one aspect of the mass spectrometer of the present invention, which has been developed to solve the above-mentioned technical problems, comprises:

[0023] a precursor ion candidate determination unit that performs MS scan measurement of a target compound and selects one or more precursor ion candidates from ions detected by the MS scan measurement based on a predetermined first criterion related to measurement intensity;

[0024] a product ion candidate determining unit that performs MS / MS scan measurement using each of the one or more precursor ion candidates and selects a product ion candidate from product ions detected by the MS / MS scan measurement based on a predetermined second criterion related to the measurement intensity;

[0025] an MRM transition determining unit that determines a set of the precursor ion candidate and the product ion candidate as an MRM transition;

[0026] The mass resolution setting unit makes the mass resolution in a larger mass-to-charge ratio or mass-to-charge ratio range lower than the mass resolution in a smaller mass-to-charge ratio or mass-to-charge ratio range in the MS scan measurement and / or the MS / MS scan measurement in such a manner that the measurement sensitivity in the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

[0027] Another aspect of the mass spectrometer of the present invention, which has been developed to solve the above-mentioned technical problems, comprises:

[0028] a target ion determination unit that performs MS scan measurement of a target compound and determines one or more target ions from ions detected by the MS scan measurement based on a predetermined criterion related to the measurement intensity;

[0029] The mass resolution setting unit makes the mass resolution at a larger mass-to-charge ratio or mass-to-charge ratio range lower than the mass resolution at a smaller mass-to-charge ratio or mass-to-charge ratio range in the MS scan measurement so that the measurement sensitivity at the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

[0030] Effects of the Invention

[0031] In the present invention, when performing MS scanning measurement and / or MS / MS scanning measurement, the mass resolution within a larger mass-to-charge ratio or mass-to-charge ratio range is made lower than the mass resolution within a smaller mass-to-charge ratio or mass-to-charge ratio range to improve the measurement sensitivity within the larger mass-to-charge ratio or mass-to-charge ratio range. Although there are various methods to reduce mass resolution, in the present invention, the mass resolution is not simply reduced, but is reduced by a method associated with improving measurement sensitivity. Therefore, compared with the past, it is easier to select ions with a large mass-to-charge ratio as MRM transitions or target ions. Compared with ions with a small mass-to-charge ratio, ions with a large mass-to-charge ratio are larger in themselves and, in most cases, have characteristic structures in the target compound. In the present invention, since ions with characteristic structures and high compound selectivity in the target compound are determined as MRM transitions or target ions, even when measuring a sample containing the target compound and an impurity compound with similar structures and characteristics, only the target compound can be measured. Therefore, the target compound can be accurately analyzed. BRIEF DESCRIPTION OF THE DRAWINGS

[0032] Figure 1 This is a diagram showing the main structure of a mass spectrometer according to an embodiment of the present invention.

[0033] Figure 2 This is a flowchart of one embodiment of the mass spectrometry method of the present invention for determining MRM transition using the mass spectrometer of this embodiment.

[0034] Figure 3This is a comparison between the MS spectrum obtained by conventional MS scan measurement and the MS spectrum obtained by MS scan measurement in this embodiment.

[0035] Figure 4 This is a comparison between the MS spectrum obtained by conventional MS / MS scan measurement and the MS spectrum obtained by MS / MS scan measurement in this embodiment.

[0036] Figure 5 This is an MS / MS spectrum illustrating an example in which identical or similar ions are not selected when selecting product ion candidates.

[0037] Figure 6 This is a flowchart of another embodiment of a mass analysis method for determining target ions in SIM measurement. DETAILED DESCRIPTION

[0038] Hereinafter, embodiments of a mass spectrometry method and a mass spectrometry apparatus according to the present invention will be described with reference to the accompanying drawings.

[0039] Figure 1 1 is a diagram showing the main configuration of a mass spectrometer 1 according to the present embodiment. The mass spectrometer according to the present embodiment includes a mass spectrometer unit 10 and a control and processing unit 40 .

[0040] The mass spectrometer 10 includes an ionization chamber 11 and a vacuum chamber. The vacuum chamber is evacuated by a vacuum pump (not shown). Inside the vacuum chamber, a first intermediate vacuum chamber 12, a second intermediate vacuum chamber 13, and an analysis chamber 14 are arranged in this order, starting from the ionization chamber 11. The vacuum level is increased in this order, using a multi-stage differential exhaust system.

[0041] The ionization chamber 11 is equipped with an electrospray ionization (ESI) probe 111, which imparts an electric charge to the sample solution and sprays it. Liquid samples can be introduced directly into the ESI probe 111, or sample components separated by the liquid chromatograph's columns can be introduced by connecting a liquid chromatograph upstream. The ionization chamber 11 communicates with the subsequent first intermediate vacuum chamber 12 via a thin heated capillary 112.

[0042] An ion guide 121 composed of a plurality of rod electrodes is disposed in the first intermediate vacuum chamber 12. The ion guide 121 converges the ion flight path along the central axis of the ion flight path, namely, the ion optical axis C. The first intermediate vacuum chamber 12 and the second intermediate vacuum chamber 13 are separated by a skive 122 having a small hole at the top.

[0043] An ion guide 131 composed of a plurality of rod electrodes is disposed in the second intermediate vacuum chamber 13. Like the ion guide 121, the ion guide 131 converges the flight path of ions along the ion optical axis C. The second intermediate vacuum chamber 13 and the analysis chamber 14 are separated by a partition wall having a small hole.

[0044] The analysis chamber 14 is equipped with a front-stage quadrupole mass filter 15, a collision cell 16, a rear-stage quadrupole mass filter 17, and an ion detector 18. The front-stage quadrupole mass filter 15 includes a front rod electrode 151, a main rod electrode 152, and a rear rod electrode 153. A multipole ion guide 161 is arranged within the collision cell 16. Collision-induced dissociation (CID) gas is introduced into the collision cell 16 from a gas source (not shown). The rear-stage quadrupole mass filter 17 includes a front rod electrode 171 and a main rod electrode 172.

[0045] The mass spectrometer 10 can perform MS scan measurement, selected ion monitoring (SIM) measurement, MS / MS scan (product ion scan) measurement, and multiple reaction monitoring (MRM) measurement. In MS scan measurement, the mass-to-charge ratio of ions passing through the post-stage quadrupole mass filter 17 is scanned. In SIM measurement, the mass-to-charge ratio of ions passing through the post-stage quadrupole mass filter 17 is fixed, allowing only product ions with a specific mass-to-charge ratio to pass through and be detected by the ion detector 18.

[0046] In MS / MS scanning and MRM measurements, both the front-stage quadrupole mass filter 15 and the rear-stage quadrupole mass filter 17 function as mass filters. Only ions designated as precursor ions are allowed to pass through the front-stage quadrupole mass filter 15. CID gas is supplied to the interior of the collision cell 16, and the precursor ions are accelerated by imparting energy (collision energy) and introduced into the collision cell. The precursor ions collide with the CID gas, causing the precursor ions to fragment. In MS / MS scanning, the mass-to-charge ratio of ions passing through the rear-stage quadrupole mass filter 17 is scanned. In MRM, the mass-to-charge ratio of ions passing through the rear-stage quadrupole mass filter 17 is fixed, allowing only product ions with a specific mass-to-charge ratio to pass through and be detected by the ion detector 18.

[0047] The control and processing unit 40 includes a storage unit 41. The storage unit 41 stores a compound database in which information such as measurement conditions and analysis methods related to a plurality of known compounds is recorded.

[0048] The control and processing unit 40 includes a measurement condition setting unit 42, a measurement execution unit 43, a precursor ion candidate determination unit 44, a product ion candidate determination unit 45, an MRM transition determination unit 46, and a target ion determination unit 47 as functional blocks. The measurement condition setting unit 42 includes a mass resolution setting unit 421 and a weighting setting unit 422. The control and processing unit 40 is implemented as a personal computer, and the aforementioned components function by executing a dedicated program pre-installed on the computer via a processor. Furthermore, the control and processing unit 40 is connected to an input unit 5 comprising a mouse, keyboard, etc., and a display unit 6 comprising a liquid crystal display, etc.

[0049] The mass spectrometer 1 of the present embodiment can be used to analyze (identify, quantify) the target compound by performing SIM measurement or MRM measurement on the target compound contained in the sample. In the case where the conditions for the SIM measurement or MRM measurement of the target compound are recorded in the compound database stored in the storage unit 41, the information is read out to perform the analysis of the target compound. On the other hand, in the case where the measurement conditions of the target compound are not recorded in the compound database, first, it is necessary to determine the measurement conditions of the target compound. The mass spectrometer 1 and the mass analysis method of the present embodiment are characterized in that the processing of determining the conditions for the SIM measurement and MRM measurement of the target compound is performed.

[0050] Figure 2 This is a flow chart of one embodiment of the mass spectrometry method of the present invention. In the mass spectrometry method of this embodiment, the MRM measurement conditions of the target compound are determined.

[0051] When the user performs a predetermined input operation, the measurement condition setting unit 42 allows the user to input the name of the target compound. Furthermore, when determining the MRM measurement conditions, the display unit 6 displays a screen for selecting whether to change the mass resolution from that used in normal measurement and whether to weight ions in the high mass-to-charge ratio range.

[0052] When the user selects to change the mass resolution, the mass resolution setting unit 421 allows the user to input the mass-to-charge ratio range for the changed mass resolution and the changed mass resolution. Many mass spectrometers control the applied voltage values ​​and operation of various components to increase the mass resolution during mass analysis. For example, the output signal from the ion detector 18 is processed so that the half-value width of the peak in the mass spectrum is 0.7. Hereinafter, this mass resolution setting is referred to as "Unit."

[0053] Typically, in a mass spectrometer, the measurement sensitivity of ions with a large mass-to-charge ratio (e.g., a mass-to-charge ratio of 1000 or more) is often reduced by about one digit compared to ions with a small mass-to-charge ratio (e.g., a mass-to-charge ratio of 800 or less). There are several main reasons for this. For example, as one main reason, the plasma transport optical system, such as the ion guides 121 and 131, that transport ions in the mass spectrometer is designed to have a high transport efficiency for ions with a low mass-to-charge ratio. In addition, as another main reason, the conversion dynode, which is widely used as an ion detector, emits a number of electrons corresponding to the flight speed of the ions. Therefore, the number of electrons generated when ions with a low mass-to-charge ratio and a low flight speed enter the conversion dynode is smaller than the number of electrons generated when ions with a low mass-to-charge ratio and a high flight speed enter the conversion dynode.

[0054] In this embodiment, taking the above-mentioned aspects into consideration, the measurement conditions are determined so that the measurement intensity in the high mass-to-charge ratio range is equal to or greater than the measurement intensity in the low mass-to-charge ratio range. Here, the mass resolution in the low mass-to-charge ratio range (the range where m / z is less than 1000) is set to the aforementioned Unit, and in the high mass-to-charge ratio range (the range where m / z is 1000 or greater), the mass resolution is set so that the output signal from the ion detector 18 is processed so that the half-width of the peak in the mass spectrum is 3.0. Hereinafter, the latter mass resolution setting will be referred to as "Low."

[0055] When the user chooses to give weight to the high mass-to-charge ratio range, the weight setting unit 422 allows the user to input the mass-to-charge ratio range and weighting content to be set next. Typically, the weighted mass-to-charge ratio range is set to be the same as the mass range that reduces the mass resolution and increases the measurement sensitivity, but it can also be set to a different mass-to-charge ratio range. The weighting content can be set, for example, to multiply the measured intensity by a coefficient that is a constant, or multiply by a coefficient calculated by taking the value of the mass-to-charge ratio as a function of a variable. The following describes a case where a constant coefficient k (k>1. For example, k=2) is set to be multiplied by the measured intensity.

[0056] Once the mass resolution and weighting settings are complete, the measurement condition setting unit 42 allows the user to enter the mass scan range for MS scan measurements, the mass scan range for MS / MS scan measurements, and the collision energy (CE) value. CE represents the amount of energy imparted to the precursor ions during their dissociation. Here, as an example, 11 measurement conditions are set, varying in 5V increments within the range of 5V to 50V. Furthermore, the mass scan range for both MS scan measurements and MS / MS scan measurements is set to 0 to 2000.

[0057] The user sets the aforementioned measurement conditions (step 1). When the user instructs the start of measurement, the measurement execution unit 43 prompts the user to introduce a liquid sample containing a predetermined amount of the target compound into the ESI probe 111. Once the user introduces the liquid sample into the ESI probe 111, the measurement execution unit 43 performs an MS scan measurement within the mass scan range set as the aforementioned measurement conditions (step 2). Detection signals of ions incident on the ion detector 18 during the measurement are sequentially transmitted to the control and processing unit 40 and stored in the storage unit 41.

[0058] When the MS scan measurement is completed, the measurement execution unit 43 reads the output signal from the ion detector 18 stored in the storage unit 41. Then, a mass window of Unit, i.e., a mass peak half-width of 0.7, is set for the detection intensity in the mass-to-charge ratio range of less than 1000 (low mass-to-charge ratio range). A mass window of Low, i.e., a mass peak half-width of 3.0, is set for the detection signal in the mass-to-charge ratio range of 1000 or more (high mass-to-charge ratio range). The detection signals within the range of each mass window are added.

[0059] Reference Figure 3 The effects of performing the above-mentioned processing will be described. Figure 3 : is an example of an MS spectrum obtained by MS scanning measurement. The upper part is an MS spectrum obtained when the mass window of Unit is set in the entire mass scanning range (comparative example), and the lower part is an MS spectrum produced by setting the mass window of Unit in the low mass-to-charge ratio range and the mass window of Low in the high mass-to-charge ratio range as in this embodiment (exemplary example). In addition, Figure 3 The MS spectra at the upper and lower parts of are obtained by extracting the portion with a mass-to-charge ratio of 500 to 1300 in the mass scan range.

[0060] In the Unit mass window, the isotope ions are separated and the measured intensities are calculated for each. On the other hand, in the Low mass window, the detection intensities of isotope ions with a mass-to-charge ratio difference of about 1 are added together. For example, Figure 3 In the upper MS spectrum (Unit), the mass peak of the isotope ion appears adjacent to the mass peak of the ion with a mass-to-charge ratio of 1203, but in the lower MS spectrum (Low), these peaks become a single mass peak. Focusing on the mass peak of the ion with a mass-to-charge ratio of 603 and the mass peak of the ion with a mass-to-charge ratio of 1203, it can be seen that the peak intensity of the former is approximately 150,000 in both the upper and lower MS spectra. In contrast, the peak intensity of the latter increases from approximately 430,000 in the upper MS spectrum to approximately 1,400,000, an increase of approximately 3.3 times.

[0061] The precursor ion candidate determination unit 44 extracts the MS spectrum ( Figure 3The mass peak that occurs in the MS spectrum at the bottom is selected to make a peak list that associates this mass-to-charge ratio with the measurement intensity. In addition, for the measurement intensity of the mass peak in the high mass-to-charge ratio range, after multiplying by the weighting coefficient k set in advance by the user (step 3), each mass peak is arranged in the order of measurement intensity (step 4). Then, in the high mass-to-charge ratio range and the low mass-to-charge ratio range, the mass peaks of a predetermined quantity (for example, the high mass-to-charge ratio range is 2, and the low mass-to-charge ratio range is 1) are extracted separately from the order of measurement intensity from high to low, and the ion of the mass-to-charge ratio corresponding to the mass peak is selected as a precursor ion candidate (step 5). By extracting the mass peak like this, it is possible to extract at least the mass peak of the above-mentioned predetermined quantity from the high mass-to-charge ratio range and select the precursor ion candidate. Alternatively, in step 5, it is also possible to extract the mass peak of a predetermined quantity (for example, 3) from the order of the measurement intensity after assigning weighting from high to low within the whole mass-to-charge ratio range, select the precursor ion candidate.

[0062] However, even if the mass peak has a high measured intensity, it will be excluded if the difference in mass-to-charge ratio between it and the mass peak of the ion that has been selected as the precursor ion candidate is less than a predetermined value. Specifically, for example, for ions with a mass-to-charge ratio within a range of ±5 centered on the mass-to-charge ratio of the ion that has been selected as the precursor ion candidate, they will not be selected as precursor ion candidates even if the mass peak has a high measured intensity. This can prevent multiple isotope ions with substantially the same structure from being selected as precursor ion candidates. Here, a predetermined number of mass peaks are extracted in descending order of measured intensity, but it is also possible to extract all mass peaks with measured intensities exceeding a predetermined threshold, or to extract a specified number of mass peaks with measured intensities exceeding a predetermined threshold in descending order of mass-to-charge ratio.

[0063] In step 5, the larger the weighting coefficient k is, the easier it is to select ions in the high mass-to-charge ratio range as precursor ion candidates. Therefore, the weighting coefficient k can be set in advance according to the degree to which ions with high mass-to-charge ratio are valued as precursor ion candidates. Alternatively, the user can set or change the weighting coefficient k after confirming the mass spectrum obtained by measurement. In the present embodiment, the weighting coefficient k is set, but as mentioned above, the measurement sensitivity of ions with high mass-to-charge ratio has been improved by reducing the mass-to-charge ratio. Therefore, when setting the measurement conditions, no weighting is required if the measurement intensity does not need to be further increased. In addition, ions generated by compounds (solvents, mobile phases, etc.) other than the target compound contained in the liquid sample can also be set as excluded ions in advance. In step 5, ions that are the same as the excluded ions or whose mass-to-charge ratio is close to that of the excluded ions are excluded from the selection object. The same is also true in the MS / MS scanning measurement described later.

[0064] After a precursor ion candidate is selected in step 5, the measurement execution unit 43 performs an MS / MS scan measurement on each of the three precursor ion candidates under the previously set measurement conditions (11 measurement conditions with different CE values) (step 6). When the user introduces a liquid sample into the ESI probe 111, the measurement execution unit 43 performs an MS / MS scan measurement on each of the three precursor ion candidates under the 11 different measurement conditions, i.e., sequentially performs 33 MS / MS scan measurements (step 6). Detection signals of ions incident on the ion detector 18 during the measurement are sequentially transmitted to the control and processing unit 40 and stored in the storage unit 41.

[0065] When the MS / MS scan measurement is completed, the measurement execution unit 43 reads the output signal from the ion detector 18 stored in the storage unit 41. Then, a mass window of Unit, i.e., a mass peak half-width of 0.7, is set for the detection intensity in the mass-to-charge ratio range of less than 1000 (low mass-to-charge ratio range). A mass window of Low, i.e., a mass peak half-width of 3.0, is set for the detection signal in the mass-to-charge ratio range of 1000 or more (high mass-to-charge ratio range). The detection signals within the ranges of these mass windows are then summed.

[0066] Figure 4 Examples of MS / MS spectra (product ion spectra) obtained by MS / MS scanning measurements are shown. The upper portion is an MS spectrum obtained when the mass window of Unit is set over the entire mass scan range (comparative example), and the lower portion is an MS spectrum produced by setting the mass window of Unit in the low mass-to-charge ratio range and the mass window of Low in the high mass-to-charge ratio range as in this embodiment (exemplary example). In addition, Figure 4 The MS spectra at the upper and lower parts of are obtained by extracting the portion with a mass-to-charge ratio of 0 to 1200 in the mass scan range.

[0067] If also Figure 3 As explained in the MS spectra of , in the Unit mass window, isotope ions are separated and their respective measured intensities are calculated. Meanwhile, in the Low mass window, the detected intensities of isotope ions with mass-to-charge ratios differing by approximately 1 are summed. Focusing on the mass peak of the ion with a mass-to-charge ratio of 637 and the mass peak of the ion with a mass-to-charge ratio of 1185 (1184 in the lower part), it can be seen that the peak intensity of the former is approximately 28,000 in both the upper and lower MS spectra. In contrast, the peak intensity of the latter increases from approximately 110,000 in the upper MS spectrum to approximately 410,000, a 3.7-fold increase.

[0068] The product ion candidate determination unit 45 extracts 33 MS / MS spectra (MS / MS spectra acquired for each of the three precursor ion candidates under 11 different measurement conditions) prepared by the measurement execution unit 43. One example is Figure 4The mass peak that appears in each of the MS spectra (the MS spectrum at the bottom) is used to make a peak list that associates the mass-to-charge ratio with the measurement intensity. In addition, for the measurement intensity of the mass peak in the high mass-to-charge ratio range, after multiplying it by the weighting coefficient k set in advance by the user (step 7), the mass peaks are arranged in the order of the measurement intensity (step 8). Then, in the high mass-to-charge ratio range and the low mass-to-charge ratio range, a predetermined number (for example, 3 for the high mass-to-charge ratio range and 2 for the low mass-to-charge ratio range) of mass peaks are extracted separately in the order of the measurement intensity from high to low, and ions with mass-to-charge ratios corresponding to the mass peaks are selected as product ion candidates (step 9). By extracting the mass peaks in this way, it is possible to extract at least the above-mentioned predetermined number of mass peaks from the high mass-to-charge ratio range and select product ion candidates. Alternatively, in step 9, it is also possible to extract a predetermined number (for example, 3) of mass peaks in the order of the weighted measurement intensity from high to low within the entire mass-to-charge ratio range to select product ion candidates.

[0069] exist Figure 5 2 shows an example in which ions with similar mass-to-charge ratios are not selected as precursor ion candidates or product ion candidates in steps 5 and 9. Figure 5 This is an example of a product ion spectrum obtained by MS / MS scanning measurement.

[0070] Figure 5 This is a graph obtained by extracting the mass-to-charge ratio range of 215 to 440 from the product ion spectrum. High-intensity mass peaks appear at positions with mass-to-charge ratios of 224, 241, 255, 298, 388, 397, 425, and 439. When these mass peaks are used as product ion candidates, ions whose mass-to-charge ratios differ from those of the ions are excluded from the product ion candidate list. For example, for the mass peak with a mass-to-charge ratio of 298, ions with mass-to-charge ratios within the range surrounded by the dotted line are excluded. As a result, although the mass peaks appearing on the low mass-to-charge ratio side of the mass peak with a mass-to-charge ratio of 298 have higher intensities, they are excluded from the product ion candidate list. Mass peaks appearing near the high-intensity mass peaks are mostly peaks of isotopic ions. Even if such an isotope ion mass peak is selected as a product ion candidate, it only has the same compound selectivity as the product ion candidate with a mass-to-charge ratio of 298 that has been selected. Therefore, by excluding such isotope ions, the compound selectivity of the final MRM transition can be improved. Figure 5 This is an example of selecting product ion candidates, but the same applies to selecting precursor ion candidates.

[0071] When determining the MRM transition, it is necessary to perform MS / MS scan measurement under measurement conditions in which a plurality of different CE values ​​are associated with each of a plurality of precursor ion candidates selected based on the result of the MS scan measurement. In the case of the present embodiment, the MS / MS scan measurement is performed using each of 33 different measurement conditions. When the mass scan range is wide or the CE value is set finely, the time required for a series of measurements becomes further longer. In order to perform such measurements within a limited time, it is necessary to increase the mass scan speed in the MS / MS scan measurement. However, if the mass scan speed is increased, the MS / MS spectrum sometimes produces mass deviation. As a result, in different MS / MS scan measurements, the same product ion is sometimes measured as an ion with a slightly different mass-to-charge ratio (e.g., ±1 different). For example, when product ions with a mass-to-charge ratio of 99, 100, and 101 are measured at high intensity and all of these three product ions are selected, the final decision includes three MRM transitions of the same product ion. However, the compound selectivity of these three ions is the same, and even if an MRM transition containing these three product ions is used, there is no effect of improving compound selectivity. In this embodiment, selection of a plurality of identical product ions can also be avoided by excluding ions whose mass-to-charge ratios are within a predetermined range centered around the mass-to-charge ratio of the ion already selected as the product ion candidate.

[0072] When product ion candidates are selected in step 9 , the MRM transition determination unit 46 determines the result of associating each product ion candidate with the precursor ion candidate that generated the product ion candidate as an MRM transition (step 10 ).

[0073] When an MRM transition is determined for a target compound, the measurement execution unit 43 confirms whether an MRM transition has been determined for all target compounds. If there is a target compound for which an MRM transition has not yet been determined (no in step 11), the same steps are performed for the next target compound to determine an MRM transition. The measurement conditions for the target compounds set in step 1 can be common to all compounds or different for each compound.

[0074] When the MRM transition is determined for all target compounds (yes in step 11), the MRM transition determination unit 46 refers to the mass-to-charge ratios of the precursor ions and product ions contained in the MRM transitions determined for each compound to determine whether there are target compounds whose values ​​are close to each other (for example, the difference in mass-to-charge ratio is within ±5). In the case of a target compound with a close mass-to-charge ratio that determines an MRM transition of the precursor ion and / or product ion, the MRM transition is annotated (step 13). Specifically, it is annotated as "the mass-to-charge ratio of the precursor ion or product ion is similar to that of compound A (compound name)". Thus, when the user analyzes a sample that may contain both the target compound and other compounds, it is possible to avoid misidentification or errors in quantitative values ​​due to the use of MRM transitions with lower selectivity for these compounds. After the above series of steps, the MRM transition determination unit 46 saves the MRM transitions determined for each target compound in the compound database of the storage unit 41 (step 14). If the answer is "No" in step 12, the MRM transition determined in step 11 is stored directly in the compound database (step 14).

[0075] In the above, MRM transitions for precursor ions or product ions with similar mass-to-charge ratios between the MRM transitions determined in this measurement were extracted. However, it is also possible to further confirm whether there are MRM transitions with similar mass-to-charge ratios (for example, the difference in mass-to-charge ratio is within ±5) to those of the MRM transitions of each compound recorded in the compound database and annotate them. In this case, the MRM transitions already stored in the compound database can be annotated in the same way.

[0076] As described above, in a mass spectrometer, the measured intensity of ions with a large mass-to-charge ratio (e.g., a mass-to-charge ratio of 1000 or greater) is often lower than that of ions with a small mass-to-charge ratio (e.g., a mass-to-charge ratio of 800 or less). Therefore, when MS scan measurements or MS / MS scan measurements are performed with the same mass resolution across the entire mass scan range, the measured intensity of ions with a small mass-to-charge ratio increases, making precursor ions and product ions with small mass-to-charge ratios more likely to be determined as MRM transitions.

[0077] Compounds with similar structures and properties will generate precursor ions with similar mass-to-charge ratios, or produce identical product ions. For example, when the target compound is a peptide, b-series ions are easily generated. In addition, when the target compound is a nucleic acid, a large number of ions derived from phosphate groups are generated. Therefore, when the target compound is a peptide or nucleic acid, these ions with small mass-to-charge ratios are easily selected when determining the MRM transition. However, b-series ions with small mass-to-charge ratios are generated by multiple different peptides, and ions derived from phosphate groups with small mass-to-charge ratios may be generated by multiple different nucleic acids. In this way, ions with small mass-to-charge ratios are smaller than ions with large mass-to-charge ratios, so in most cases the target compound does not have a characteristic structure. Therefore, if such ions are used for MRM transitions, the compound selectivity of the MRM transition becomes low, and there is a possibility that mixed compounds with similar structures and properties will be mistakenly measured as target compounds. In addition, in the low mass-to-charge ratio range, ions derived from the mobile phase are easily detected, or noise from the equipment is easily superimposed. Therefore, there is a problem of difficulty in accurately analyzing the target compound.

[0078] In contrast, in this embodiment, the measurement sensitivity in the high mass-to-charge ratio range is improved by making the mass window in the high mass-to-charge ratio range larger than the mass window in the low mass-to-charge ratio range. Therefore, it is easier to select ions with a large mass-to-charge ratio as MRM transitions than in the past. Compared with ions with a small mass-to-charge ratio, ions with a large mass-to-charge ratio are larger in themselves and, in most cases, have characteristic structures in the target compound. In this embodiment, since ions with characteristic structures in the target compound and high compound selectivity are determined as MRM transitions, even when measuring a sample containing the target compound and mixed compounds with similar structures and characteristics, it is possible to measure only the target compound.

[0079] Furthermore, by selecting ions with a high mass-to-charge ratio as MRM transitions, the influence of ions and noise originating from the mobile phase during MRM or SIM measurements is reduced, enabling more accurate analysis of target compounds than ever before.

[0080] Furthermore, in the low mass-to-charge ratio range, ions originating from the mobile phase are easily detected, or they are easily superimposed by noise from the equipment. In contrast, in the high mass-to-charge ratio range, noise is intermittent and its intensity is also low. Therefore, by setting the mass window to Low (widening the mass window) in the high mass-to-charge ratio range, the S / N ratio can be improved, resulting in a high-quality mass spectrum.

[0081] While the above description uses an example of determining an MRM transition, similar steps can also be used to determine a target ion in a SIM measurement. In this case, a target ion determination unit 47 is used as a functional block instead of the precursor ion candidate determination unit 44 and the product ion candidate determination unit 45.

[0082] Figure 6 This is a flowchart for determining the target ions in SIM measurement. Figure 2 As can be seen from the comparison, by executing steps 21 to 25, which correspond to steps 1 to 5 executed when determining the MRM transition, the target ion in the SIM measurement can be determined. Furthermore, when determining the target ion, similarly to the above, after the target ions for all target compounds have been determined (yes in step 26), if there are target ions with similar mass-to-charge ratios between different target compounds (yes in step 27), the target ions are annotated (step 28) and stored in the compound database (step 29).

[0083] The above-described embodiment is merely an example and can be modified as appropriate according to the spirit of the present invention.

[0084] In the above embodiment, the measurement sensitivity in the high mass-to-charge ratio range is improved by making the mass window in the high mass-to-charge ratio range larger than the mass window in the low mass-to-charge ratio range. However, as long as the method can improve the measurement sensitivity in the high mass-to-charge ratio range, a method different from the above embodiment can also be used.

[0085] For example, in a mass spectrometer that uses a quadrupole mass filter to mass separate ions, as in the above-described embodiment, a DC voltage and a high-frequency voltage tuned to improve mass resolution are typically applied to each rod electrode. For example, as described in Patent Document 2, a stability region diagram is known as a solution to the Mathieu equation that describes the behavior of ions in a quadrupole electric field. The closer the points corresponding to the DC voltage and high-frequency voltage applied to each rod electrode are to the periphery of the roughly triangular shape represented as the stability region in the stability region diagram, the higher the mass resolution achieved. Applying a DC voltage and high-frequency voltage corresponding to a point located inward of the periphery of the stability region reduces the mass separation capability of the quadrupole mass filter, lowering the mass resolution. However, the ion transmittance increases, leading to higher measurement sensitivity. Therefore, instead of processing the detection signal in the above-described embodiment, applying a DC voltage and high-frequency voltage to each rod electrode corresponding to a point located inward of the points corresponding to the DC voltage and high-frequency voltage typically used in a quadrupole mass filter within the stability region can similarly improve measurement sensitivity for ions in the high mass-to-charge ratio range.

[0086] In the above embodiment, two mass-to-charge ratio ranges are set, namely a low mass-to-charge ratio range with a mass-to-charge ratio less than 1000 and a high mass-to-charge ratio range with a mass-to-charge ratio greater than 1000, but the boundary between the low mass-to-charge ratio range and the high mass-to-charge ratio range can be appropriately changed. If the characteristics of the mass spectrometer described in the above embodiment are taken into consideration, the boundary is preferably set to a value between 800 and 1000. In addition, in the above embodiment, two ranges, namely a low mass-to-charge ratio range and a high mass-to-charge ratio range, are set, and the mass resolution is reduced and the measurement sensitivity is improved for the latter, and a weighting is given to the measurement intensity, but more than three mass-to-charge ratio ranges (for example, three ranges with a mass-to-charge ratio less than 1000, 1000 and less than 1500, and 1500) can be set, and different mass resolutions and weightings are set for the multiple mass-to-charge ratio ranges located on the high mass-to-charge ratio side.

[0087] In the above embodiment, the mass resolution and weighting are set for each mass-to-charge ratio range. However, the mass resolution and weighting can also be set for each mass-to-charge ratio. For example, by setting the width of the mass window used to reduce the mass resolution and / or the weighting coefficient as a function of the mass-to-charge ratio, the mass resolution and weighting values ​​can be continuously changed.

[0088] In the above embodiment, the mass resolution and weighting settings for both the MS scan measurement and the MS / MS scan measurement used to determine the MRM measurement conditions are the same, but the settings for each of the MS scan measurement and the MS / MS scan measurement may be different. Furthermore, in the above embodiment, the mass resolution in the high mass-to-charge ratio range is reduced to increase measurement sensitivity and weighting is set in both the MS scan measurement and the MS / MS scan measurement used to determine the MRM measurement conditions. However, the mass resolution in the high mass-to-charge ratio range may be changed or weighting may be set for only one of the MS scan measurement and the MS / MS scan measurement.

[0089] In the above embodiment, by setting the measurement conditions related to the processing of the measurement signal obtained from the ion detector 18 in the low mass-to-charge ratio range and the high mass-to-charge ratio range to Unit and Low, the mass resolution is reduced in the high mass-to-charge ratio range and the measurement sensitivity is improved, but the mass resolution can also be reduced by using other measurement conditions to improve the measurement sensitivity.

[0090] In the above embodiment, when selecting precursor ion candidates and product ion candidates, ions whose mass-to-charge ratio differs from that of already selected ions by less than ±5 are not selected. However, this value can be appropriately changed (e.g., within a range of ±1 to 10) depending on the characteristics of the target compound. For example, when the target compound is a peptide, by setting this value to approximately ±100 to 150 (e.g., ±120), i.e., a value corresponding to the mass number of one base, it is possible to avoid selecting multiple ions with the same number of bases as precursor ion candidates or product ion candidates.

[0091] In the above embodiment, a triple quadrupole mass spectrometer is described in which an ESI probe for ionizing a liquid sample is used as an ion source and a quadrupole mass filter is provided in front and behind the collision cell. However, the ion source may be an ion source corresponding to the characteristics of the sample, and the mass separation unit may also use various devices such as an ion trap and a time-of-flight mass filter.

[0092] [plan]

[0093] It is obvious to those skilled in the art that the above-described exemplary embodiments are specific examples of the following aspects.

[0094] (Item 1)

[0095] A mass analysis method according to one embodiment of the present invention is:

[0096] A mass spectrometry method comprises performing MS scan measurement of a target compound, selecting one or more precursor ion candidates from ions detected by the MS scan measurement based on a predetermined first criterion related to the measurement intensity,

[0097] performing MS / MS scan measurement using each of the one or more precursor ion candidates, and selecting product ion candidates from product ions detected by the MS / MS scan measurement based on a predetermined second criterion related to the measurement intensity;

[0098] The group of the precursor ion candidate and the product ion candidate is determined as an MRM transition, wherein,

[0099] In the MS scan measurement and / or the MS / MS scan measurement, the mass resolution at a larger mass-to-charge ratio or mass-to-charge ratio range is made lower than the mass resolution at a smaller mass-to-charge ratio or mass-to-charge ratio range in such a manner that the measurement sensitivity at the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

[0100] (Item 7)

[0101] Another aspect of the mass spectrometry method of the present invention is:

[0102] A mass analysis method comprises performing MS scan measurement of a target compound and selecting one or more target ion candidates from ions detected by the MS scan measurement based on a predetermined criterion related to the measurement intensity, wherein:

[0103] In the MS scan measurement, the mass resolution at a larger mass-to-charge ratio or within a mass-to-charge ratio range is made lower than that at a smaller mass-to-charge ratio or within a mass-to-charge ratio range so that the measurement sensitivity within the larger mass-to-charge ratio or within the mass-to-charge ratio range becomes higher.

[0104] (Item 8)

[0105] A mass spectrometer according to one embodiment of the present invention includes:

[0106] a precursor ion candidate determination unit that performs MS scan measurement of a target compound and selects one or more precursor ion candidates from ions detected by the MS scan measurement based on a predetermined first criterion related to measurement intensity;

[0107] a product ion candidate determining unit that performs MS / MS scan measurement using each of the one or more precursor ion candidates and selects a product ion candidate from product ions detected by the MS / MS scan measurement based on a predetermined second criterion related to the measurement intensity;

[0108] an MRM transition determining unit that determines a set of the precursor ion candidate and the product ion candidate as an MRM transition;

[0109] The mass resolution setting unit makes the mass resolution in a larger mass-to-charge ratio or mass-to-charge ratio range lower than the mass resolution in a smaller mass-to-charge ratio or mass-to-charge ratio range in the MS scan measurement and / or the MS / MS scan measurement in such a manner that the measurement sensitivity in the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

[0110] (Item 9)

[0111] A mass spectrometer according to another embodiment of the present invention includes:

[0112] a target ion determination unit that performs MS scan measurement of a target compound and determines one or more target ions from ions detected by the MS scan measurement based on a predetermined criterion related to the measurement intensity;

[0113] The mass resolution setting unit makes the mass resolution at a larger mass-to-charge ratio or mass-to-charge ratio range lower than the mass resolution at a smaller mass-to-charge ratio or mass-to-charge ratio range in the MS scan measurement so that the measurement sensitivity at the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

[0114] In the mass analysis methods of items 1 and 7, and the mass analysis devices of items 8 and 9, when performing MS scan measurements and / or MS / MS scan measurements, the mass resolution within a larger mass-to-charge ratio or mass-to-charge ratio range is lowered than the mass resolution within a smaller mass-to-charge ratio or mass-to-charge ratio range in such a way that the measurement sensitivity within the larger mass-to-charge ratio or mass-to-charge ratio range is increased. There are various methods for reducing mass resolution, but in the mass analysis methods of items 1 and 7, and the mass analysis devices of items 8 and 9, the mass resolution is not simply reduced, but is reduced in a manner associated with improving measurement sensitivity. Therefore, compared with the past, it is easier to select ions with a large mass-to-charge ratio as MRM transition or target ions. Compared with ions with a small mass-to-charge ratio, ions with a large mass-to-charge ratio are larger in themselves and often have characteristic structures in the target compound.

[0115] In the mass spectrometry methods of items 1 and 7, and the mass spectrometry apparatuses of items 8 and 9, since ions with a characteristic structure and high compound selectivity in the target compound are determined as MRM transition or target ions, even when measuring a sample containing the target compound and an impurity compound with similar structures and characteristics, only the target compound can be measured. In addition, by determining ions with a large mass-to-charge ratio as MRM transition or target ions, the influence of ions and noise from the mobile phase is reduced in MRM measurements or SIM measurements. Therefore, the target compound can be accurately analyzed. In addition, the first and second benchmarks in the present invention may be the same or different.

[0116] (Item 2)

[0117] The quality analysis method of item 2 is, in the quality analysis method of item 1,

[0118] In the MS scanning measurement and / or the MS / MS scanning measurement, after multiplying the measured intensity of each ion within the larger mass-to-charge ratio or mass-to-charge ratio range by a predetermined coefficient greater than 1, a specified number of ions are determined as the precursor ion candidates and / or the product ion candidates in order of measured intensity from high to low.

[0119] In the mass spectrometry method of the second item, by appropriately setting the aforementioned predetermined coefficients, ions having a large mass-to-charge ratio can be easily and preferentially selected as precursor ion candidates and product ion candidates.

[0120] (Item 3)

[0121] The quality analysis method of item 3 is that, in the quality analysis method of item 1 or 2,

[0122] At the larger mass-to-charge ratio or mass-to-charge ratio range, the mass resolution is reduced by making the range over which the measured intensities are added, ie, the mass window, larger than that at the smaller mass-to-charge ratio or mass-to-charge ratio range.

[0123] (Item 4)

[0124] The mass analysis method of item 4 is, in any one of the mass analysis methods of items 1 to 3,

[0125] In the larger mass-to-charge ratio or mass-to-charge ratio range, the mass separation capability in the mass separation section that separates the ions by mass is reduced, thereby increasing the transmittance of the ions and reducing the mass resolution.

[0126] As a method of making the mass resolution at a larger mass-to-charge ratio or within a mass-to-charge ratio range higher with the measurement sensitivity within the larger mass-to-charge ratio or within the mass-to-charge ratio range, lower than the mass resolution at a smaller mass-to-charge ratio or within the mass-to-charge ratio range, for example, the following method can be used: as described in item 3, at a larger mass-to-charge ratio or within the mass-to-charge ratio range, the range over which the measurement intensities are added, i.e., the mass window, is made larger than the smaller mass-to-charge ratio or within the mass-to-charge ratio range; as described in item 4, at a larger mass-to-charge ratio or within the mass-to-charge ratio range, the transmittance of the ions is increased by reducing the mass separation capacity in the mass separation section that performs mass separation on the ions.

[0127] (Item 5)

[0128] The mass analysis method of item 5 is, in any one of the mass analysis methods of items 1 to 4,

[0129] When selecting the precursor ion candidates and / or the product ion candidates, ions whose mass-to-charge ratio differs from the previously selected ions within a predetermined range are excluded, and other candidates are selected.

[0130] In the mass analysis method of item 5, repeated selection of multiple identical ions or ions with similar structures as precursor ion candidates and product ion candidates can be avoided, thereby determining MRM transitions with higher compound selectivity.

[0131] (Item 6)

[0132] The mass analysis method of item 6 is, in any one of the mass analysis methods of items 1 to 5,

[0133] Determine the MRM transition for each of the multiple target compounds, and then

[0134] For MRM transitions including precursor ion candidates and / or product ion candidates with similar mass-to-charge ratios between different compounds, the fact that the mass-to-charge ratio is close to that of the MRM transitions of other compounds is noted.

[0135] In the mass spectrometry method of item 6, when analyzing a sample containing multiple compounds having similar mass-to-charge ratios of precursor ions and / or product ions contained in the MRM transition, the annotation can draw attention to the fact that the MRM transition has low selectivity for the multiple compounds, thereby avoiding the incorrect identification of these compounds or errors in quantitative values.

[0136] Description of Reference Numerals

[0137] 1Mass analysis device

[0138] 10Quality Analysis Department

[0139] 11 Ionization chamber

[0140] 111ESI probe

[0141] 121st intermediate vacuum chamber

[0142] 121 ion guide

[0143] 122 cone hole body

[0144] 13. Second intermediate vacuum chamber

[0145] 131 ion guide

[0146] 14 Analysis Room

[0147] 15 front stage quadrupole mass filter

[0148] 151 Anterior Rod Electrode

[0149] 152 main rod electrode

[0150] 153 rear rod electrode

[0151] 16 collision cells

[0152] 161 Multipole Ion Guide

[0153] 17 post-stage quadrupole mass filter

[0154] 171 Anterior Rod Electrode

[0155] 172 main rod electrode

[0156] 18 ion detectors

[0157] 40 Control and Processing Department

[0158] 41 Storage Department

[0159] 42 Measurement condition setting unit

[0160] 421 Mass resolution setting unit

[0161] 422 Weighting Setting Unit

[0162] 43 Measurement Execution Department

[0163] 44 Precursor ion candidate determination unit

[0164] 45 Product ion candidate determination unit

[0165] 46 MRM Transition Decision Department

[0166] 47 Target ion determination unit

[0167] 5 Input section

[0168] 6 Display unit

[0169] C ion optical axis.

Claims

1. A quality analysis method, characterized in that performing MS scan measurement of the target compound, and selecting one or more precursor ion candidates from ions detected by the MS scan measurement based on a predetermined first criterion related to the measurement intensity; performing MS / MS scan measurement using each of the one or more precursor ion candidates, and selecting product ion candidates from product ions detected by the MS / MS scan measurement based on a predetermined second criterion related to the measurement intensity; determining a set of the precursor ion candidate and the product ion candidate as an MRM transition, In the MS scan measurement and / or the MS / MS scan measurement, the mass resolution at a larger mass-to-charge ratio or mass-to-charge ratio range is made lower than the mass resolution at a smaller mass-to-charge ratio or mass-to-charge ratio range in such a manner that the measurement sensitivity at the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

2. The mass analysis method according to claim 1, wherein In the MS scanning measurement and / or the MS / MS scanning measurement, after multiplying the measured intensity of each ion within the larger mass-to-charge ratio or mass-to-charge ratio range by a predetermined coefficient greater than 1, a specified number of ions are determined as the precursor ion candidates and / or the product ion candidates in order of measured intensity from high to low.

3. The mass analysis method according to claim 1, wherein At the larger mass-to-charge ratio or mass-to-charge ratio range, the mass resolution is reduced by making the range over which the measured intensities are added, ie, the mass window, larger than that at the smaller mass-to-charge ratio or mass-to-charge ratio range.

4. The mass analysis method according to claim 1, wherein In the larger mass-to-charge ratio or mass-to-charge ratio range, the mass separation capability in the mass separation section that separates the ions by mass is reduced, thereby increasing the transmittance of the ions and reducing the mass resolution.

5. The mass analysis method according to claim 1, wherein When selecting the precursor ion candidates and / or the product ion candidates, ions whose mass-to-charge ratio differs from the previously selected ions within a predetermined range are excluded, and other candidates are selected.

6. The mass analysis method according to claim 1, wherein Determine the MRM transition for each of the multiple target compounds, and then For MRM transitions including precursor ion candidates and / or product ion candidates with similar mass-to-charge ratios between different compounds, the fact that the mass-to-charge ratio is close to that of the MRM transitions of other compounds is noted.

7. A quality analysis method, characterized in that Performing MS scan measurement of the target compound, selecting one or more target ion candidates from ions detected by the MS scan measurement based on a predetermined criterion related to the measurement intensity, In the MS scan measurement, the mass resolution at a larger mass-to-charge ratio or within a mass-to-charge ratio range is made lower than that at a smaller mass-to-charge ratio or within a mass-to-charge ratio range so that the measurement sensitivity within the larger mass-to-charge ratio or within the mass-to-charge ratio range becomes higher.

8. A mass analysis device, characterized in that have: a precursor ion candidate determination unit that performs MS scan measurement of a target compound and selects one or more precursor ion candidates from ions detected by the MS scan measurement based on a predetermined first criterion related to measurement intensity; a product ion candidate determining unit that performs MS / MS scan measurement using each of the one or more precursor ion candidates and selects a product ion candidate from product ions detected by the MS / MS scan measurement based on a predetermined second criterion related to the measurement intensity; an MRM transition determining unit that determines a set of the precursor ion candidate and the product ion candidate as an MRM transition; The mass resolution setting unit makes the mass resolution in a larger mass-to-charge ratio or mass-to-charge ratio range lower than the mass resolution in a smaller mass-to-charge ratio or mass-to-charge ratio range in the MS scan measurement and / or the MS / MS scan measurement in such a manner that the measurement sensitivity in the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

9. A mass analysis device, characterized in that have: a target ion determination unit that performs MS scan measurement of a target compound and determines one or more target ions from ions detected by the MS scan measurement based on a predetermined criterion related to the measurement intensity; The mass resolution setting unit makes the mass resolution in a larger mass-to-charge ratio or mass-to-charge ratio range lower than the mass resolution in a smaller mass-to-charge ratio or mass-to-charge ratio range in the MS scan measurement and / or the MS / MS scan measurement in such a manner that the measurement sensitivity in the larger mass-to-charge ratio or mass-to-charge ratio range becomes higher.

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