Mass spectrometry method and mass spectrometer

Abstract

To integrate mass analysis data acquired by dividing the range of mass-to-charge ratio of a measurement object into multiple sections and obtain mass analysis data the measurement sensitivity of which is uniform.SOLUTION: The present invention includes: setting a plurality of partial mass-to-charge ratio ranges so that partial mass-to-charge ratio ranges which are adjacent in the mass-to-charge ratio of reference ion overlap each other (step 2); acquiring the mass analysis data of a known compound in each partial mass-to-charge ratio range (steps 3, 4); determining a normalization coefficient on the basis of the measured intensity of the reference ion in the mass analysis data of adjacent partial mass-to-charge ratio ranges (steps 6, 9); acquiring the mass analysis data of a measurement object sample in each partial mass-to-charge ratio range (step 12); multiplying the normalization coefficient to the mass analysis data of the measurement object sample acquired in each partial mass-to-charge ratio range so as to normalize the mass analysis data (step 14); and integrating the mass analysis data of a plurality of partial mass-to-charge ratio ranges after normalization into one mass analysis data (step 15).SELECTED DRAWING: Figure 2

Description

[Technical field]

[0001] The present invention relates to a mass spectrometry method and a mass spectrometry apparatus. [Background technology]

[0002] In a time-of-flight mass spectrometer (TOF-MS), a group of ions derived from sample components is introduced into a time-of-flight mass separation section, and the ions are given a certain kinetic energy to enter a drift space, and the ions are detected by an ion detector after flying a predetermined distance along an orbit. In the drift space, ions with a smaller mass-to-charge ratio fly faster and enter the ion detector in a shorter time. Therefore, a graph is created with the flight time on the horizontal axis and the ion intensity on the vertical axis, and the flight time is converted to the mass-to-charge ratio based on previously prepared information to obtain a mass spectrum. In a time-of-flight mass spectrometer, for example, a quadrupole electrode (QP) or an ion trap (IT) is provided in front of the time-of-flight mass analysis section. The quadrupole electrode transports the ions to the time-of-flight mass separation section, and the ion trap accumulates the ions and ejects them all at once into the drift space (Patent Documents 1 and 2).

[0003] A time-of-flight mass spectrometer can measure ions over a wide range of mass-to-charge ratios (m / z) (e.g., m / z=500-20,000). However, the range of mass-to-charge ratios of ions that can be stored in an ion trap is limited, and the range of mass-to-charge ratios of ions that can be transported by a quadrupole electrode is also limited. In addition, the output signal from the ion detector is converted into digital form by a digitizer, but the storage capacity of the digitizer is limited, and it is not possible to store a huge amount of digitally converted data over a wide range of mass-to-charge ratios. For these reasons, it is not possible to measure a wide range of mass-to-charge ratios at once. Therefore, when acquiring mass spectrometry data over a wide range of mass-to-charge ratios, it is necessary to divide the mass-to-charge ratio range of the measurement target into multiple parts, perform a measurement for each of the divided mass-to-charge ratio ranges, and integrate the mass spectra acquired in each measurement. [Prior art documents] [Patent documents]

[0004] [Patent Document 1] International Publication No. 2019 / 220501 [Patent Document 2] International Publication No. 2021 / 131140 [Non-patent literature]

[0005] [Non-Patent Document 1] Noam Kishenbaum, Izhak Michaelevskim, Mical Sharon, "Analayzing Large Protein Complexes by Structural Mass Spectroscopy", J Vis. Exp. 2010 Jun 19,(40),1954 Summary of the Invention [Problem to be solved by the invention]

[0006] In the measurement for each mass-to-charge ratio range after division, a different voltage is applied to the ion trap or quadrupole electrodes for each mass-to-charge ratio range to capture or pass ions in that mass-to-charge ratio range. Since the measurement sensitivity of ions varies depending on the value of the voltage applied to the ion trap or quadrupole electrodes, even if the mass spectra obtained for each mass-to-charge ratio range after division are directly integrated, the measurement sensitivity differs for each mass-to-charge ratio range, and mass spectrometry data with uniform measurement sensitivity cannot be obtained as in the case of measuring the entire mass-to-charge ratio range at once.

[0007] The problem that the present invention aims to solve is to provide a technology that can obtain mass spectrometry data with uniform measurement sensitivity by dividing the mass-to-charge ratio range of the measurement target into multiple parts, performing mass spectrometry in each of the divided mass-to-charge ratio ranges, and integrating the mass spectrometry data obtained. [Means for solving the problem]

[0008] In order to solve the above problems, one aspect of the mass spectrometry method according to the present invention comprises the steps of: dividing the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratios of predetermined reference ions generated from known compounds; performing mass spectrometry on the known compounds in each of the plurality of partial mass-to-charge ratio ranges to obtain mass spectrometry data; determining a normalization factor for normalizing the measured intensities of the ions in each of the plurality of partial mass-to-charge ratio ranges based on the measured intensities of the reference ions in the mass spectrometry data acquired in each of the adjacent partial mass-to-charge ratio ranges; obtaining mass spectrometry data by performing mass spectrometry on the measurement target sample in each of the plurality of partial mass-to-charge ratio ranges; normalizing the mass spectrometry data by multiplying the measured intensities of ions in the mass spectrometry data of the measurement target sample acquired in each of the plurality of partial mass-to-charge ratio ranges by a normalization coefficient corresponding to the partial mass-to-charge ratio range; The mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization is integrated into one mass spectrometry data. It is something.

[0009] In order to solve the above problems, one aspect of the mass spectrometer according to the present invention is to a memory unit storing a plurality of partial mass-to-charge ratio ranges obtained by dividing the mass-to-charge ratio range of a measurement target such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratio of a predetermined reference ion generated from a known compound, and a normalization coefficient for each of the plurality of partial mass-to-charge ratio ranges, the normalization coefficient being determined based on the measured intensity of the reference ion in mass spectrometry data acquired in each of the adjacent partial mass-to-charge ratio ranges; a measurement execution unit that acquires mass spectrometry data by performing mass spectrometry on a measurement target sample in each of the plurality of partial mass-to-charge ratio ranges; a data normalization unit that normalizes the mass spectrometry data by multiplying the measured intensities of ions in the mass spectrometry data of the sample to be measured, which are acquired in each of the plurality of partial mass-to-charge ratio ranges, by a normalization coefficient corresponding to the corresponding partial mass-to-charge ratio range; a data integration unit that integrates the mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization into one mass spectrometry data; Equipped with.

[0010] Another aspect of the mass spectrometry method according to the present invention, which has been made to solve the above problems, comprises: dividing the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratios of predetermined reference ions generated from known compounds; obtaining mass spectrometry data by performing mass spectrometry on a measurement sample to which the known compound has been added in each of the plurality of partial mass-to-charge ratio ranges; normalizing the mass spectrometry data by multiplying the measured intensities of ions in the mass spectrometry data of each of the plurality of partial mass-to-charge ratio ranges by a constant so that the measured intensities of the reference ion in the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges are uniform; The mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization is integrated into one mass spectrometry data. It is something.

[0011] Another aspect of the mass spectrometer according to the present invention, which has been made to solve the above problems, is a partial mass-to-charge ratio range setting unit that divides the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratio of a predetermined reference ion generated from a known compound; a measurement execution unit that performs mass spectrometry on a measurement target sample to which the known compound has been added in each of the plurality of partial mass-to-charge ratio ranges to obtain mass spectrometry data; a data normalization unit that normalizes the mass spectrometry data by multiplying the measured intensities of ions in each of the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges by a constant so that the measured intensities of the reference ion in the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges are uniform; a data integration unit that integrates the mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization into one mass spectrometry data; Equipped with. Effect of the Invention

[0012] In the present invention, the mass-to-charge ratio range of the measurement target is divided into a plurality of partial mass-to-charge ratio ranges by the mass-to-charge ratio of a predetermined reference ion generated from a known compound so that adjacent partial mass-to-charge ratio ranges overlap. When the mass analysis to be performed is an MS analysis, the reference ion is an ion generated directly from the known compound, and when the mass analysis is an MS / MS analysis, the reference ion is an ion generated from the known compound or an ion (product ion) generated by dissociation of the ion (precursor ion). Here, if the number of partial mass-to-charge ratio ranges is n, the number of reference ions is n-1 (n is a positive integer). Therefore, when the number of partial mass-to-charge ratio ranges is 2, only one type of reference ion is used, and when the number of partial mass-to-charge ratio ranges is 3 or more, multiple types of reference ions are used. Then, mass analysis is performed on the measurement target sample to which the known compound or the known compound has been added in each of the multiple partial mass-to-charge ratio ranges to obtain mass analysis data.

[0013] After acquiring mass spectrometry data corresponding to each partial mass-to-charge ratio range, a normalization coefficient is determined for each of the plurality of partial mass-to-charge ratio ranges based on the measured intensities of reference ions in adjacent partial mass-to-charge ratio ranges. In the present invention, the normalization coefficient is determined so that the measured intensities of the reference ions commonly measured for adjacent partial mass-to-charge ratio ranges are uniform, thereby making the measurement sensitivity of ions in the plurality of partial mass-to-charge ratio ranges uniform. Therefore, by integrating the mass spectrometry data corresponding to the plurality of partial mass-to-charge ratio ranges after normalization, it is possible to obtain mass spectrometry data with uniform measurement sensitivity throughout the entire mass-to-charge ratio range of the measurement target. [Brief description of the drawings]

[0014] [Figure 1] 1 is a diagram showing the configuration of a main part of an embodiment of a mass spectrometer according to the present invention; [Diagram 2] 4 is a flowchart illustrating the procedure of a calibration mode which is one embodiment of a mass spectrometry method according to the present invention. [Diagram 3] 4 shows the mass-to-charge ratio of ions generated from cesium iodide, which is the standard material in this embodiment. [Figure 4] FIG. 4 is a diagram for explaining partial mass-to-charge ratio ranges A to C in the present embodiment. [Diagram 5] FIG. 2 is a diagram for explaining ions commonly measured in adjacent partial mass-to-charge ratio ranges. [Figure 6] FIG. 13 is a diagram for explaining normalization of a partial mass-to-charge ratio range B. [Figure 7] FIG. 13 is a diagram for explaining normalization of a partial mass-to-charge ratio range C. [Figure 8] 6 is a flowchart for explaining a procedure for measuring a real sample after executing a calibration mode in this embodiment. [Figure 9] FIG. 4 is a diagram for explaining a process of creating mass spectrum data by integrating graph data of partial mass-to-charge ratio ranges A to C. [Figure 10] 4 is a flowchart illustrating the procedure of an actual sample analysis mode, which is one embodiment of a mass spectrometry method according to the present invention. DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS

[0015] DETAILED DESCRIPTION OF THE PREFERRED EMBODIMENTS Hereinafter, embodiments of a mass spectrometry method and a mass spectrometry apparatus according to the present invention will be described with reference to the drawings.

[0016] 1 shows the main configuration of a liquid chromatograph mass spectrometer 1 in this embodiment. The liquid chromatograph mass spectrometer 1 in this embodiment includes a liquid chromatograph (LC) 10, a mass spectrometer 20, and a control / processing unit 40 that controls the operations of these. The liquid chromatograph 10 separates various components contained in a liquid sample using a column, and introduces the components into an electrospray ionization (ESI) probe 211.

[0017] The interior of the mass spectrometer 20 is partitioned into an ionization chamber 21, a first intermediate vacuum chamber 22, a second intermediate vacuum chamber 23, and an analysis chamber 24. The ionization chamber 21 is at approximately atmospheric pressure, and is equipped with an electrospray ionization (ESI) probe 211. The first intermediate vacuum chamber 22, the second intermediate vacuum chamber 23, and the analysis chamber 24 are provided within a vacuum chamber, and have a differential pumping system configuration in which the degree of vacuum increases in this order.

[0018] A partition is provided between the ionization chamber 21 and the first intermediate vacuum chamber 22, and they communicate with each other through a desolvation tube 212 provided in the partition. The first intermediate vacuum chamber 22 is provided with an ion guide 221 that transports the ions generated in the ionization chamber 21 to a subsequent stage while converging them along an ion optical axis C, which is the central axis of the ion flight direction.

[0019] The first intermediate vacuum chamber 22 and the second intermediate vacuum chamber 23 communicate with each other through a small hole formed at the top of the skimmer cone 222 that separates them. The second intermediate vacuum chamber 23 is also provided with an ion guide 231 that transports ions entering from the first intermediate vacuum chamber 22 to a subsequent stage while converging them along the ion optical axis C.

[0020] The second intermediate vacuum chamber 23 and the analysis chamber 24 communicate with each other through a small hole formed in the partition. The analysis chamber is provided with a quadrupole electrode 241, a collision cell 242, a linear ion trap 244, a multi-turn time-of-flight mass separator 245, and an ion detector 247. The quadrupole electrode 241 focuses ions having a mass-to-charge ratio within the measurement range along the ion optical axis C and transports them to a subsequent stage. A multipole ion guide 243 is disposed inside the collision cell 242. An inert gas is supplied to the collision cell 242 at an appropriate timing from a collision-induced dissociation (CID) gas source (not shown) disposed outside the vacuum chamber.

[0021] The linear ion trap 244 includes a front electrode 2441 having an ion introduction aperture formed on the ion optical axis C, a back electrode 2442, and four rod electrodes 2443 arranged along the ion optical axis C so as to surround the ion optical axis C. One of the rod electrodes 2443 has a slit 2444 for ejecting ions.

[0022] Outside the slit 2444, the multi-turn time-of-flight mass separator 245 is disposed. The multi-turn time-of-flight mass separator 245 includes an ion inlet 2451, a rotation section 246, and an ion outlet 2452. The ion inlet 2451 is disposed opposite the slit 2444 of the rod electrode 2443. The rotation section 246 has an outer electrode 2461 having a substantially spheroidal shape, and an inner electrode 2462 having a substantially spheroidal shape provided inside the outer electrode 2461. FIG. 1 shows a ZX cross-sectional view including the Z axis, which is the rotation axis of the substantially spheroid of the outer electrode 2461 and the inner electrode 2462, and the X axis, which is an axis in one direction perpendicular to the Z axis. When the rotation section 246 is cut on a plane including the Z axis, it has a shape substantially the same as that shown in FIG. 1, regardless of the azimuth angle of the cross section (angle around the Z axis). The outer electrode 2461 and the inner electrode 2462 are configured with a partial electrode pair in which a pair of electrodes that are curved in the ZX plane face each other, and a partial electrode pair in which a pair of electrodes that are linear in the ZX plane face each other. An ion detector 247 is disposed outside the ion outlet 2452.

[0023] The control / processing unit 40 includes a memory unit 41. The memory unit 41 stores measurement conditions and analysis conditions for various known compounds. The information on the known compounds includes retention times for standard substances that are candidates for use in the calibration mode and real sample analysis mode described below, and information on the mass-to-charge ratios of ions generated from the standard substances. Furthermore, the memory unit 41 stores information on partial mass-to-charge ratio ranges and normalization coefficients determined in the calibration mode and real sample analysis mode.

[0024] The control / processing unit 40 also includes, as functional blocks, a mode selection unit 51, a standard material determination unit 52, a partial mass-to-charge ratio range setting unit 53, a measurement execution unit 54, a data creation unit 55, a normalization coefficient calculation unit 56, a data normalization unit 57, and a data integration unit 58. The actual substance of the control / processing unit 40 is a general personal computer, to which an input unit 6 through which a user inputs appropriate information and a display unit 7 for displaying appropriate information are connected. Moreover, the above functional blocks are embodied by executing a pre-installed mass analysis program on the processor.

[0025] Next, the mass spectrometry method according to this embodiment will be described.

[0026] In the mass spectrometry method of this embodiment, first, the mode selection unit 51 displays a mode selection screen on the display unit 7 and allows the user to select an analysis mode. The analysis modes include a calibration mode and an actual sample analysis mode.

[0027] First, a case where the user selects the calibration mode will be described. FIG. 2 is a flow chart relating to the calibration mode. The calibration mode is performed, for example, by the manufacturer when the liquid chromatograph mass spectrometer 1 is shipped or installed. Alternatively, the calibration mode is performed by the user of the liquid chromatograph mass spectrometer 1 after parts of the mass spectrometer 20 are replaced or settings of each section are changed, or during periodic maintenance. When the calibration mode is performed by the user of the liquid chromatograph mass spectrometer 1, a measurement execution unit 54 described later corresponds to the second measurement execution unit in the present invention.

[0028] When the calibration mode is started, the standard material determination unit 52 displays a screen for inputting information about the standard material on the display unit 7, and determines a standard material that generates a plurality of ions in the mass-to-charge ratio range for which calibration is to be performed (step 1). For example, a list of standard material candidates stored in the storage unit 41 may be displayed together with information about the mass-to-charge ratio of ions generated from each standard material, and the user may select from the list. Alternatively, the user may input the name of the standard material and information about the mass-to-charge ratio of ions generated from the standard material. For example, CsI (cesium iodide) may be used as such a standard material. As described in Non-Patent Document 1, cluster ions are generated from CsI at equal mass-to-charge ratio intervals in a wide mass-to-charge ratio range from 393 to over 10,000. FIG. 3 shows the mass-to-charge ratios of ions generated from CsI.

[0029] In a time-of-flight mass spectrometer such as that of this embodiment, ions can be measured in a wide range of mass-to-charge ratios (m / z) (for example, m / z=500 to 20,000). However, the range of mass-to-charge ratios of ions that can be stored in the linear ion trap 244 is limited, and the range of mass-to-charge ratios of ions that can be transported by the quadrupole electrode 241 is also limited. In addition, the output signal from the ion detector 247 is converted into digital form by a digitizer, but the storage capacity of the digitizer is limited, and it is not possible to store a huge amount of digitally converted data over a wide range of mass-to-charge ratios. In particular, in the multi-turn time-of-flight mass separator 245 of this embodiment, the mass resolution can be improved by lengthening the flight distance of ions, but on the other hand, the number of sampling times increases, and the data capacity increases. For these reasons, it is not possible to measure a wide range of mass-to-charge ratios at once, so when acquiring mass analysis data over a wide range of mass-to-charge ratios, the mass-to-charge ratio range of the measurement target is divided into a plurality of parts, a measurement is performed for each of the divided mass-to-charge ratio ranges, and the mass spectra acquired in each measurement are integrated.

[0030] When the standard material is determined, the partial mass-to-charge ratio range setting unit 53 allows the user to set the mass-to-charge ratio range for performing the calibration. In this example, the range of 500-10,800 is set as the mass-to-charge ratio range. The partial mass-to-charge ratio range setting unit 53 also displays on the display unit 7 a screen for allowing the user to divide the set mass-to-charge ratio range into a plurality of partial mass-to-charge ratio ranges (step 2). The sizes (widths) of the plurality of partial mass-to-charge ratio ranges are determined so that ions can be transported by the quadrupole electrode 241 under one applied voltage condition, ions can be trapped in the linear ion trap 244 under one applied voltage condition, and the amount of data acquired by the ion detector 247 in one measurement falls within a range that can be stored in the digitizer. Adjacent partial mass-to-charge ratio ranges are also partially overlapped so that the mass-to-charge ratio of ions generated from the standard material is included in that portion.

[0031] In this example, three partial mass-to-charge ratio ranges A to C are set as shown in Fig. 4. The partial mass-to-charge ratio range A is m / z = 500-1,500, the partial mass-to-charge ratio range B is m / z = 1,300-3,900, and the partial mass-to-charge ratio range C is m / z = 3,600-10,800. The partial mass-to-charge ratio range A and the partial mass-to-charge ratio range B are (CsI)5Cs + The mass-to-charge ratio range B and the mass-to-charge ratio range C overlap in the range m / z = 1,300-1,500, which includes the mass-to-charge ratio of (CsI) 14 Cs + The partial mass-to-charge ratio ranges overlap in the range m / z=3,600-3,900, which includes the mass-to-charge ratio (m / z=3,770) of the first ion beam. The number of partial mass-to-charge ratio ranges may be two, or may be four or more.

[0032] When the partial mass-to-charge ratio ranges are set and the user sets a standard material and issues an instruction to start measurement, the measurement execution unit 54 measures the same amount of standard material in each of the determined three partial mass-to-charge ratio ranges A to C (step 3). When measuring the standard material, it may be introduced into the mass spectrometer 20 via the liquid chromatograph 10, or may be directly introduced into the ESI probe 211 of the mass spectrometer 20. In the mass spectrometer 20, for example, all ions within the partial mass-to-charge ratio range are transported by the quadrupole electrode 241 or the like, trapped once in the linear ion trap 244, and then ejected into the drift space for measurement. Note that since there is a nonlinear relationship between the time required for an ion to fly a predetermined distance defined in the orbiting unit 246 of the multi-turn time-of-flight mass separator 245 and the mass-to-charge ratio, the time intervals for sampling data during measurement in each of the partial mass ranges (the length of time for accumulating the intensity of the ions) do not necessarily have to be the same. Even if the sampling interval is made longer in a partial mass-to-charge ratio range where the mass-to-charge ratio is large than in a partial mass-to-charge ratio range where the mass-to-charge ratio is small, ions can be measured with approximately the same mass resolution in these partial mass-to-charge ratio ranges.

[0033] In each of the partial mass-to-charge ratio ranges A to C, a voltage (radio frequency voltage and / or direct current voltage) suitable for transporting ions within that partial mass-to-charge ratio range is applied to the quadrupole electrodes 241, etc., and a voltage (radio frequency voltage and / or direct current voltage) suitable for trapping ions within that partial mass-to-charge ratio range is applied to the linear ion trap 244. In other words, the voltage values ​​applied to the quadrupole electrodes 241 and the linear ion trap 244 during measurement of the partial mass-to-charge ratio ranges A to C are different from one another. Therefore, even if ions are measured by the same measurement method in the partial mass-to-charge ratio ranges A to C, the measurement sensitivity is often not uniform. Therefore, in this embodiment, mass spectrometry data in the partial mass-to-charge ratio ranges A to C is normalized as follows.

[0034] After the measurement is completed, the data creation unit 55 creates graph data (time-of-flight-intensity spectrum data) with the time-of-flight on the horizontal axis and the ion intensity on the vertical axis for each of the plurality of partial mass-to-charge ratio ranges A to C (step 4).

[0035] Next, the normalization coefficient calculation unit 56 calculates the intensity value of the mass peak of the ion derived from the standard material that is commonly measured in the adjacent partial mass-to-charge ratio ranges. Specifically, first, from the graph data of the partial mass-to-charge ratio range A and the partial mass-to-charge ratio range B, the normalization coefficient calculation unit 56 calculates the intensity value of the mass peak of the ion derived from the standard material that is commonly measured in the two partial mass-to-charge ratio ranges A and B. + Calculate the intensity value of the mass peak (m / z = 1,432) of (CsI)5Cs in the partial mass-to-charge ratio range A (Step 5, see Figure 5). + The intensity value [peak-area_A-upper] of the mass peak (m / z=1,432) of (CsI)5Cs in the partial mass-to-charge ratio range B +A set of intensity values ​​[peak-area_B-lower] of the mass peak (m / z=1,432) of the mass peak A is obtained. In this embodiment, the area value of the mass peak is taken as the intensity value of the mass peak. It is also possible to take the height of the mass peak as the intensity of the mass peak, but as described above, due to the difference in the voltage applied to each part during measurement of the partial mass-to-charge ratio ranges A to C, the peaks may differ even if the area value is the same, and as a result, the peak heights may also differ. Therefore, it is preferable to take the area value of the peak as the intensity value of the mass peak.

[0036] The normalization coefficient calculation unit 56 calculates the normalization coefficients for the partial mass-to-charge ratio ranges A and B by calculating the ratio of the intensity values ​​of the pair (step 6). In this embodiment, the value of [peak-area_A-upper] / [peak-area_B-lower] is calculated as the normalization coefficient for the partial mass-to-charge ratio range B. The normalization coefficient for the partial mass-to-charge ratio range A, which is used as the reference in the normalization, is set to 1. The data normalization unit 57 then multiplies the intensity value of the graph data in the partial mass-to-charge ratio range B by the calculated normalization coefficient for the partial mass-to-charge ratio range B to normalize the graph data for the partial mass-to-charge ratio range B (step 7, see FIG. 6). This makes it possible to equalize the measurement sensitivity of the partial mass-to-charge ratio range A and the partial mass-to-charge ratio range B. Here, the normalization coefficient is determined so as to normalize the partial mass-to-charge ratio B with the partial mass-to-charge ratio range A as the reference, but other methods may be used. For example, when the (CsI)5Cs + Alternatively, a method may be adopted in which the normalization coefficients of the partial mass-to-charge ratio ranges A and B are determined so that the intensity value of the mass peak (m / z=1,432) of

[0037] The normalization coefficient calculation unit 56 also calculates the normalization coefficient (CsI) from the normalized data of the partial mass-to-charge ratio range B and the partial mass-to-charge ratio range C. 14 Cs + The intensity of the mass peak (m / z=3,770) of (CsI) is calculated (step 8). Here, as in the above, the area value of the mass peak is taken as the intensity of the mass peak. As a result, the intensity of the (CsI)14 Cs + The intensity value of the mass peak (m / z = 3,770) [peak-area_B-upper]' and the (CsI) 14 Cs + A set of intensity values ​​[peak-area_C-lower] of the mass peak (m / z=3,770) is obtained.

[0038] The normalization coefficient calculation unit 56 calculates the normalization coefficient by calculating the ratio of the intensity values ​​of the above pair (step 9). In this embodiment, the value of [peak-area_B-upper]' / [peak-area_C-lower] is calculated as the normalization coefficient of the partial mass-to-charge ratio range C. Then, the data normalization unit 57 normalizes the data of the partial mass-to-charge ratio range C by multiplying the calculated normalization coefficient by the intensity value of the graph data of the partial mass-to-charge ratio range C (step 10, FIG. 7). As a result, the measurement sensitivity of the partial mass-to-charge ratio range B and the partial mass-to-charge ratio range C after normalization is made uniform, and finally, the measurement sensitivity in all of the partial mass-to-charge ratios A to C is made uniform. In this embodiment, since three partial mass-to-charge ratio ranges A to C are set, the process of calculating the normalization coefficient from the intensity ratio is performed twice, but the number of times of this process varies depending on the number of set partial mass-to-charge ratio ranges. If it is only necessary to obtain the normalization coefficient of each partial mass-to-charge range during calibration, step 10 may be omitted.

[0039] The normalization coefficient values ​​for the partial mass-to-charge ratio ranges A to C calculated through the above process are stored in the storage unit 41 together with the mass-to-charge ratio ranges of each of the partial mass-to-charge ratio ranges A to C.

[0040] Next, the procedure for measuring the actual sample to be measured after the calibration mode has been executed will be described with reference to the flowchart of FIG.

[0041] First, the partial mass-to-charge ratio range setting unit 53 reads out information on the target ranges and normalization coefficients of a plurality of partial mass-to-charge ratio ranges A to C stored in the storage unit 41 (step 11).

[0042] When the user sets a real sample and issues an instruction to start measurement, the real sample is measured in each of the read partial mass-to-charge ratio ranges A to C (step 12), and graph data (time-of-flight-intensity spectrum data) is created (step 13) for each partial mass-to-charge ratio A to C, with the time-of-flight on the horizontal axis and the ion intensity on the vertical axis. When measuring the real sample, for example, a sample is introduced into liquid chromatograph 10, and measurements of the partial mass-to-charge ratio ranges A to C are repeatedly performed during the time period when the sample components separated in the column are introduced into mass spectrometer 20 (retention time of each component).

[0043] Next, the data normalization unit 57 multiplies each of the graph data of the partial mass-to-charge ratios A to C by the normalization coefficient read out from the storage unit 41 (step 14). Then, the data integration unit 58 integrates the graph data of the normalized partial mass-to-charge ratios A to C into one (step 15, see the upper part of FIG. 9). At this time, for the graph data of the overlapping region between the partial mass-to-charge ratio range A and the partial mass-to-charge ratio range B, and the graph data of the overlapping region between the partial mass-to-charge ratio range B and the partial mass-to-charge ratio range C, either one of the data may be used as is, or an average of the data of the overlapping regions may be used.

[0044] Finally, based on previously prepared information (information showing the relationship between the mass-to-charge ratio of ions and the time-of-flight), the time-of-flight on the horizontal axis of the integrated graph data is converted into mass-to-charge ratio to generate mass spectrum data (step 16, see the lower part of Figure 9). This makes it possible to obtain mass spectrum data with uniform measurement sensitivity over a wide range of mass-to-charge ratios.

[0045] Next, the case where the user selects the actual sample analysis mode will be described with reference to the flow chart of FIG.

[0046] When the real sample analysis mode is started, the standard material determination unit 52 displays a screen for inputting information about the standard material on the display unit 7, and determines a standard material that generates multiple ions in the mass-to-charge ratio range in which the real sample is measured (step 21). As in the above calibration mode, the standard material may be, for example, CsI (cesium iodide). The method of inputting the standard material may be the same as in the calibration mode.

[0047] Next, the partial mass-to-charge ratio range setting unit 53 prompts the user to set the mass-to-charge ratio range for performing the calibration, and divides the mass-to-charge ratio range into a plurality of partial mass-to-charge ratio ranges. In this example, as in the above, the range of 500-10,800 is set as the mass-to-charge ratio range, and three partial mass-to-charge ratio ranges A to C are set (step 22). The requirements for the plurality of partial mass-to-charge ratio ranges are the same as those in the calibration mode.

[0048] Once the partial mass-to-charge ratio ranges have been set and the user sets an actual sample to which a standard substance has been added and issues an instruction to start measurement, the measurement execution unit 54 measures the actual sample to which a standard substance has been added in each of the three determined partial mass-to-charge ratio ranges A to C (step 23).

[0049] After the measurement is completed, the data creation unit 55 creates graph data (time-of-flight-intensity spectrum data) with the time-of-flight on the horizontal axis and the ion intensity on the vertical axis for each of the plurality of partial mass-to-charge ratio ranges A to C (step 24).

[0050] Next, the process corresponding to steps 5 to 10 in the calibration mode is executed. That is, the normalization coefficient calculation unit 56 calculates the intensity value of the mass peak of the ion derived from the standard material measured in common in a plurality of adjacent partial mass-to-charge ratio ranges A and B (step 25), determines the ratio (step 26), and the data normalization unit 57 normalizes the graph data of the partial mass-to-charge ratio ranges A and B by multiplying them by a constant in accordance with the ratio (step 27). Next, the normalization coefficient calculation unit 56 calculates the intensity value of the mass peak of the ion derived from the standard material measured in common in a plurality of adjacent partial mass-to-charge ratio ranges B and C (step 28), determines the ratio between the intensity value in the partial mass-to-charge ratio range B after normalization and the intensity value in the partial mass-to-charge ratio range C (step 29), and the data normalization unit 57 normalizes the graph data of the partial mass-to-charge ratio range C by multiplying them by a constant in accordance with the ratio (step 30).

[0051] The data integrating unit 58 integrates the graph data of the normalized partial mass-to-charge ratios A to C into one (step 31). Again, for the graph data of the overlapping region between the partial mass-to-charge ratio range A and the partial mass-to-charge ratio range B, and the graph data of the overlapping region between the partial mass-to-charge ratio range B and the partial mass-to-charge ratio range C, either one of the data may be used as is, or an average of the data of the overlapping regions may be used.

[0052] Finally, based on previously prepared information (information showing the relationship between the mass-to-charge ratio of ions and the time-of-flight), the time-of-flight on the horizontal axis of the integrated graph data is converted into mass-to-charge ratio to generate mass spectrum data (step 32). This makes it possible to obtain mass spectrum data with uniform measurement sensitivity over a wide range of mass-to-charge ratios.

[0053] The above embodiment is an example, and can be appropriately modified in accordance with the gist of the present invention. Although the above embodiment is a liquid chromatograph mass spectrometer 1, the same configuration can be adopted in a gas chromatograph mass spectrometer or a mass spectrometer without a chromatograph. An appropriate ion source can be used depending on the sample to be measured. In the above embodiment, a linear ion trap is used to capture ions and simultaneously eject them into the drift space, but a three-dimensional ion trap may be used. Furthermore, in the above embodiment, a multi-turn time-of-flight mass analyzer is used, but one that makes ions fly in a straight line or one that makes them fly in a turn may be used. Alternatively, the present invention can be applied to a mass analyzer equipped with a mass separation unit other than a time-of-flight type, such as a quadrupole mass filter.

[0054] In the above embodiment, the measurement of mass spectrometry (MS analysis) of ions generated from a standard material or a real sample has been described, but the above-mentioned processing may be performed in the case of comprehensively measuring product ions generated by dissociating ions generated by introducing ions generated from the standard material or the real sample into the collision cell 242 without selecting those within each partial mass range (MS / MS analysis). Specifically, ions generated from the standard material or the real sample that have a mass-to-charge ratio within a predetermined mass-to-charge ratio range are collectively selected as precursor ions in the quadrupole electrode 241, and the precursor ions are dissociated in the collision cell 242 to generate product ions. Alternatively, ions generated from the standard material or the real sample that have a specific mass-to-charge ratio that has been determined in advance may be selected as precursor ions in the quadrupole electrode 241, and the precursor ions may be dissociated in the collision cell 242 to generate product ions. Then, as in the above embodiment, a plurality of partial mass-to-charge ratio ranges are set, and product ions in each of the plurality of partial mass-to-charge ratio ranges are captured by the linear ion trap 224 and ejected simultaneously into the drift space, and the product ions are measured in order of shortest flight time.

[0055] When dissociating ions, information on the mass-to-charge ratios of one or more product ions generated from a precursor ion derived from a standard substance (information corresponding to MRM transitions) is obtained in advance from the compound database, and mass spectrometry data for each partial mass-to-charge ratio range is normalized based on the intensity value of the mass peak of the product ion. Specifically, as the peak area shown in Figure 5-7, the area value of the mass peak of a product ion (reference ion) commonly included in adjacent partial mass-to-charge ratio ranges is obtained, and a normalization coefficient corresponding to each partial mass-to-charge ratio range is obtained so that the area values ​​match. When a precursor ion that has not been dissociated in the collision cell 242 is detected, the precursor ion itself may be used as a reference ion, and the mass spectrometry data may be normalized based on the intensity of its mass peak.

[0056] In the above embodiment, a standard material is selected, and then the mass-to-charge ratio range to be measured and a plurality of partial mass-to-charge ratio ranges obtained by dividing the selected range are set, but this order may be reversed. In that case, for example, the plurality of partial mass-to-charge ratio ranges set by the user may be collated with information on the standard material (information on the mass-to-charge ratio of the ions to be generated) stored in the memory unit 41, and one or more standard materials suitable for the plurality of partial mass-to-charge ratio ranges set may be displayed on the display unit 7, or, if there is no standard material suitable for the plurality of partial mass-to-charge ratio ranges set, a screen may be displayed on the display unit 7 to prompt the user to change the setting of the partial mass-to-charge ratio range.

[0057] In the above embodiment, the graph data in the partial mass-to-charge ratio ranges A to C, with the horizontal axis being the time of flight and the vertical axis being the measured intensity, was normalized, and finally the time of flight was converted into a mass-to-charge ratio to generate mass spectral data. However, the mass spectral data may be generated from the graph data acquired in the partial mass-to-charge ratio ranges A to C, and then the mass spectral data in each partial mass-to-charge ratio range A to C may be normalized.

[0058] In the above embodiment, the measurement data is normalized by calculating a normalization coefficient for the partial mass-to-charge ratio range B using the measurement data in the partial mass-to-charge ratio range A as a reference, and then the measurement data is normalized by calculating a normalization coefficient for the partial mass-to-charge ratio range C using the measurement data in the normalized partial mass-to-charge ratio range B as a reference, but the partial mass-to-charge ratio range used as the reference may be selected as appropriate. For example, in the above embodiment, when the partial mass-to-charge ratio range B is used as the reference, the normalization coefficients for the partial mass-to-charge ratio ranges A and C can be calculated and normalized simultaneously.

[0059] In the above embodiment, only one type of compound (cesium iodide) was used as the standard substance, but a mixture of multiple compounds may be used as the standard substance.

[0060] [Aspects] It will be apparent to those skilled in the art that the above-described exemplary embodiments are illustrative of the following aspects.

[0061] (Section 1) A mass spectrometry method according to one aspect of the present invention comprises the steps of: dividing the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratios of predetermined reference ions generated from known compounds; performing mass spectrometry on the known compounds in each of the plurality of partial mass-to-charge ratio ranges to obtain mass spectrometry data; determining a normalization factor for normalizing the measured intensities of the ions in each of the plurality of partial mass-to-charge ratio ranges based on the measured intensities of the reference ions in the mass spectrometry data acquired in each of the adjacent partial mass-to-charge ratio ranges; obtaining mass spectrometry data by performing mass spectrometry on the measurement target sample in each of the plurality of partial mass-to-charge ratio ranges; normalizing the mass spectrometry data by multiplying the measured intensities of ions in the mass spectrometry data of the measurement target sample acquired in each of the plurality of partial mass-to-charge ratio ranges by a normalization coefficient corresponding to the partial mass-to-charge ratio range; The mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization is integrated into one mass spectrometry data. It is something.

[0062] (Section 2) In addition, a mass spectrometry method according to another aspect of the present invention includes the steps of: dividing the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratios of predetermined reference ions generated from known compounds; obtaining mass spectrometry data by performing mass spectrometry on a measurement sample to which the known compound has been added in each of the plurality of partial mass-to-charge ratio ranges; normalizing the mass spectrometry data by multiplying the measured intensities of ions in the mass spectrometry data of each of the plurality of partial mass-to-charge ratio ranges by a constant so that the measured intensities of the reference ion in the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges are uniform; The mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization is integrated into one mass spectrometry data. It is something.

[0063] (Section 4) A mass spectrometer according to one aspect of the present invention comprises: a memory unit that stores a plurality of partial mass-to-charge ratio ranges obtained by dividing a mass-to-charge ratio range of a measurement target such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratio of a predetermined reference ion generated from a known compound, and a normalization coefficient for each of the plurality of partial mass-to-charge ratio ranges that is determined based on the measured intensity of the reference ion in mass spectrometry data acquired in each of the adjacent partial mass-to-charge ratio ranges; a measurement execution unit that acquires mass spectrometry data by performing mass spectrometry on a measurement target sample in each of the plurality of partial mass-to-charge ratio ranges; a data normalization unit that normalizes the mass spectrometry data by multiplying the measured intensities of ions in the mass spectrometry data of the sample to be measured, which are acquired in each of the plurality of partial mass-to-charge ratio ranges, by a normalization coefficient corresponding to the corresponding partial mass-to-charge ratio range; a data integration unit that integrates the mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization into one mass spectrometry data; Equipped with.

[0064] (Section 6) Furthermore, a mass spectrometer according to another aspect of the present invention comprises: a partial mass-to-charge ratio range setting unit that divides the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratio of a predetermined reference ion generated from a known compound; a measurement execution unit that performs mass spectrometry on a measurement target sample to which the known compound has been added in each of the plurality of partial mass-to-charge ratio ranges to obtain mass spectrometry data; a data normalization unit that normalizes the mass spectrometry data by multiplying the measured intensities of ions in each of the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges by a constant so that the measured intensities of the reference ion in the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges are uniform; a data integration unit that integrates the mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization into one mass spectrometry data; Equipped with.

[0065] In the mass spectrometry methods described in paragraphs 1 and 2 and the mass spectrometers described in paragraphs 4 and 6, the mass-to-charge ratio range of the measurement target is divided into a plurality of partial mass-to-charge ratio ranges by the mass-to-charge ratio of a predetermined reference ion generated from a known compound so that adjacent partial mass-to-charge ratio ranges overlap. If the mass spectrometry to be performed is an MS analysis, the reference ion is an ion generated directly from the known compound, and if the mass spectrometry to be performed is an MS / MS analysis, the reference ion is an ion generated from the known compound or an ion (product ion) generated by dissociation of the ion (precursor ion). Here, if the number of partial mass-to-charge ratio ranges is n, the number of reference ions is n-1 (n is a positive integer). Therefore, if the number of partial mass-to-charge ratio ranges is 2, only one type of reference ion is used, and if the number of partial mass-to-charge ratio ranges is 3 or more, multiple types of reference ions are used. Then, mass spectrometry is performed on the measurement target sample to which the known compound has been added in each of the multiple partial mass-to-charge ratio ranges to obtain mass spectrometry data.

[0066] After acquiring mass spectrometry data corresponding to each partial mass-to-charge ratio range, a normalization factor is determined for each of the plurality of partial mass-to-charge ratio ranges based on the measured intensities of reference ions in adjacent partial mass-to-charge ratio ranges. In the mass spectrometry methods described in paragraphs 1 and 2 and the mass spectrometry apparatuses described in paragraphs 4 and 6, the normalization factor is determined so that the measured intensities of the reference ions commonly measured for adjacent partial mass-to-charge ratio ranges are uniform, thereby uniformizing the measurement sensitivity of ions in the plurality of partial mass-to-charge ratio ranges. Therefore, by integrating the mass spectrometry data corresponding to the plurality of partial mass-to-charge ratio ranges after normalization, it is possible to obtain mass spectrometry data with uniform measurement sensitivity throughout the entire mass-to-charge ratio range of the measurement target.

[0067] (Section 3) The mass spectrometry method according to paragraph 3 is the mass spectrometry method according to paragraph 1 or 2, When integrating the mass spectrometry data, the mass spectrometry data of one partial mass-to-charge ratio range or the average value of the mass spectrometry data of two adjacent partial mass-to-charge ratio ranges is used as the mass spectrometry data corresponding to the overlapping partial mass-to-charge ratio ranges.

[0068] In the mass spectrometry method according to paragraph 1 or 2, as in the mass spectrometry method according to paragraph 3, mass spectrometry data corresponding to the overlapping partial mass-to-charge ratio ranges can be integrated into one by using mass spectrometry data of one partial mass-to-charge ratio range or an average value of mass spectrometry data of two adjacent partial mass-to-charge ratio ranges.

[0069] (Section 5) The mass spectrometer according to paragraph 5 is the mass spectrometer according to paragraph 4, further comprising: a partial mass-to-charge ratio range setting unit that divides the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges such that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratio of a predetermined reference ion generated from a known compound; a second measurement execution unit that acquires mass spectrometry data by performing mass spectrometry on the known compounds in each of the plurality of partial mass-to-charge ratio ranges; a normalization coefficient determining unit that determines a normalization coefficient for normalizing the measured intensities of the ions in the plurality of partial mass-to-charge ratio ranges based on the measured intensities of the reference ion in the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges, and stores the plurality of partial mass-to-charge ratio ranges and the normalization coefficients for each of the plurality of partial mass-to-charge ratio ranges in the storage unit. Equipped with.

[0070] In the mass spectrometer according to paragraph 5, a user of the apparatus can determine a plurality of partial mass-to-charge ratio ranges and normalization factors in addition to the partial mass-to-charge ratio ranges and normalization factors stored in the memory unit at the time of shipment of the apparatus.

[0071] (Section 7) The mass spectrometer according to paragraph 7 is a mass spectrometer according to any one of paragraphs 4 to 6, further comprising: A time-of-flight mass separator that makes the ions to be measured fly through a specified flight space. Equipped with.

[0072] In a configuration including a time-of-flight mass analyzer such as the mass analyzer according to the seventh aspect, ions can be measured in a wide range of mass-to-charge ratios (m / z) (for example, m / z=500 to 20,000). However, the range of mass-to-charge ratios of ions that can be stored in an ion trap is limited, and the range of mass-to-charge ratios of ions that can be transported by a quadrupole electrode is also limited. In addition, the output signal from the ion detector is converted into a digital signal by a digitizer, but the storage capacity of the digitizer is limited, and it is not possible to store a large amount of digitally converted data over a wide range of mass-to-charge ratios. In particular, a mass analyzer including a multi-turn time-of-flight mass separator has the characteristic of being able to increase the mass resolution by lengthening the flight time of ions and shortening the sampling interval of data, but the amount of data tends to be large. The mass analyzer according to any one of the fourth to sixth aspects can be suitably used in a configuration including a time-of-flight mass analyzer such as the mass analyzer according to the seventh aspect. [Explanation of symbols]

[0073] 1...Liquid chromatograph mass spectrometer 10...Liquid chromatograph 20...Mass spectrometer 21…Ionization chamber 211…ESI probe 212... Desolvation tube 22…First intermediate vacuum chamber 221…Ion Guide 222…Skimmer cone 23…Second intermediate vacuum chamber 231…Ion Guide 24…Analysis room 241...quadrupole electrode 242…Collision cell 243...Multipole ion guide 244…Linear ion trap 2441…Front electrode 2442…Back electrode 2443...Rod electrode 2444…Slit 245...Multi-turn time-of-flight mass separator 2451…Ion introduction port 2452…Ion exhaust port 246…Circuit Division 2461...Outer electrode 2462…Inner electrode 247…Ion detector 40...Control and processing section 41...Storage section 51...Mode selection section 52...Reference material determination department 53...Partial mass-to-charge ratio range setting section 54…Measurement execution unit 55…Data Creation Department 56...Normalization coefficient calculation section 57…Data Standardization Division 58…Data Integration Department 6. Input section 7...Display section

Claims

1. dividing the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges based on the mass-to-charge ratio of predetermined reference ions generated from known compounds, such that adjacent partial mass-to-charge ratio ranges overlap; obtaining mass spectrometry data by performing mass spectrometry on the known compounds in each of the plurality of partial mass-to-charge ratio ranges; determining a normalization factor for normalizing the measured intensities of the ions in each of the plurality of partial mass-to-charge ratio ranges based on the measured intensities of the reference ions in the mass spectrometry data acquired in each of the adjacent partial mass-to-charge ratio ranges; obtaining mass spectrometry data by performing mass spectrometry on the measurement target sample in each of the plurality of partial mass-to-charge ratio ranges; normalizing the mass spectrometry data by multiplying the measured intensities of ions in the mass spectrometry data of the sample to be measured acquired in each of the plurality of partial mass-to-charge ratio ranges by a normalization coefficient corresponding to the partial mass-to-charge ratio range; The normalized mass spectrometry data in the plurality of partial mass-to-charge ratio ranges is integrated into one mass spectrometry data. This is a mass spectrometry method.

2. dividing the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges based on the mass-to-charge ratio of predetermined reference ions generated from known compounds, such that adjacent partial mass-to-charge ratio ranges overlap; performing mass spectrometry on the measurement sample to which the known compound has been added in each of the plurality of partial mass-to-charge ratio ranges to obtain mass spectrometry data; normalizing the mass spectrometry data of each of the plurality of partial mass-to-charge ratio ranges so that the measured intensities of the reference ions in the mass spectrometry data acquired in the adjacent partial mass-to-charge ratio ranges are uniform; The normalized mass spectrometry data in the plurality of partial mass-to-charge ratio ranges is integrated into one mass spectrometry data. This is a mass spectrometry method.

3. When integrating the mass spectrometry data, the mass spectrometry data of one partial mass-to-charge ratio range or the average value of the mass spectrometry data of two adjacent partial mass-to-charge ratio ranges is used as the mass spectrometry data corresponding to the overlapping partial mass-to-charge ratio ranges. The mass spectrometry method according to claim 1 or 2,

4. a storage unit that stores a plurality of partial mass-to-charge ratio ranges obtained by dividing the mass-to-charge ratio range of the measurement target so that adjacent partial mass-to-charge ratio ranges overlap with each other at the mass-to-charge ratio of a predetermined reference ion generated from a known compound, and a normalization coefficient for each of the plurality of partial mass-to-charge ratio ranges that is determined based on the measured intensity of the reference ion in mass spectrometry data acquired in each of the adjacent partial mass-to-charge ratio ranges; a measurement execution unit that acquires mass spectrometry data by performing mass spectrometry on a measurement target sample in each of the plurality of partial mass-to-charge ratio ranges; a data normalization unit that normalizes the mass analysis data by multiplying the measured intensities of ions in the mass analysis data of the sample obtained in each of the plurality of partial mass-to-charge ratio ranges by a normalization coefficient corresponding to the partial mass-to-charge ratio range; a data integration unit that integrates the mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization into one mass spectrometry data; A mass spectrometer comprising:

5. moreover, a partial mass-to-charge ratio range setting unit that divides the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges based on the mass-to-charge ratio of a predetermined reference ion generated from a known compound so that adjacent partial mass-to-charge ratio ranges overlap; a second measurement execution unit that acquires mass analysis data by performing mass analysis on the known compounds in each of the plurality of partial mass-to-charge ratio ranges; a normalization coefficient determining unit that determines a normalization coefficient for normalizing the measured intensities of ions in the plurality of partial mass-to-charge ratio ranges based on the measured intensities of the reference ion in the mass analysis data acquired in the adjacent partial mass-to-charge ratio ranges, and stores the plurality of partial mass-to-charge ratio ranges and the normalization coefficient for each of the plurality of partial mass-to-charge ratio ranges in the storage unit; The mass spectrometer of claim 4 , comprising:

6. a partial mass-to-charge ratio range setting unit that divides the mass-to-charge ratio range of the measurement target into a plurality of partial mass-to-charge ratio ranges based on the mass-to-charge ratio of a predetermined reference ion generated from a known compound so that adjacent partial mass-to-charge ratio ranges overlap; a measurement execution unit that performs mass analysis on a measurement sample to which the known compound has been added in each of the plurality of partial mass-to-charge ratio ranges to obtain mass analysis data; a data normalization unit that normalizes the mass analysis data of each of the plurality of partial mass-to-charge ratio ranges so that the measured intensities of the reference ions in the mass analysis data acquired in the adjacent partial mass-to-charge ratio ranges are uniform; a data integration unit that integrates the mass spectrometry data of the plurality of partial mass-to-charge ratio ranges after the normalization into one mass spectrometry data; A mass spectrometer comprising:

7. moreover, A time-of-flight mass separator that makes the ions to be measured fly through a specified flight space The mass spectrometer according to claim 4 , comprising:

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