Mass spectrometry method and mass spectrometer

Abstract

To reduce a change in an integrated mass spectrum pattern even when the number of CE values is different.SOLUTION: A mass spectrometer according to an aspect of the present invention includes a measurement unit (1) that includes a collision cell (17) and mass separation units (20 to 23) for mass spectrometry of product ions, and that can perform MS / MS analysis includes a CES law condition determination unit (321) that determines multiple CE values in a CES method in accordance with a condition including the range of CE values and the number of CE values, and determines n+1 CE values such that n+1 CE values when the number is n+1 (where n is any integer greater than or equal to 3) is obtained by adding one CE value different from n CE values when the number is n to the n CE values when the number is n, an analysis control unit (30) that controls the measurement unit such that the CE continuously changes to the n+1 CE values determined by the CES law condition determination unit and MS / MS analysis under each of the CE values is executed, and a data processing unit (33) that acquires an integrated mass spectrum by integrating the mass spectra under each of the different obtained CE values.SELECTED DRAWING: Figure 1

Description

Technical Field

[0001] The present invention relates to a mass spectrometer capable of MS / MS analysis and a mass spectrometry method in the mass spectrometer.

Background Art

[0002] In order to identify a compound having a large molecular weight or analyze its chemical structure, MS / MS analysis, which is a technique of mass spectrometry, is a useful technique. As a mass spectrometer capable of MS / MS analysis, a triple quadrupole mass spectrometer and a quadrupole-time-of-flight mass spectrometer (hereinafter referred to as "Q-TOF mass spectrometer") are well known. Generally, these mass spectrometers are equipped with a collision cell, and ions introduced into the collision cell having a predetermined energy (collision energy) are collided with a collision gas to cause collision-induced dissociation (CID) to dissociate the ions. Then, a mass spectrum (product ion spectrum) is created by mass-analyzing the product ions generated by the dissociation.

[0003] Since the binding energies of various binding sites in a compound are different for each site, the ease of cleavage of the binding site is also different for each site. Therefore, in the above mass spectrometer, when the collision energy (hereinafter may be abbreviated as "CE") of the ions introduced into the collision cell is changed, even the same ions derived from the same compound have different dissociation modes, and the peak patterns of the obtained product ion spectra are different.

[0004] Generally, for identifying or structurally analyzing a compound having a complex chemical structure, it is convenient to know the masses of various fragments derived from the compound. Therefore, a collision energy spread method (hereinafter referred to as the "CES method"), which repeats product ion scan measurements while changing the CE value in multiple stages for one target compound and creates a mass spectrum in which product ions of various types are observed by integrating the multiple mass spectra thus obtained, has been conventionally known (see Patent Document 1, etc.). The integrated mass spectrum (hereinafter referred to as the "integrated mass spectrum") thus created is a mass spectrum in which peaks derived from various product ions generated by dissociation under different CE values are mixed.

Prior Art Documents

Patent Documents

[0005]

Patent Document 1

Summary of the Invention

Problems to be Solved by the Invention

[0006] In the CES method, it is desirable to integrate mass spectra under various CE values. However, the number of CE values (the number of steps of CE value change) is subject to constraints on analysis conditions such as the number of times of mass spectrum integration and measurement time. In a conventional mass spectrometer, the CE value in the CES method is determined by dividing the range of CE values (lower limit value to upper limit value) directly or indirectly specified as one of the analysis conditions by the number of CE values determined by constraints such as the number of times of spectrum integration and the time assigned to the measurement by the CES method. For example, when the CE value range is 20 to 50 V and the number of CE values is 5, the CE values (V) in the CES method are five steps: 20, 27.5, 35, 42.5, and 50. Also, when the number of CE values is 4 in the same CE value range, the CE values (V) in the CES method are four steps: 20, 30, 40, and 50. Although the unit of the CE value may be eV, it is often shown as the voltage for applying collision energy customarily, so the unit is unified as V here.

[0007] As described above, even if the CE value ranges are the same, if the number of CE values, that is, the analysis conditions, are different, the CE values change greatly, and as a result, the pattern of the integrated mass spectrum may change significantly. Although the integrated mass spectrum is useful for identifying compounds using pattern matching based on a database, if the change in the pattern of the integrated mass spectrum is large when the number of CE values is different, it may hinder the identification of compounds as described above. Also, there is a problem that it is difficult to compare different integrated mass spectra.

[0008] The present invention has been made to solve the above problems, and its main object is to provide a mass spectrometry method and a mass spectrometer capable of avoiding a large change in the pattern of the integrated mass spectrum even when the number of CE values is changed when acquiring the integrated mass spectrum by the CES method.

Means for Solving the Problems

[0009] One aspect of the mass spectrometry method according to the present invention made to solve the above problems includes a measurement unit including a collision cell that dissociates ions and a mass separation unit that mass-analyzes product ions generated by dissociation, and uses a mass spectrometer capable of performing MS / MS analysis, and is a mass spectrometry method that executes a collision energy spread method of obtaining an integrated mass spectrum by integrating the mass spectra obtained while changing the collision energy in multiple stages, A step of determining a plurality of collision energy values in the collision energy spread method corresponding to given conditions including the range of collision energy values and the number of collision energy values, wherein when the number is n + 1 (where n is an arbitrary integer of 3 or more), the n + 1 collision energy values are set to the n collision energy values when the number is n plus one collision energy value different from them. A CES method condition determination step for determining the collision energy values; An analysis execution step of obtaining a mass spectrum for each by controlling the measurement unit to sequentially set the collision energy to the n + 1 collision energy values determined in the CES method condition determination step and execute MS / MS analysis under each collision energy value; It has.

[0010] Also, one aspect of the mass spectrometer according to the present invention made to solve the above problems includes a measurement unit including a collision cell that dissociates ions and a mass separation unit that mass-analyzes product ions generated by dissociation, and is a mass spectrometer capable of performing MS / MS analysis, Determining a plurality of collision energy values in a collision energy spread method corresponding to given conditions including a range of collision energy values and the number of collision energy values, wherein when the number is n + 1 (where n is an arbitrary integer of 3 or more), the n + 1 collision energy values are obtained by adding one collision energy value different from them to the n collision energy values when the number is n. A CES method condition determination unit for determining the n + 1 collision energy values; An analysis control unit that controls the measurement unit to sequentially change the collision energy to the n + 1 collision energy values determined by the CES method condition determination unit and perform MS / MS analysis under each collision energy value; A data processing unit that integrates mass spectra under different collision energy values respectively obtained under the control of the analysis control unit to obtain an integrated mass spectrum; Comprising.

Advantages of the Invention

[0011] According to the above aspect of the mass spectrometry method and the mass spectrometer according to the present invention, when performing the CES method, even when the number of CE values within the range of CE values is different, since there are many common CE values, the difference in the spectrum pattern of the integrated mass spectrum can be suppressed to a small level. Thereby, for example, compound identification by pattern matching or the like using a database of integrated mass spectra can be performed with high accuracy. Also, it becomes easier to compare integrated mass spectra for different samples.

Brief Description of the Drawings

[0012]

Figure 1

Figure 2

Figure 3

Best Mode for Carrying Out the Invention

[0013] Hereinafter, a Q-TOF type mass spectrometer, which is an embodiment of the mass spectrometer according to the present invention, will be described with reference to the accompanying drawings. FIG. 1 is a configuration diagram of a main part of the Q-TOF type mass spectrometer of the present embodiment.

[0014] As shown in FIG. 1, this mass spectrometer includes a measurement unit 1, a control / processing unit 3, an input unit 4, and a display unit 5. The measurement unit 1 includes an ionization chamber 101 in a substantially atmospheric pressure atmosphere and a vacuum chamber 10 internally partitioned into four parts. In the vacuum chamber 10, a first intermediate vacuum chamber 102, a second intermediate vacuum chamber 103, a first high vacuum chamber 104, and a second high vacuum chamber 105 are provided, and each chamber is evacuated by a vacuum pump (turbo molecular pump and rotary pump) (not shown) so that the degree of vacuum increases in this order. That is, this measurement unit 1 has a configuration of a multi-stage differential exhaust system.

[0015] An electrospray ionization (ESI) probe 11 is arranged in the ionization chamber 101, and an eluate is supplied to this ESI probe 11 from the column outlet of a liquid chromatograph (LC) arranged in the previous stage (not shown), for example. The ionization chamber 101 and the first intermediate vacuum chamber 102 communicate with each other through a thin-diameter desolvation tube 12. The first intermediate vacuum chamber 102 and the second intermediate vacuum chamber 103 communicate with each other through an orifice formed at the top of the skimmer 14. In the first intermediate vacuum chamber 102 and the second intermediate vacuum chamber 103, multipole type ion guides 13 and 15 are arranged, respectively.

[0016] Inside the first high-vacuum chamber 104, a quadrupole mass filter 16 and a collision cell 17 with a multipole-type ion guide 18 disposed therein are arranged. Further, a plurality of annular electrodes disposed across the first high-vacuum chamber 104 and the second high-vacuum chamber 105 constitute an ion guide 19. Inside the second high-vacuum chamber 105, an orthogonal acceleration type time-of-flight mass separator including an orthogonal acceleration section 20, a flight tube 22 that forms a flight space 21 therein, and a reflectron 23, and an ion detector 24 are arranged.

[0017] The control and processing unit 3 executes analysis by controlling the measurement unit 1 and performs data processing based on the detection signal obtained by the ion detector 24. The control and processing unit 3 includes, as functional blocks, an analysis control unit 30, an analysis condition setting unit 31, a CES method execution condition determination unit 32, and a data processing unit 33. The CES method execution condition determination unit 32 further includes, as lower-level functional blocks, a CE value number determination unit 320 and a CE value determination unit 321.

[0018] Generally, the entity of the control and processing unit 3 is a personal computer, and by executing a dedicated control and processing software (computer program) installed in the computer on the computer, the above-mentioned respective functional blocks can be embodied. Such a computer program can be stored in a non-transitory computer-readable recording medium such as a CD-ROM, DVD-ROM, memory card, USB memory (dongle), etc. and provided to the user. Alternatively, it can also be provided to the user in the form of data transfer via a communication line such as the Internet. Alternatively, it can also be pre-installed in a computer that is a part of the system in advance when the user purchases the system.

[0019] Next, the operation during product ion scan measurement, which is one of the MS / MS analyses performed in the mass spectrometer of this embodiment, will be schematically described.

[0020] The ESI probe 11 sprays into the ionization chamber 101 while imparting a charge biased towards the introduced liquid sample (e.g., eluate from an LC column). The charged droplets generated by the spraying contact the surrounding high-temperature gas and are refined. In the process where the solvent in the droplets vaporizes, the compounds in the droplets become gaseous ions. The generated ions are sent through the desolvation tube 12 to the first intermediate vacuum chamber 102, and then pass through the ion guide 13, the orifice of the skimmer 14, and the ion guide 15 in sequence, and are introduced into the quadrupole mass filter 16 in the first high-vacuum chamber 104.

[0021] To each of the plurality of rod electrodes constituting the quadrupole mass filter 16, a predetermined voltage obtained by superimposing an RF (high-frequency) voltage on a DC voltage is applied, and ions having a specific mass-to-charge ratio (m / z) corresponding to the voltage are selected as precursor ions. The precursor ions that have passed through the quadrupole mass filter 16 enter the collision cell 17 with collision energy corresponding to the DC potential difference between the quadrupole mass filter 16 and the inlet electrode of the collision cell 17. A collision gas such as Ar is introduced into the collision cell 17, and the precursor ions collide with the collision gas and are dissociated by CID to generate various product ions. The generated product ions exit the collision cell 17 and are transported to the orthogonal acceleration section 20 through the ion guide 19.

[0022] The orthogonal acceleration section 20 simultaneously ejects the incident ions in a direction (Z-axis direction) substantially orthogonal to the incident direction (X-axis direction). The ejected ions fly in the flight space 21 at speeds corresponding to their respective m / z values, and are folded back by the reflection electric field by the reflectron 23 as shown by the two-dot chain line in FIG. 1 and reach the ion detector 24. Various ions that start simultaneously from the orthogonal acceleration section 20 reach the ion detector 24 and are detected in ascending order of their m / z values. The ion detector 24 outputs an ion intensity signal corresponding to the amount of the incident ions as a detection signal to the control and processing unit 3.

[0023] In the control and processing unit 3, the data processing unit 33 digitizes the detection signal and creates a mass spectrum by converting the flight time based on the time when ions are ejected from the orthogonal acceleration unit 20 into an m / z value. The display unit 5 displays the mass spectrum thus created on the screen.

[0024] As already described, when the collision energy in the above MS / MS analysis is changed, the dissociation mode in the collision cell 17 changes, and the types and intensities of mass peaks in the mass spectrum change. The CES method is an analytical method that utilizes this. By acquiring mass spectra at least once each under a plurality of different CE values and integrating the plurality of mass spectra, an integrated mass spectrum reflecting various ions derived from the target component is obtained.

[0025] Next, regarding the characteristic control and processing when implementing the CES method in the mass spectrometer of this embodiment, in addition to FIG. 1, reference will be made to FIG. 2 for explanation. FIG. 2 is a diagram showing an example of the relationship between the number of CE values and the CE values in the mass spectrometer of this embodiment. Further, FIG. 3 is shown for comparison with FIG. 2 and is a diagram showing an example of the relationship between the number of CE values and the CE values in a conventional mass spectrometer.

[0026] Prior to the analysis, the user (operator) inputs the parameter values of the analysis conditions required for the CES method through the input unit 4. The analysis condition setting unit 31 accepts the input of parameter values for each analysis condition. These analysis conditions include the total number of integrations of the mass spectrum and the median value and range of the CE values. Also, the measurement time for the measurement of the CES method and the number of integrations per CE value can be set as one of the analysis conditions. Of course, some of the parameter values of such analysis conditions may be fixed values that cannot be changed by the user.

[0027] The CE value number determination unit 320 determines the number of setting steps of the CE values in the CES method (the number of different CE values, hereinafter referred to as the "number of CE values") based on the total number of integrations of the mass spectrum, the measurement time, the number of integrations per CE value, etc. For example, when the total number of integrations of the mass spectrum is 10 under the constraint of the measurement time and the number of integrations per CE value is 2, the number of CE values is 5. Further, the CE value number determination unit 320 determines the range in which the CE values are changed (hereinafter referred to as the "CE value range") from the median value and the amplitude of the CE values. As shown in FIG. 2, for example, when the median value of the CE values is 35 V and the amplitude is ±15 V, the CE value range is 20 to 50 V.

[0028] When the number of CE values and the CE value range are determined, the CE value determination unit 321 determines a plurality of CE values in the following procedure. Now, assume that the number of CE values is m. First, it is determined whether m satisfies either of the following equations (1) or (2). Here, p is a natural number whose value is determined by equation (1) or (2). m = 2 p +1 …(1) 2 p +1 < m < 2 p+1 +1 …(2) Here, when equation (1) holds, the gain G is obtained by the following equation (3). G = width of CE value range / (m - 1) …(3) The m CE values are obtained by the following equation (4) using the gain G. Here, q is all natural numbers less than or equal to m. [CE] = minimum voltage value of CE value range + G × (q - 1) …(4)

[0029] On the other hand, when equation (2) holds, the excess number H and two gains G1 and G2 are obtained by the following equations (5) to (7). H = m - (2 p +1) …(5) G1 = width of CE value range / 2 p …(6) G2 = width of CE value range / 2 p+1 …(7) The m CE values are obtained by the following equations (8) and (9) using the excess number H, the gains G1, and G2. In the range of q ≤ H × 2: [CE] = the minimum voltage value of the CE value range + G2 × (q - 1) …(8) In the range of q > H × 2: [CE] = the minimum voltage value of the CE value range + G1 × (q - 1 -H ) …(9)

[0030] As an example, as shown in Figure 2, consider the case where the CE value range is 20 - 50V (the width of the CE value range is 30V) and m = 5. In this case, m = 5 = 2 2 + 1, so Equation (1) applies. From Equation (3), G = 30 [V] / 4 = 7.5 is obtained. Therefore, from Equation (4), the five CE values are 20, 27.5, 35, 42.5, 50.

[0031] As another example, as shown in Figure 2, consider the case where the CE value range is 20 - 50V and m = 7. In this case, 2 2 + 1 < m = 7 < 2 3 + 1, so Equation (2) applies. From Equations (5) - (7), H = 7 - (2 2 + 1) = 2, G1 = 30 [V] / 4 = 7.5, G2 = 30 [V] / 8 = 3.75 are obtained. For the CE values, in the range of q ≤ 2 × 2 = 4, from Equation (8), [CE] = 20, 23.75, 27.5, 31.25, 35 are obtained. On the other hand, in the range of q > 4, from Equation (9), [CE] = 42.5, 50 are obtained. Combining these, the m CE values are 20, 23.75, 27.5, 31.25, 35, 42.5, 50.

[0032] Figure 2 shows the relationship between the number of CE values obtained by the above procedure and the CE values. As is clear from Figure 2, one of the features of this method of determining the CE value is that the CE values when the number of CE values is small are always adopted even when the number of CE values is larger. The conventional example shown in Figure 3 is an example in which the CE values are determined by equally dividing the voltage range of the CE values. In this case, the CE values when the number of CE values is small are not necessarily always adopted even when the number of CE values is larger. For example, when the number of CE values is 6, it can be seen that the only commonalities among the CE values when the number of CE values is smaller are the upper limit value and the lower limit value, and there is no other commonality. On the other hand, in an example of the present embodiment shown in Figure 2, it can be seen that all the CE values when the number of CE values is just one less are common.

[0033] Another feature of this method of determining the CE value is that when the value increases by only 1 from a certain number of CE values, only one new CE value is added, which is exactly the intermediate value between two existing adjacent CE values, and the intermediate value is preferentially inserted towards the smaller CE value. The technical significance of these features will be described later.

[0034] When the CE value in the CES method is determined as described above, the information is sent to the analysis control unit 30. The analysis control unit 30 controls the measurement unit 1 so that MS / MS analysis is performed under a plurality of specified CE values. Specifically, by controlling a voltage generation unit (not shown) included in the measurement unit 1, precursor ions are introduced into the collision cell 17 having the specified collision energy.

[0035] The data processing unit 33 receives detection signals obtained by MS / MS analysis under different CE values, and obtains an integrated mass spectrum by integrating the mass spectra corresponding to each MS / MS analysis. In this integrated mass spectrum, mass peaks corresponding to product ions generated by CID under different CE values appear. The data processing unit 33 displays such an integrated mass spectrum on the display unit 5, and calculates, for example, the degree of pattern match between the integrated mass spectrum recorded in a prepared integrated mass spectrum database and the actually measured integrated mass spectrum, and identifies the compound based on the degree of match.

[0036] In the mass spectrometer of this embodiment, since the CE value is determined by the above-described characteristic procedure, there are the following advantages, that is, technical significance. The spectral pattern of the mass spectrum obtained by MS / MS analysis depends on the CE value. Therefore, even when the number of CE values is different, if the commonality of the CE values is high, the spectral patterns of the integrated mass spectra will be similar. Therefore, for example, when performing compound identification using the integrated mass spectrum database as described above, even if the number of CE values when the integrated mass spectrum recorded in the database is obtained is not the same as the number of CE values when the actually measured integrated mass spectrum is obtained, it is generally possible to perform identification determination by pattern matching without problems.

[0037] Also, when comparing the integrated mass spectra obtained for a plurality of samples to determine the identity or structural similarity of compounds, etc., it is not always necessary to align the number of CE values, so there is also an advantage that the flexibility of setting the analysis conditions increases.

[0038] On the one hand, when the CE value is relatively small and when it is large, the influence of the same change amount of the CE value (for example, 1 V) on the difference in the dissociation mode by CID is different. Generally, when the CE value is relatively small, even if the CE value changes by the same amount, the change in the dissociation mode of the ions is large. Therefore, as shown in FIG. 3, when the interval between adjacent CE values is always maintained constant, there is a possibility that sufficient information on product ions for promoting dissociation in the region where the CE value is small cannot be obtained.

[0039] In contrast, in the CE value determination procedure in the present embodiment, as is clear from FIG. 2, since the CE value is preferentially assigned to the region where the CE value is relatively small, in the region where the CE value is small, compared to the region where the CE value is large, the interval between adjacent CE values tends to be narrower. Thereby, compared with the conventional method, information on various product ions can be obtained without leakage and with high sensitivity, and compound identification and structural analysis using an integrated mass spectrum can be advantageously performed.

[0040] In the description of the above embodiment, when determining the CE value in the CE value determination unit 321, the CE value is derived from the set conditions by calculation and determination using a calculation formula. However, a lookup table based on the numerical values obtained from such calculation results may be created and stored. In that case, by inputting the set conditions (for example, the number of CE values and the CE value range) into the lookup table, the resulting CE value can be obtained as an output. Of course, even when obtaining the CE value by calculation and determination using a calculation formula, the above-described procedure is merely an example, and a procedure capable of deriving the same result can be used.

[0041] Further, although the mass spectrometer in the above embodiment is a Q-TOF type mass spectrometer, it is obvious that other types of tandem mass spectrometers capable of MS / MS analysis, such as a triple quadrupole type mass spectrometer, can be used.

[0042] In addition, the above-described embodiments and the above-described modified examples are also examples of the present invention, and it is obvious that appropriate modifications, changes, and additions within the scope of the gist of the present invention are included in the scope of the claims of this application.

[0043] [Various aspects] It is obvious to those skilled in the art that the above-described exemplary embodiments are specific examples of the following aspects.

[0044] (Item 1) One aspect of the mass spectrometry method according to the present invention comprises a measurement unit including a collision cell for dissociating ions and a mass separation unit for mass-analyzing product ions generated by the dissociation, and uses a mass spectrometer capable of performing MS / MS analysis, and executes a collision energy spread method for obtaining an integrated mass spectrum by integrating the mass spectra obtained while changing the collision energy in multiple stages, a step of determining a plurality of collision energy values in the collision energy spread method corresponding to given conditions including the range of the collision energy values and the number of the collision energy values, wherein when the number is n + 1 (where n is an arbitrary integer of 3 or more), the n + 1 collision energy values are determined to be the n collision energy values when the number is n plus one collision energy value different from them, a CES method condition determination step for determining the n + 1 collision energy values; an analysis execution step of obtaining mass spectra respectively by controlling the measurement unit to execute MS / MS analysis under each collision energy value while sequentially setting the collision energy to the n + 1 collision energy values determined in the CES method condition determination step; It has.

[0045] (Item 5) One aspect of the mass spectrometer according to the present invention is a mass spectrometer including a measurement unit including a collision cell for dissociating ions and a mass separation unit for mass-analyzing product ions generated by the dissociation, and capable of performing MS / MS analysis, It determines a plurality of collision energy values in a collision energy spread method corresponding to given conditions including a range of collision energy values and the number of collision energy values. When the number is n + 1 (where n is an arbitrary integer of 3 or more), the n + 1 collision energy values are obtained by adding one collision energy value different from the n collision energy values when the number is n. A CES method condition determination unit that determines the n + 1 collision energy values, An analysis control unit that controls the measurement unit to perform MS / MS analysis under each collision energy value while sequentially changing the collision energy to the n + 1 collision energy values determined by the CES method condition determination unit, A data processing unit that integrates mass spectra under different collision energy values respectively obtained under the control of the analysis control unit to obtain an integrated mass spectrum, Comprising.

[0046] According to the mass spectrometry method described in claim 1 and the mass spectrometer described in claim 5, when performing the CES method, even if the number of CE values is different, there are many common CE values, so the difference in the spectrum pattern of the integrated mass spectrum can be suppressed to a small level. Thereby, for example, compound identification by pattern matching using a database of integrated mass spectra can be performed with high accuracy. Also, it becomes easier to compare integrated mass spectra for different samples.

[0047] (Item 2) In the mass spectrometry method according to Item 1, in the CES method condition determination step, when adding one collision energy value different from the n collision energy values, the one with a larger interval between two adjacent collision energy values along the values is prioritized, and a new collision energy value can be added between the two collision energy values.

[0048] [[ID=**********]] (Item 6) Further, in the mass spectrometer according to Item 5, when the CES method condition determination unit adds one collision energy value different from the n collision energy values, it preferentially selects the one with a large interval between two adjacent collision energy values along the values, and a new collision energy value can be added between the two collision energy values.

[0049] According to the mass spectrometry method described in Item 2 and the mass spectrometer described in Item 6, when determining several or more collision energy values within a predetermined collision energy value range, it is possible to avoid an extremely wide interval between two adjacent collision energy values. Thereby, for product ions generated by promoting dissociation near a specific collision energy value, an integrated mass spectrum that sufficiently reflects the information of the product ions can be obtained.

[0050] (Item 3) In the mass spectrometry method described in Item 2, in the CES method condition determination step, when adding a new collision energy value between the two collision energy values, the intermediate value of the two collision energy values can be added.

[0051] (Item 7) In the mass spectrometer according to Item 6, when the CES method condition determination unit adds a new collision energy value between the two collision energy values, the intermediate value of the two collision energy values can be added.

[0052] According to the mass spectrometry method described in Item 3 and the mass spectrometer described in Item 7, when determining several or more collision energy values within a predetermined collision energy value range, it is possible to avoid an extreme deviation of the collision energy value within that range. Thereby, an integrated mass spectrum that reflects the information of various product ions derived from the target compound in a well-balanced manner can be obtained.

[0053] (Item 4) In the mass spectrometry method according to Item 2 or 3, in the CES method condition determination step, when there are a plurality of cases where the intervals between the two collision energy values are the same, a new collision energy value can be preferentially added to the one with a relatively smaller energy value.

[0054] (Item 8) In the mass spectrometer according to Item 5 or 6, the CES method condition determination unit can preferentially add a new collision energy value to the one with a relatively smaller energy value when there are a plurality of cases where the intervals between the two collision energy values are the same.

[0055] In the mass spectrometry method according to Item 4 and the mass spectrometer according to Item 8, since collision energy values are preferentially assigned to the region where the collision energy value is relatively small, in the region where the collision energy value is small, the interval between adjacent collision energy values tends to be narrower than in the region where the collision energy value is large. Generally, the smaller the collision energy value region, the more sensitive the change in the dissociation mode appears with respect to the change in the collision energy value. For this reason, according to the mass spectrometry method described in Item 4 and the mass spectrometer described in Item 8, information on various product ions can be obtained without omission and with high sensitivity, and compound identification and structure analysis using the integrated mass spectrum can be advantageously performed.

Explanation of Signs

[0056] 1…Measurement unit 10…Vacuum chamber 101…Ionization chamber 102…First intermediate vacuum chamber 103…Second intermediate vacuum chamber 104…First high vacuum chamber 105…Second high vacuum chamber 11…ESI probe 12…Desolvation tube 13, 15, 18, 19…Ion guide 14…Skimmer 16…Quadrupole mass filter 17…Collision cell 20…Orthogonal acceleration section 21…Flight space 22…Flight tube 23…Reflectron 24…Ion detector 3…Control and processing unit 30…Analysis control unit 31…Analysis condition setting unit 32…CES method execution condition determination unit 320…CE value number determination unit 321…CE value determination unit 33…Data processing unit 4…Input unit 5…Display unit

Claims

1. A mass spectrometry method using a mass spectrometer equipped with a measurement unit including a collision cell for dissociating ions and a mass separation unit for mass-analyzing product ions generated by the dissociation, capable of performing MS / MS analysis, and integrating the mass spectra obtained while changing the collision energy in multiple steps to obtain an integrated mass spectrum, comprising: a step of determining a plurality of collision energy values in the collision energy spread method corresponding to given conditions including the range of the collision energy values and the number of the collision energy values, wherein when the number is n + 1 (where n is any integer of 3 or more), the n + 1 collision energy values are determined such that they are obtained by adding one collision energy value different from the n collision energy values when the number is n, which is a CES method condition determination step for determining the n + 1 collision energy values; an analysis execution step of obtaining mass spectra respectively by controlling the measurement unit to perform MS / MS analysis under each collision energy value while sequentially setting the collision energy to the n + 1 collision energy values determined in the CES method condition determination step; A mass spectrometry method having the above steps.

2. In the CES method condition determination step, when adding one collision energy value different from the n collision energy values, priority is given to the one with a larger interval between two adjacent collision energy values along the values, and a new collision energy value is added between the two collision energy values. The mass spectrometry method according to Claim 1.

3. In the CES method condition determination step, when adding a new collision energy value between the two collision energy values, the intermediate value of the two collision energy values is added. The mass spectrometry method according to Claim 2.

4. In the CES method condition determination step, when there are a plurality of cases where the intervals between the two collision energy values are the same, a new collision energy value is preferentially added to the one with a relatively smaller energy value. The mass spectrometry method according to Claim 2 or 3.

5. A mass spectrometer including a measurement unit having a collision cell for dissociating ions and a mass separation unit for mass-analyzing product ions generated by dissociation, and capable of performing MS / MS analysis, which determines a plurality of collision energy values in a collision energy spread method corresponding to given conditions including a range of collision energy values and the number of collision energy values, and when the number is n + 1 (where n is an arbitrary integer of 3 or more), the n + 1 collision energy values are obtained by adding one collision energy value different from the n collision energy values when the number is n, and a CES method condition determination unit that determines the n + 1 collision energy values, an analysis control unit that controls the measurement unit to perform MS / MS analysis under each collision energy value while sequentially changing the collision energy to the n + 1 collision energy values determined by the CES method condition determination unit, a data processing unit that integrates mass spectra under different collision energy values respectively obtained under the control of the analysis control unit to obtain an integrated mass spectrum, A mass spectrometer comprising:

6. The mass spectrometer according to claim 5, wherein when adding one collision energy value different from the n collision energy values, the CES method condition determination unit preferentially adds a new collision energy value between two adjacent collision energy values with a larger interval along the values.

7. The mass spectrometer according to claim 6, wherein when adding a new collision energy value between the two collision energy values, the CES method condition determination unit adds the intermediate value of the two collision energy values.

8. The mass spectrometer according to claim 6 or 7, wherein when there are a plurality of cases where the intervals between the two collision energy values are the same, the CES method condition determination unit preferentially adds a new collision energy value to the one with a relatively smaller energy value.

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