WO2015104844A1 - Procédé de traitement de données de spectrométrie de masse et dispositif de traitement de données de spectrométrie de masse - Google Patents

Procédé de traitement de données de spectrométrie de masse et dispositif de traitement de données de spectrométrie de masse Download PDF

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Publication number
WO2015104844A1
WO2015104844A1 PCT/JP2014/050367 JP2014050367W WO2015104844A1 WO 2015104844 A1 WO2015104844 A1 WO 2015104844A1 JP 2014050367 W JP2014050367 W JP 2014050367W WO 2015104844 A1 WO2015104844 A1 WO 2015104844A1
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mass
analysis
spectrum
compound
ions
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PCT/JP2014/050367
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English (en)
Japanese (ja)
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雄太郎 山村
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株式会社島津製作所
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Priority to PCT/JP2014/050367 priority Critical patent/WO2015104844A1/fr
Publication of WO2015104844A1 publication Critical patent/WO2015104844A1/fr

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    • H—ELECTRICITY
    • H01—ELECTRIC ELEMENTS
    • H01J—ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS
    • H01J49/00—Particle spectrometers or separator tubes
    • H01J49/0027—Methods for using particle spectrometers
    • H01J49/0036—Step by step routines describing the handling of the data generated during a measurement

Definitions

  • the present invention relates to a data processing method and a data processing apparatus for processing mass spectrometry data obtained by a mass spectrometer capable of performing MS n analysis (n is an integer of 2 or more).
  • MS / MS analysis (also referred to as tandem analysis) is one of mass spectrometry techniques used to identify an analysis target compound in a sample.
  • CID collision-induced dissociation
  • the precursor ion does not cleave to a product ion having a small mass-to-charge ratio in one CID, and MS 2 that can be collated with the mass spectrum of the reference compound. Often a spectrum cannot be obtained. In such a case, analysis of MS 3 or higher is performed in which CID is repeated a plurality of times to generate and analyze product ions having a small mass-to-charge ratio.
  • MS n is an integer of 2 or more
  • MS k is an integer of 1 or more and less than n
  • a function (automatic MS n analysis) that automatically selects ions corresponding to a mass peak satisfying a predetermined selection condition (peak intensity is a predetermined value or more) from a plurality of mass peaks as a precursor ion and performs MS k + 1 analysis.
  • a predetermined selection condition peak intensity is a predetermined value or more
  • the ion corresponding to the mass peak is a background ion (such as an ion generated from a mobile phase in a liquid chromatograph or an ion generated from a contaminating component).
  • a background ion such as an ion generated from a mobile phase in a liquid chromatograph or an ion generated from a contaminating component.
  • the problem to be solved by the present invention is obtained by performing MS k analysis (k is an integer of 1 or more and less than n) by a mass spectrometer capable of performing MS n analysis (n is an integer of 2 or more).
  • a mass spectrometry data processing method and apparatus capable of efficiently collecting a mass spectrum of an unknown compound when automatically selecting a precursor ion based on a k spectrum and performing MS k + 1 analysis on the precursor ion. Is to provide.
  • the first aspect of the mass spectrometry data processing method according to the present invention which has been made to solve the above-mentioned problems, is the use of a mass spectrometer capable of performing MS n analysis (n is an integer of 2 or more) of the compound to be analyzed.
  • the mass spectrometry data processing method when an analyst designates a reference compound, ions corresponding to a set of mass-to-charge ratios associated with the reference compound are collectively set as excluded ions. Therefore, not only background ions but also many ions generated from registered compounds can be registered as excluded ions, and mass spectra concerning unknown compounds can be efficiently collected.
  • the predetermined selection condition may be, for example, that the intensity of mass peaks is equal to or greater than a predetermined value, or that a predetermined number of mass peaks are selected in descending order of intensity.
  • the second aspect of the mass spectrometry data processing method according to the present invention which has been made to solve the above-mentioned problems, is the use of a mass spectrometer capable of performing MS n analysis (n is an integer of 2 or more) of the compound to be analyzed.
  • a set of mass-to-charge ratios respectively corresponding to a plurality of mass peaks of the MS k spectrum of the analysis target compound is created in advance for a plurality of reference compounds, and each corresponds to a plurality of mass peaks of the mass spectrum of the reference compound and the reference compound.
  • the reference compound information matched with the mass-to-charge ratio pair to be matched b) determining whether the plurality of mass-to-charge ratio pairs of the analyte compound includes a mass-to-charge ratio pair associated with any of the plurality of reference compounds; c) As a result of the determination, when the plurality of mass-to-charge ratio sets of the analysis target compound does not include any of the plurality of mass-to-charge ratio sets associated with each of the plurality of reference compounds, the MS A precursor ion is selected by extracting a mass peak satisfying a predetermined selection condition from a plurality of mass peaks on the k spectrum.
  • the set of mass to charge ratios respectively corresponding to the plurality of mass peaks of the MS k spectrum of the analysis target compound includes the set of mass to charge ratios corresponding to the reference compound. If the mass spectrum of the reference compound does not exist, a precursor ion is selected and an MS k + 1 spectrum is acquired. Therefore, it is possible to efficiently acquire a mass spectrum related to an unknown compound.
  • the conventionally used mass spectrum matching method takes time because the similarity is determined by comparing the position and intensity of each mass peak of the mass spectrum. Therefore, after acquiring the MS n spectrum, it was necessary to collate with the mass spectrum of the reference compound.
  • the mass spectrum can be collated at high speed, so that the mass spectrum can be collated while proceeding with MS n analysis.
  • the first aspect of the mass spectrometry data processing apparatus has a configuration capable of performing MS n analysis (n is an integer of 2 or more), and MS k analysis (k is 1 or more) of the analysis target compound.
  • a mass spectrometric data processing apparatus that automatically selects a precursor ion based on an MS k spectrum obtained by performing an MS k + 1 analysis on the precursor ion; a) a storage unit that stores reference compound information that is created in advance for a plurality of reference compounds and that associates a reference compound and a set of mass-to-charge ratios respectively corresponding to a plurality of mass peaks of the mass spectrum of the reference compound; b) a display to present the required information to the analyst; c) a reference compound information presentation unit that presents the reference compound information on a screen of the display unit and allows an analyst to select one or more reference compounds; d) an excluded ion setting unit that sets a plurality of mass-to-charge ratios respectively corresponding to the selected one or more reference
  • a second aspect of the mass spectrometry data processing apparatus which has been made to solve the above problems, has a configuration capable of performing MS n analysis (n is an integer of 2 or more), and A mass spectrometry data processing apparatus that automatically selects a precursor ion based on an MS k spectrum obtained by performing MS k analysis (k is an integer of 1 or more and less than n) and performs MS k + 1 analysis on the precursor ion.
  • a storage unit that stores reference compound information that is created in advance for a plurality of reference compounds and that associates a reference compound and a set of mass-to-charge ratios respectively corresponding to a plurality of mass peaks of the mass spectrum of the reference compound; b) a mass-to-charge ratio matching unit that matches a set of mass-to-charge ratios respectively corresponding to a plurality of mass peaks of the MS k spectrum of the analysis target compound with the reference compound information; c) As a result of the collation, when the plurality of mass-to-charge ratio sets of the analysis target compound include a set of mass-to-charge ratios associated with any of the plurality of reference compounds, the MS k spectrum A precursor ion selector that selects a precursor ion by extracting a mass peak satisfying a predetermined selection condition from the plurality of mass peaks; It is characterized by providing.
  • FIG. 1 is a diagram showing a configuration in which the mass spectrometry data processing apparatus of this embodiment is combined with a liquid chromatograph mass spectrometer.
  • the mass spectrometric data processing apparatus of this embodiment controls the operation of a liquid chromatograph mass spectrometer (LC / MS) configured by combining a liquid chromatograph part (not shown) and the mass spectroscope part 1 to control various kinds of samples in a sample. It is a device that performs mass analysis of components and processes data acquired thereby. Specifically, the data processing unit 4 described later corresponds to the mass spectrometry data processing apparatus in the present invention.
  • LC / MS liquid chromatograph mass spectrometer
  • the mass spectrometer 1 removes an ESI (electrospray ionization) ion source 10 that ionizes a substance in a liquid sample whose components are separated by an LC column under atmospheric pressure, and a solvent mixed in the generated ion flow and ion
  • ESI electrospray ionization
  • a heated capillary tube 11 that guides ions into a vacuum chamber (not shown), an ion transport optical system 12 for converging ions to the subsequent stage, a three-dimensional quadrupole ion trap 13, and the ion trap 13
  • a time-of-flight mass analyzer (TOFMS) 14 that mass-separates various ions released from the time of flight, and a detector 15 that detects ions mass-separated by the TOFMS 14.
  • TOFMS time-of-flight mass analyzer
  • the detection signal from the detector 15 is input to the data processing unit 4 and converted into digital data by an A / D converter (not shown), and then predetermined data processing is executed.
  • the data processing unit 4 includes functional blocks of a reference compound information presentation unit 42, an excluded ion setting unit 43, a mass-to-charge ratio matching unit 44, and a precursor ion selection unit 45. Moreover, it is comprised so that a predetermined
  • an input unit 6 and a display unit 7 as a user interface are connected to the data processing unit 4.
  • the function of the data processing unit 4 can be realized by a personal computer equipped with dedicated control / processing software.
  • CID gas can be introduced into the ion trap 13 from the outside in accordance with an instruction from the control unit 5, and after selectively capturing ions having a specific mass-to-charge ratio in the ion trap 13, the CID gas Is introduced, and the captured ions are resonantly excited by a high-frequency electric field (this is referred to as “CID operation”) so that the ions collide with the CID gas and can be cleaved. Furthermore, by repeating the selection of ions and the CID operation, the ions can be cleaved into a plurality of stages, and fragment ions (fragment ions) having a small mass-to-charge ratio can be generated. That is, the mass spectrometer 1 is a mass spectrometer capable of MS n analysis.
  • the storage unit 41 stores a compound database.
  • the compound database includes compound names, molecular weights, composition formulas, chemical structural formulas, and the like of various compounds.
  • PubChem managed by the National Center for Biotechnology Information in the United States can be used.
  • the compound database 26 is not limited to this.
  • the compound database 26 may be constructed by the user himself or a combination of an existing database and a user database.
  • the compound database constructed by the user himself is created based on theoretical information regarding the molecular weight of various compounds. Specifically, compound molecular ions (including those with different valences and those with different polarities), fragment ions generated by cleavage of molecular ions, or adduct ions with water molecules added to them It is information created theoretically.
  • the reference compound information presentation unit 42 When MS n analysis of the sample is indicated by the analyst, before starting the measurement by introducing a sample into LC / MS, the reference compound information presentation unit 42, the reference compounds which are registered in the compound database trout The spectrum is displayed on the display unit 7 and presented to the analyst (step S1, see FIG. 3).
  • the excluded ion setting unit 43 When one or more compounds are selected from the reference compound by the analyst, the excluded ion setting unit 43 collectively selects ions having a mass-to-charge ratio corresponding to each peak of the mass spectrum of the compound as excluded ions.
  • Set Conventionally, an analyst has to input mass-to-charge ratios individually and set exclusion ions one by one, but in this example, when an analyst selects a reference compound, it is associated with the compound. Ions are collectively set as excluded ions.
  • step S2 When step S2 is completed, a signal for instructing the start of measurement is transmitted to the control unit 5, a sample is introduced into the LC / MS under the control of the control unit 5, and mass spectrometry (MS 1 analysis) is performed. (Step S3). Further, as will be described later, MS 2 analysis to MS n analysis are further performed as necessary. Data obtained by these analyzes is stored in the storage unit 41.
  • the mass-to-charge ratio collation unit 44 collates the mass peak of the spectrum with the mass spectrum of the reference compound registered in the compound database. This collation is performed as follows.
  • the mass-to-charge ratio matching unit 44 extracts position information (mass-to-charge ratio) of each peak of the acquired MS 1 spectrum, and generates matching mass spectrum data having a constant value as shown in FIG. . Similarly, position information of each peak is extracted from the mass spectrum of the reference compound (step S4). Then, the matching mass spectrum data obtained from the sample and the matching mass spectrum data created for the reference compound are collated by an AND operation to determine whether or not they match (see FIG. 6). Conventionally, when comparing the mass spectrum obtained for a sample with the mass spectrum of the reference compound, the position information and intensity information of each peak of the mass spectrum are individually verified, and the similarity of the mass spectrum is obtained from the verification results for all peaks. It took a long time because it was determined to be matched / mismatched, and the spectrum could not be verified in parallel with the measurement. However, in the method of this example, the mass spectrum was verified at high speed, and the result was MS n Reflect in measurement.
  • the precursor ion selection unit 45 removes the mass peak corresponding to the previously set excluded ion from the mass peaks of the MS 1 spectrum. A mass peak that satisfies the selection conditions is extracted, and ions corresponding to the mass peak are selected as precursor ions (step S6).
  • the predetermined condition here is, for example, to have an intensity equal to or higher than a preset threshold. Other predetermined conditions may include selecting a preset number of mass peaks in descending order of intensity.
  • an MS 2 spectrum is acquired under the control of the control unit 5 (step S3). Then, by comparing with the mass spectrum of the reference compound in the same procedure as described above, the coincidence / non-coincidence is determined. If the mass spectrum of the coincident reference compound does not exist (NO in step S5), a precursor ion is further selected. Repeat the process of acquiring the MS 3 spectrum. Then, when there is no precursor ion to be selected for the component under analysis, the mass analysis for the component is terminated, and when a new component is introduced from the liquid chromatograph, the mass analysis of the component is started. In the second and subsequent verifications, since a verification mass spectrum related to the reference compound already exists, the step of generating this is omitted, and a new verification mass spectrum is generated only from the mass spectrum obtained for the sample.
  • the MS k spectrum (k is an integer of 1 or more and less than n) obtained by measurement is compared with the mass spectrum of the reference compound to determine match / mismatch, Based on this, a precursor ion for acquiring the MS k + 1 spectrum is selected. Therefore, a mass spectrum related to an unknown compound that is not registered in the compound database can be efficiently acquired.
  • the above-described embodiment is an example, and can be appropriately changed in accordance with the gist of the present invention.
  • the configuration having the characteristics in both the setting of the excluded ion based on the reference compound and the comparison of the mass spectrum of the reference compound has been described, but only one of these may be used.
  • mass spectrometry is similarly performed for MS n analysis using a gas chromatograph mass spectrometer or a mass spectrometer having no chromatograph. Data processing can be performed.
  • the AND operation is used in the comparison of the mass spectrum.
  • the present invention is not limited to this. For example, various methods such as determining the match / mismatch by checking the list of mass-to-charge ratio information are used. Can be used.

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Abstract

La présente invention concerne un procédé de traitement de données de spectrométrie de masse, dans lequel un spectromètre de masse apte à réaliser une analyse MSn (n étant un nombre entier supérieur ou égal à 2) est utilisé pour réaliser une analyse MSn sur un composé d'analyte, et dans lequel des informations de composé de référence qui sont préparées à l'avance pour une pluralité de composés de référence et qui associent chaque composé de référence à un ensemble de rapports masse/charge correspondant respectivement à une pluralité de pics de masse dans le spectre de masse dudit composé de référence sont présentées à l'opérateur, ledit opérateur sélectionne un ou plusieurs composés parmi les composés de référence, et les ions correspondant à l'ensemble ou aux ensembles de rapports masse/charge associés au composé ou aux composés de référence sélectionnés sont tous définis en tant qu'ions exclus. Si l'ensemble de rapports masse/charge correspondant aux pics dans le spectre MSk du composé d'analyte ne comprend pas les ensembles de rapports masse/charge associés aux composés de référence, les ions exclus susmentionnés sont exclus des pics de masse dans le spectre MSk et un ion précurseur est sélectionné.
PCT/JP2014/050367 2014-01-10 2014-01-10 Procédé de traitement de données de spectrométrie de masse et dispositif de traitement de données de spectrométrie de masse WO2015104844A1 (fr)

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Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004071420A (ja) * 2002-08-08 2004-03-04 Hitachi Ltd 質量分析システム、質量分析方法、質量分析装置
JP2012002544A (ja) * 2010-06-14 2012-01-05 Shimadzu Corp クロマトグラフ質量分析装置
JP2012098276A (ja) * 2010-11-03 2012-05-24 Agilent Technologies Inc 質量スペクトルのライブラリをキュレーションするためのシステム及び方法
JP2012225862A (ja) * 2011-04-22 2012-11-15 Shimadzu Corp 質量分析データ処理装置
JP2013224858A (ja) * 2012-04-20 2013-10-31 Shimadzu Corp クロマトグラフタンデム四重極型質量分析装置

Patent Citations (5)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2004071420A (ja) * 2002-08-08 2004-03-04 Hitachi Ltd 質量分析システム、質量分析方法、質量分析装置
JP2012002544A (ja) * 2010-06-14 2012-01-05 Shimadzu Corp クロマトグラフ質量分析装置
JP2012098276A (ja) * 2010-11-03 2012-05-24 Agilent Technologies Inc 質量スペクトルのライブラリをキュレーションするためのシステム及び方法
JP2012225862A (ja) * 2011-04-22 2012-11-15 Shimadzu Corp 質量分析データ処理装置
JP2013224858A (ja) * 2012-04-20 2013-10-31 Shimadzu Corp クロマトグラフタンデム四重極型質量分析装置

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