JP5810983B2 - Compound identification method and compound identification system using mass spectrometry - Google Patents

Description

The present invention relates to a compound identification method and a compound identification system for performing compound identification and structural analysis using information obtained by a mass spectrometer, particularly a mass spectrometer capable of analyzing MS ⁿ (n is an integer of 2 or more).

In mass spectrometry using an ion trap mass spectrometer or the like, a technique called MS / MS analysis (tandem analysis) is known. In general MS / MS (= MS ² ) analysis, first, ions having a specific mass-to-charge ratio m / z are selected as precursor ions from various ions derived from the compound to be analyzed, and the selected ions are identified by CID ( Collision Induced Dissociation) to produce product ions with a small mass-to-charge ratio. The mode of dissociation at this time depends on the structure of the original compound. Therefore, mass spectrometry is performed on product ions generated by dissociation to obtain an MS ² spectrum, and by analyzing this, the target compound is identified and its chemical structure is grasped. Also, if the compound with a large molecular weight or a compound that is difficult to cleave, etc., does not dissociate into ions with a sufficiently small mass-to-charge ratio by one-step CID operation, the CID operation is repeated a plurality of times, and the final product ions are massed. An MS ⁿ analysis to analyze may be performed.

When identifying an unknown compound contained in a sample from data obtained by mass spectrometry (including MS ⁿ analysis), the acquired data is a compound that contains the compound name, composition formula, molecular weight, structural formula, etc. A database search method for collating with a database is widely used (see Patent Document 1). The number of known compounds recorded in the compound database used for such methods has been increasing year by year, and now tens of millions of compounds are recorded. For this reason, when a database search is performed by inputting mass-to-charge ratio information of an ion derived from a target compound obtained by mass spectrometry, an estimated composition formula, or the like, about several hundred candidate compounds are generally extracted. It is extremely difficult to confirm the assignment of peaks on the MS ⁿ spectrum for all of such a large number of candidate compounds. As a result, compound identification is extremely difficult, and even if identification is possible, it takes a very long time.

To deal with such problems, Non-Patent Document 1 discloses that web-based database search using a SciFinder is suitable when the composition formula is available. Non-Patent Document 2 proposes a method of narrowing down compounds using the number of paper citation reports. However, in any of these methods, it is necessary to predict compounds from mass spectrometry results for a wide range of compounds, and it is easy to narrow down candidates to a number that can confirm the assignment of peaks on the MS ⁿ spectrum. is not.

In addition, as a compound identification by a different approach, a database containing the measured values of the mass-to-charge ratio of each peak on the MS ⁿ spectrum derived from the compound is used to determine the homology with the result of mass spectrometry for the unknown compound. A method for predicting the above has also been proposed (see Non-Patent Document 3). However, such a database has not been sufficiently prepared, and the number of recorded compounds is much smaller than that of a normal compound database (14238 as of December 2011). Therefore, there is a high possibility that the compound cannot be identified.

US Patent No. 797402

James L. Little and two others, “Identification of“ Known Unknown ”Utilityizing Accurate Mass Data and Chemical Abstracts Service Databases ( Identification of “Known Unknowns” Utilizing Accurate Mass Data and Chemical Abstracts Service Databases ”, Journal of the American Society for Mass Spectrometry, 2011, 22, p.348-359 Wenta Liao and two others, “Identification of Unknowns in Atmospheric Pressure Ionization Mass Spectrometry Using a Mass to Structure Search・ Engine (Identification of Unknowns in Atmospheric Pressure Ionization Mass Spectrometry Using a Mass to Structure Search Engine) ”, Analytical Chemistry, 2008, 80 (20), p.7765-7777 Horai H. and 34 others, “MassBank: a public repository for sharing mass spectral data for life sciences), Journal of Mass Spectrometry, 2010, 45, pp.703-714

  The present invention has been made to solve the above-mentioned problems, and the object of the present invention is to perform compound identification and structural analysis efficiently and with high accuracy based on data collected by mass spectrometry. It is an object of the present invention to provide a compound identification method and a compound identification system.

The first invention made to solve the above problem is to perform MS ⁿ analysis for dissociating ions derived from a substance to be measured into n-1 (n is an integer of 2 or more) stage, and obtain an MS ⁿ spectrum. A compound identification method for identifying unknown compounds and structural analysis using an acquirable mass spectrometer,
a) a composition formula candidate extraction step for obtaining a composition formula candidate based on the molecular weight of the unknown compound obtained from a mass spectrum obtained by mass spectrometry of the unknown compound;
b) a composition score calculation step for calculating a composition score indicating the coincidence between the theoretical value and the actual measurement value of the molecular weight for each composition formula candidate extracted by the composition formula candidate extraction step;
c) A structure in which a structural formula candidate is extracted by estimating a structural formula corresponding to each composition formula candidate extracted in the composition formula candidate extraction step using a database search for a compound database in which chemical structure information is recorded. An expression candidate extraction step;
d) For each structural formula candidate extracted by the structural formula candidate extraction step, on the spectrum of MS ^m (where m is an integer in the range of 2 to n and an arbitrary number) obtained by mass spectrometry for unknown compounds. A partial structure score calculating step for calculating a partial structure score indicating the coincidence between the mass-to-charge ratio of the peak and the partial structure of the structural formula candidate;
e) a compound estimation step for narrowing down candidate compounds corresponding to unknown compounds based on the composition score of each composition formula candidate and the partial structure score of each structural formula candidate;
It is characterized by having.

A second invention made to solve the above problems is a system for carrying out the compound identification method according to the first invention, wherein ions derived from the substance to be measured are expressed as n-1 (n is A compound identification system that performs identification and structural analysis of unknown compounds using a mass spectrometer capable of acquiring MS ⁿ spectra by performing MS ⁿ analysis to be dissociated in an integer of 2 or more)
a) a composition formula candidate extracting means for obtaining a composition formula candidate based on the molecular weight of the unknown compound obtained from a mass spectrum obtained by mass spectrometry of the unknown compound;
b) a composition score calculation means for calculating a composition score indicating the coincidence between the theoretical value and the actual measurement value of the molecular weight for each composition formula candidate extracted by the composition formula candidate extraction means;
c) A structure in which a structural formula candidate is extracted by estimating a structural formula corresponding to each composition formula candidate extracted by the composition formula candidate extraction means using a database search for a compound database in which chemical structure information is recorded. Expression candidate extraction means;
d) For each structural formula candidate extracted by the structural formula candidate extracting means, on the spectrum of MS ^m (where m is an integer in the range of 2 to n and an arbitrary number) obtained by mass spectrometry for unknown compounds. A partial structure score calculating means for calculating a partial structure score indicating consistency between the peak mass-to-charge ratio and the partial structure of the structural formula candidate;
e) Compound estimating means for narrowing down candidate compounds corresponding to unknown compounds based on the composition score of each composition formula candidate and the partial structure score of each structural formula candidate;
It is characterized by having.

In the compound identification system according to the second invention for carrying out the compound identification method according to the first invention, the composition formula candidate extracting means uses the theoretical mass of various elements based on the precise molecular weight of the unknown compound obtained from the mass spectrum. Thus, a plurality of composition formula candidates are obtained. The higher the accuracy of the actually measured molecular weight, that is, the higher the mass accuracy in mass spectrometry, the narrower the number of composition formula candidates. Therefore, it is preferable to use a mass spectrometer with high mass accuracy. In addition, when estimating the composition formula of an unknown compound, if information on elements included in the unknown compound and information on elements not included are known, it is easy to narrow down composition formula candidates. Therefore, for example, the mass-to-charge ratio difference between the peak on the MS ⁿ spectrum and the peak on the MS ^n-1 spectrum was examined, and the existence of a mass-to-charge ratio difference peculiar to a specific partial structure (for example, hydroxyl group) could be confirmed. In such a case, it may be estimated that the specific partial structure is included.

  The composition score calculation means calculates a composition score for each extracted composition formula candidate according to a predetermined algorithm so as to increase as the coincidence between the theoretical value and the actual measurement value of the molecular weight increases. The structural formula candidate extraction means estimates a structural formula corresponding to each composition formula candidate by performing a database search using each of the composition formula candidates as one of the search conditions. Usually, since a plurality of structural formulas are hit with respect to one composition formula candidate, there are a plurality of structural formula candidates for each composition formula candidate. As the compound database, existing databases provided by various organizations can be used, and databases created by users can also be used.

  Although it is better to use the composition formula candidate as one of the search conditions for the efficiency of the search, after obtaining a large number of structural formula candidates using only the molecular weight as the search condition, the structural formula candidates are associated with the composition formula candidates. It may be determined whether or not it is possible, and structural formula candidates may be obtained by leaving those that can be matched.

For each obtained structural formula candidate, the partial structure score calculation means examines the degree of coincidence between the mass-to-charge ratio of the peak on the MS ^m spectrum obtained by mass spectrometry for the unknown compound and the partial structure of the structural formula candidate. That is, it is examined whether or not the peak on the MS ^m spectrum can be assigned to the partial structure of the structural formula candidate, and the partial structure score is calculated based on the assignment result. Here, when m is one integer in the range of 2 to n, one type of product ion spectrum such as an MS ² spectrum or an MS ³ spectrum is used. When m is a plurality of integers in the range of ² to n, a product ion spectrum including all peaks collected from a plurality of product ion spectra such as MS ² spectrum and MS ³ spectrum, for example, is created. May be used.

The partial structure score preferably reflects the intensity information of the assigned peak. Therefore, the partial structure score calculation means calculates, for example, the sum of the intensities of the peaks that can be assigned among the peaks on the MS ^m spectrum, and uses the ratio of the sum of the intensities of all the peaks on the MS ^m spectrum as the degree of agreement. It can be set as the structure which calculates | requires a score. Further, instead of treating all mass-to-charge ratios fairly, weighting may be performed so that, for example, intensity information of a peak with a large mass-to-charge ratio is relatively emphasized. This is particularly effective when the detection efficiency of ions having a large mass-to-charge ratio is low. Further, weighting may be performed so that intensity information of a peak having a small intensity is relatively neglected. This is effective in suppressing the noise peak particularly in a situation where there is a lot of noise.

  Then, for example, for each structural formula candidate obtained for each composition formula candidate, the compound estimation means calculates a final score based on the composition score of each composition formula candidate and the partial structure score of each structural formula candidate, Narrow down candidate compounds corresponding to unknown compounds according to the score. When obtaining the final score from the composition score and the partial structure score, for example, an average value such as an arithmetic mean or a geometric mean can be used.

  According to the compound identification method and the compound identification system according to the present invention, for a large number of compound candidates obtained from a compound database in which a huge number of compounds are recorded, from mass-to-charge ratio information obtained for the compound to be analyzed Efficiently based on both the composition score indicating the reliability of the estimated composition formula candidate and the partial structure score indicating the reliability of the structure formula candidate extracted by database search for each of the composition formula candidates The compound can be narrowed down. Thereby, since the compound candidates are narrowed down to a relatively small number, it becomes easy for an analyst to finally identify an unknown compound or perform a structural analysis. Moreover, since the database itself used for the database search can use a rich compound, it is possible to reduce the situation where the corresponding compound does not exist in the database and cannot be identified.

1 is a schematic configuration diagram of a compound identification system according to an embodiment of the present invention. The flowchart which shows the compound identification procedure in the compound identification system by a present Example. The schematic diagram for demonstrating the compound identification process according to the flowchart of FIG.

  Hereinafter, an example of a compound identification system for carrying out the compound identification method according to the present invention will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of this compound identification system.

  In the compound identification system of the present embodiment, the mass spectrometer 1 removes an ESI (electrospray ionization) ion source 10 that ionizes a substance in a liquid sample under atmospheric pressure and a solvent mixed in the generated ion stream. A heated capillary tube 11 for introducing ions into a vacuum chamber (not shown), an ion transport optical system 12 for converging the ions to the subsequent stage, a three-dimensional quadrupole ion trap 13, and the ion trap 13 includes a time-of-flight mass analyzer (TOFMS) 14 that mass-separates various ions emitted from 13 according to the time of flight, and a detector 15 that detects ions mass-separated by the TOFMS 14. A normal liquid sample can be introduced into the inlet of the ESI ion source 10, and a liquid sample separated by LC can be continuously introduced by connecting a column outlet of a liquid chromatograph (LC). .

  A detection signal from the detector 15 is input to the processing / control unit 2 and converted into digital data by an A / D converter (not shown), and then predetermined data processing is executed. The processing / control unit 2 includes a data collection processing unit 20, a data storage unit 21, a mass spectrum creation unit 22, a composition estimation unit 23, a composition score calculation unit 24, a structure estimation unit 25, a compound database (DB) 26, a partial structure score. In addition to including functional blocks such as a calculation unit 27 and a compound estimation unit 28, an analysis control unit 31 and a precursor ion automatic selection unit 32 that control each unit of the mass analysis unit 1 are included. The processing / control unit 2 is connected to an input unit 4 and a display unit 5 as user interfaces. Note that most of the functions of the processing / control unit 2 can be realized by a personal computer equipped with dedicated control / processing software.

Although not shown, CID gas can be introduced into the ion trap 13 from the outside, and after selectively capturing ions having a specific mass-to-charge ratio in the ion trap 13, the CID gas is introduced and captured. When ions are resonantly excited by a high-frequency electric field, the ions can collide with CID gas and be cleaved. Further, by repeating the selection of ions and the CID operation, the ions can be cleaved into a plurality of stages to form small fragments. That is, this mass spectrometer is a mass spectrometer capable of MS ⁿ analysis.

  The compound database 26 includes compound names, molecular weights, composition formulas, chemical structural formulas, and the like of various compounds. For example, PubChem (Internet <http: // pubchem) managed by the National Center for Biotechnology Information in the United States. .ncbi.nlm.nih.gov />) can be used. Of course, the compound database 26 is not limited to this. In addition to those provided in general, the compound database 26 may be constructed by the user himself or a combination of an existing database and a user database.

  Next, the mass analysis operation on the target sample and the data collection operation obtained by the analysis performed mainly by the mass analysis unit 1 in the compound identification system of this example will be described.

When an analysis start is instructed by the analyst through the input unit 4, under the control of the analysis control unit 31, the mass analysis unit 1 performs mass analysis (MS ¹ analysis) on a test sample containing an unknown compound at substantially constant time intervals. And MS ² analysis to MS ⁴ analysis are further performed as necessary. The data collection processing unit 20 stores the data obtained by mass spectrometry in the data storage unit 21. More specifically, the mass analyzer 1 first performs MS ¹ analysis of a predetermined mass-to-charge ratio range on the test sample, and the mass spectrum generator 22 calculates the mass (MS ¹ ) spectrum based on the data obtained at this time. Create

The precursor ion automatic selection unit 32 detects a peak that satisfies a predetermined condition on the mass spectrum, and under the control of the analysis control unit 31, the mass analysis unit 1 sets an ion corresponding to this peak as a precursor ion. The MS ² analysis with the CID operation performed is performed following the previous MS ¹ analysis. Since ESI ionization and APCI ionization are so-called soft ionization, ions with protons added or desorbed from molecules tend to be generated most. For this reason, the signal intensity of the molecular ion peak is usually the highest among the ion peaks derived from a certain compound. Therefore, for example, a peak whose signal intensity is equal to or higher than a predetermined threshold and whose signal intensity is maximum may be detected and used as a precursor ion.

The mass spectrum creation unit 22 creates an MS ² spectrum based on the detection signal obtained by the MS ² analysis. Further, the precursor ion automatic selection unit 32 detects a peak that satisfies a predetermined condition on the MS ² spectrum, and under the control of the analysis control unit 31, the mass analysis unit 1 selects ions corresponding to the peak as 2 MS ³ analysis is performed with a two-stage CID operation set to the precursor ion of the stage. Then, the mass spectrum creation unit 22 creates an MS ³ spectrum based on the detection signal obtained by the MS ³ analysis, and detects a peak corresponding to the precursor ion as in the MS ² analysis. Then, the mass spectrometer 1 performs MS ⁴ analysis.

As described above, when the presence of a significant compound is detected in the sample, mass spectrum data and MS ^{2 to} MS ⁴ spectrum data for ions derived from the compound are collected, and all these data are stored in the data storage unit 21. Stored in In this example, the analysis up to MS ⁴ is executed. However, if time permits, an analysis of MS ⁵ or more may be executed. Further, when the molecular weight of the compound is relatively small or the compound is easily dissociated, it is not necessary to perform the MS ⁴ analysis, and up to MS ³ or only MS ² may be executed.

  Next, a characteristic unknown compound identification method performed in a state where mass analysis data for a target sample is stored in the data storage unit 21 by performing the analysis as described above will be described with reference to FIGS. To do. FIG. 2 is a flowchart showing a compound identification procedure, and FIG. 3 is a schematic diagram for explaining a compound identification process according to the flowchart of FIG.

For example, the analyst confirms the total ion chromatogram of the target sample on the screen of the display unit 5, specifies an unknown compound to be identified by the input unit 4, and instructs the identification execution. Then, the mass spectrum creation unit 22 that has received this instruction reads the MS ^{1 to} MS ⁴ spectrum data corresponding to the specified unknown compound from the data storage unit 21, and creates a mass spectrum for each (step S1).

As described above, the molecular ion peak of the target compound that is unknown usually appears clearly on the MS ¹ spectrum. Therefore, the composition estimation unit 23 calculates the measured molecular weight of the target compound from the precise value of the mass to charge ratio of the molecular ion peak of the target compound on the MS ¹ spectrum (step S2). Next, the composition estimation unit 23 uses a known theoretical mass of each element to search for a combination of the element type and the number of elements within a molecular weight range that allows for a predetermined allowable error with respect to the measured molecular weight of the target compound. Thus, a composition formula candidate of the target compound is extracted (step S3). In the example of FIG. 3, three composition formula candidates A, B, and C are extracted by a combination of elements such as carbon C and hydrogen H.

Basically, it is only necessary to use the molecular weight as a clue to estimate the composition formula. However, the composition formula can be estimated easily (that is, it can be done in a short time) by using other information additionally. In some cases, the number of candidates can be reduced. Specifically, for example, if dehydrated ions derived from the target compound are detected on the MS ² spectrum, it can be seen that the target compound includes a hydroxyl group (—OH), and thus includes, for example, one each of oxygen and hydrogen. Such a composition formula can be excluded from the beginning. In addition to this, if ions from which a known characteristic partial structure is desorbed are detected, the composition formula candidates can be limited to elements that necessarily include the partial structure. As a matter of course, it is desirable to take into account the isotopes of each element when estimating the composition formula.

  Next, for each of the plurality of composition formula candidates extracted in step S3, the composition score calculation unit 24 calculates the difference between the theoretical mass value calculated from the theoretical mass of the element included in the composition formula and the measured molecular weight of the target compound. And a composition score indicating the degree of coincidence between the theoretical mass value and the actually measured mass value is calculated based on the difference (step S4). The composition score calculation formula is determined such that the higher the degree of coincidence between the theoretical mass value and the actually measured mass value, that is, the smaller the difference between the two, the larger the composition score. In the example of FIG. 3, composition scores P1, P2, and P3 are obtained for the different composition formula candidates A, B, and C, respectively. This composition score is one index value used in this compound identification.

  Next, the structure estimation unit 25 sets the molecular weight of the target compound (this is common to all composition formula candidates) and the composition formula as search conditions for each of the plurality of composition formula candidates extracted in step S3, and is a compound database. A candidate for a chemical structural formula is extracted by performing a database search for 26 (step S5). In general, since a compound has many isomers, there are a plurality of chemical structural formulas derived by database search even if the molecular weight or composition formula is determined. In the example of FIG. 3, three structural formula candidates A1, A2, and A3 are extracted for the composition formula candidate A, and three structural formula candidates B1, B2, and B3 are extracted for the composition formula candidate B. Three structural formula candidates C1, C2, and C3 are extracted for the candidate C.

Subsequently, the partial structure score calculation unit 27 attempts to assign peaks on the MS ^{2 to} MS ⁴ spectra for each of the chemical structural formula candidates extracted for each of the composition formula candidates in step S5. Based on this, a partial structure score indicating the degree of coincidence between the chemical structural formula and the actually observed product ion is calculated (step S6).

Specifically, for example, the following data processing is executed. First, information (peak mass-to-charge ratio and signal intensity) of peaks observed on each of the MS ^{2 to} MS ⁴ spectra is collected, and an integrated mass spectrum is created by integrating them. For example, when peaks are observed at the same mass-to-charge ratio on the MS ^{2 to} MS ⁴ spectra, the intensities of a plurality of peaks corresponding to the same mass-to-charge ratio are added to obtain the intensity of the peak on the integrated mass spectrum. That's fine. Then, it is examined whether each peak existing on the integrated mass spectrum, that is, a product ion, can be assigned to a partial structure in a given chemical structural formula. Whether or not this assignment is possible may be determined by whether or not the difference between the mass-to-charge ratio of each peak and the mass of the partial structure obtained from the chemical structural formula falls within a predetermined allowable error range.

  If it is determined whether or not all peaks on the integrated mass spectrum are assigned, the assigned peak sum value Iident obtained by adding up the intensities of the assigned peaks is obtained, and on the integrated mass spectrum regardless of whether or not the assignment is possible. The total peak value Itotal obtained by adding the intensities of all the peaks is obtained. Then, the ratio of the sum of the assignable peaks and the sum of all peaks, that is, Iident / Itotal is defined as the degree of coincidence between the chemical structural formula and the actually observed product ion, and this degree of coincidence is multiplied by a predetermined constant. To find the partial structure score. In the example of FIG. 3, partial structure scores Q1, Q2,... Are obtained for the structural formulas A1, A2,. This partial structure score is another index value used in this compound identification.

  As described above, when calculating the partial structure score, the signal intensity of the assigned peak is used, but not all the assigned peaks are treated fairly, but based on the magnitude of the mass-to-charge ratio and the intensity level. Some peaks may be biased by weighting. For example, in general, when comparing ions having a large molecular weight with ions having a small molecular weight, the former has a relatively low passage efficiency of ions from the ion source 10 to the detector 15, and therefore the signal intensity tends to be low on the mass spectrum. is there. Therefore, if all the mass-to-charge peak is treated fairly, the contribution of product ions having a large mass-to-charge ratio is reduced. Therefore, weighting may be performed so that a peak having a larger mass-to-charge ratio is given a greater weight. Further, by performing weighting so that a small weight is given to a peak having a small intensity, an effect of substantially removing a noise peak having a small intensity can be obtained.

  That is, in the processing of steps S1 to S6, composition scores are calculated for each of a plurality of composition formula candidates estimated based on the mass analysis results for the target compound, and further, chemical structural formula candidates estimated for each composition formula candidate. For each, a partial structure score is calculated. In the example of FIG. 3, for example, the composition score of a compound candidate whose chemical structural formula candidate estimated for the composition formula candidate A is A1 is P1, and the partial structure score is Q1.

  The compound estimation unit 28 obtains the composition score obtained in step S4 and the partial structure score obtained in step S6 for one chemical structural formula candidate obtained from a certain composition formula candidate, and the arithmetic average thereof. Or the average value by a geometric mean is calculated and this is made into a total score. Then, the total score is recalculated in the same manner for all chemical structural formula candidates, that is, for the compound candidates (step S7).

  The compound estimation unit 28 narrows down the compound candidates using this total score. That is, for example, a threshold is set in advance for the total score, and compound candidates having a lower total score than the threshold are excluded, and the remaining compound candidates are ranked according to the total score (step S8). Then, the ranked compound candidates are displayed on the screen of the display unit 5 together with the total score (step S9). If there is no significant difference in the overall score, a compound candidate with a high overall score is not necessarily correct. Therefore, the analyst confirms the compound candidate and the total score displayed on the screen of the display unit 5, and identifies the target compound in consideration of other factors. Of course, even if a plurality of compound candidates remain, if there is a candidate that shows an overwhelmingly high value in the overall score, the candidate may be definitely displayed as the target compound.

  As described above, in the compound identification system of this example, the composition formula score given to the estimated composition formula candidate and the partial structure score given to the chemical structure formula candidate estimated corresponding to the composition formula candidate By using both of these, it is possible to efficiently narrow down compound candidates and identify compounds with high accuracy without leakage.

  In the above embodiment, the database search is performed using the composition formula candidate as one of the search conditions in step S5, thereby avoiding hitting a compound candidate that does not correspond to the composition formula candidate. However, in step S5, only chemical structural formula candidates (compound candidates) corresponding to the composition formula candidates can be extracted by another method. For example, when searching the database for the compound database 26, a number of chemical structural formula candidates including those that do not correspond to the composition formula candidates can be obtained by using only the molecular weight of the target compound as a search condition without using the composition formula as a search condition. Is extracted once. After that, it tries to associate the extracted chemical structural formula candidates with the composition formula candidates, and narrows down by excluding the chemical structural formula candidates that do not correspond to any of the composition formula candidates. By such a process, it is possible to finally extract the same chemical structural formula candidates as in the above embodiment.

  Further, the above embodiment is an example of the present invention, and in addition to the above-described various modifications, any modifications, changes, additions, etc. as appropriate within the spirit of the present invention are included in the scope of the claims of the present application. Obviously it will be done.

DESCRIPTION OF SYMBOLS 1 ... Mass spectrometer 10 ... ESI ion source 11 ... Heating capillary tube 12 ... Ion transport optical system 13 ... Ion trap 14 ... TOFMS
DESCRIPTION OF SYMBOLS 15 ... Detector 2 ... Processing / control part 20 ... Data collection processing part 21 ... Data storage part 22 ... Mass spectrum preparation part 23 ... Composition estimation part 24 ... Composition score calculation part 25 ... Structure estimation part 26 ... Compound database 27 ... Part Structure score calculation unit 28 ... Compound estimation unit 31 ... Analysis control unit 32 ... Precursor ion automatic selection unit 4 ... Input unit 5 ... Display unit

Claims (2)

Identification and structure of unknown compounds using a mass spectrometer capable of performing MS ⁿ analysis to dissociate ions derived from the substance to be measured in n-1 (n is an integer of 2 or more) stage to obtain MS ⁿ spectra A compound identification method for performing analysis,
a) a composition formula candidate extraction step for obtaining a composition formula candidate based on the molecular weight of the unknown compound obtained from a mass spectrum obtained by mass spectrometry of the unknown compound;
b) a composition score calculation step for calculating a composition score indicating the coincidence between the theoretical value and the actual measurement value of the molecular weight for each composition formula candidate extracted by the composition formula candidate extraction step;
c) A structure in which a structural formula candidate is extracted by estimating a structural formula corresponding to each composition formula candidate extracted in the composition formula candidate extraction step using a database search for a compound database in which chemical structure information is recorded. An expression candidate extraction step;
d) For each structural formula candidate extracted by the structural formula candidate extraction step, on the spectrum of MS ^m (where m is an integer in the range of 2 to n and an arbitrary number) obtained by mass spectrometry for unknown compounds. A partial structure score calculating step for calculating a partial structure score indicating the coincidence between the mass-to-charge ratio of the peak and the partial structure of the structural formula candidate;
e) a compound estimation step for narrowing down candidate compounds corresponding to unknown compounds based on the composition score of each composition formula candidate and the partial structure score of each structural formula candidate;
The compound identification method characterized by having. Identification and structure of unknown compounds using a mass spectrometer capable of performing MS ⁿ analysis to dissociate ions derived from the substance to be measured in n-1 (n is an integer of 2 or more) stage to obtain MS ⁿ spectra A compound identification system for performing analysis,
a) a composition formula candidate extracting means for obtaining a composition formula candidate based on the molecular weight of the unknown compound obtained from a mass spectrum obtained by mass spectrometry of the unknown compound;
b) a composition score calculation means for calculating a composition score indicating the coincidence between the theoretical value and the actual measurement value of the molecular weight for each composition formula candidate extracted by the composition formula candidate extraction means;
c) A structure in which a structural formula candidate is extracted by estimating a structural formula corresponding to each composition formula candidate extracted by the composition formula candidate extraction means using a database search for a compound database in which chemical structure information is recorded. Expression candidate extraction means;
d) For each structural formula candidate extracted by the structural formula candidate extracting means, on the spectrum of MS ^m (where m is an integer in the range of 2 to n and an arbitrary number) obtained by mass spectrometry for unknown compounds. A partial structure score calculating means for calculating a partial structure score indicating consistency between the peak mass-to-charge ratio and the partial structure of the structural formula candidate;
e) Compound estimating means for narrowing down candidate compounds corresponding to unknown compounds based on the composition score of each composition formula candidate and the partial structure score of each structural formula candidate;
A compound identification system comprising:

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