JP4644560B2 - Mass spectrometry system - Google Patents

Description

  The present invention relates to a separation / analysis system for a sample containing various kinds of components, and more particularly to a liquid chromatograph / mass spectrometry system, analysis method, and apparatus used for analysis of biological substances such as proteins, peptides, sugar chains, and metabolites.

  In recent years, mainly in the fields of biotechnology, drug discovery, diagnosis, and food, proteome analysis, peptideome analysis, and glycome that comprehensively analyze biological substances such as proteins, peptides, sugar chains, and metabolites contained in biological tissues and body fluids Analysis and metabolomic analysis are regarded as important. In these analyses, it is required to accurately identify or quantify a large number of components contained in a sample.

  In the above analysis, a liquid chromatograph / tandem mass spectrometer (LC / MSn) capable of high sensitivity analysis is often used. Liquid chromatograph (LC) separates a liquid sample, and the separated substance is converted into gaseous ions at the interface and introduced into a tandem mass spectrometer (MSn) to obtain a mass spectrum or tandem mass spectrum. Determines the ion mass, the dissociated ion mass, and their ionic strength.

  In a data dependency analysis that is generally used, a specified number of ions are selected as a precursor in descending order of intensity. In addition, a technique for storing information on a predetermined substance, such as ion mass, ion charge number, LC retention time, etc. in an internal database and using it for determining necessity of tandem mass spectrometry or the like [Patent Document 1] and [Patent Document 2]. It is described in. When this internal database is used, the internal database is searched for a predetermined substance in real time and excluded from the precursor ion options in tandem mass spectrometry, so that other components can be subjected to tandem mass spectrometry. Therefore, tandem mass spectrometry technology using an internal database is particularly effective for analyzing trace components.

  Quadrupole mass spectrometer (filter)-Time-of-flight mass spectrometer (Q-TOF) introduces precursor ions selected by the quadrupole filter into a collision cell placed between the quadrupole filter and TOF Then, collision-induced dissociation (CID) is performed, and the dissociated ions can be mass analyzed with TOF. In this Q-TOF, [Patent Document 3] describes a technique for performing tandem mass spectrometry using all ions included in a specific mass range as precursor ions. This is a technique that utilizes a function of transmitting all ions in a specific mass range with a quadrupole filter, and enables tandem mass spectrometry of a plurality of precursor ions. [Patent Document 4] describes a technique for selectively discharging tandem mass spectrometry unnecessary ions in an ion trap mass spectrometer. [Non-Patent Document 3] describes a device that combines a quadrupole filter and a Fourier transform ion cyclotron resonance mass spectrometer. For ions detected in the mass spectrometry spectrum, they were generated by isolation using an ion cyclotron resonance mass spectrometer and dissociation using infrared multiphoton dissociation (IRMPD) using infrared rays or radio frequency (Rf) heating. Analyze dissociated ions. By using the method as described above, it is possible to obtain tandem mass spectrometry spectra of a plurality of precursor ions at the same time.

  In quantitative analysis of separated components by LC, a mass spectrometer (MS) capable of detecting ions with a wide dynamic range is used to analyze changes in ion intensity over time in the obtained mass spectrometry spectrum and tandem mass spectrometry spectrum ( Absolute quantification) is often used. However, when other components are detected at the same time, the ionization efficiency changes, so that accurate quantitative analysis is difficult. In view of this, a technique (for example, [Non-Patent Document 1] and [Non-Patent Document 2]) of analyzing a relative comparison of ionic strength with a standard sample is often used by introducing an isotope labeling method. That is, when the standard sample and the comparative sample are labeled with different stable isotopes, and these mixed samples are analyzed, the same separated components labeled with different isotopes are separated by mass by a number Da by the LC separation components. Is detected. By determining the ionic strength ratio of this pair, a relative quantitative analysis is possible. In the quantitative analysis, depending on the identification accuracy and the quantitative method, the case where the ion intensity in the mass spectrometry spectrum is analyzed and the case where the tandem mass spectrometry spectrum is analyzed are properly used.

JP2004-071420.

JP2005-091344. JP11-154486. JP2005-108578. Nature Biotechnology 23 (2005) 617-621. Nature Biotechnology 17 (1999) 994-999. Analytical Chemistry 73 (2001) 3312-3322.

  In a liquid chromatograph / tandem mass spectrometer (LC / MSn), the time required for detection of separated substances separated by LC with a mass spectrometer (MS) is finite, typically about several tens of seconds. On the other hand, in order to acquire a tandem mass spectrometry spectrum (MS / MS spectrum) or a normal mass analysis spectrum, it takes about 0.1 to several seconds for data acquisition. Therefore, when analyzing a sample in which a large number of contaminant components are mixed, it may be difficult to perform tandem mass spectrometry on all detected separated components.

  On the other hand, in order to perform highly accurate quantitative analysis, it is necessary to obtain a time change with respect to the ionic strength of the separation component. Therefore, it is necessary to acquire about 3 to 10 points of data (mass analysis spectrum or tandem mass analysis spectrum) for one kind of separation component. For this purpose, it is very difficult to perform tandem mass spectrometry for each separated component, particularly when analyzing a sample having a large amount of contaminating components. In addition, when obtaining tandem mass spectrometry spectra of a plurality of precursor ions at the same time, it is necessary to analyze the identification and intensity information of the original precursor ions based on the obtained tandem mass spectrometry spectra.

  In recent years, quantitative analysis of multi-components using high-throughput analysis technology has been attempted mainly in the biomarker search field. In this case, in order to statistically evaluate the analysis results, it is necessary to analyze a large number of samples, and it may be difficult to sufficiently purify and separate the pretreatment. As a result, the characteristics of the analysis of the sample used for analysis are as follows: 1) a very large number of components in the obtained mass spectrometry spectrum, and 2) a very small amount of many kinds of ions that form a broad background in the mass spectrometry spectrum. (Referred to as chemical noise, distinguished from electrical noise). When analyzing such a sample, it is difficult to efficiently obtain a tandem mass spectrometry spectrum of all the detected components even if the internal databases described in [Patent Document 1] and [Patent Document 2] are used.

  Further, as described in [Patent Document 3], when tandem mass spectrometry is performed on all ions belonging to a specific mass range as described in [Patent Document 3], the obtained tandem mass spectrometry spectrum is extremely Complicated and difficult to analyze. In particular, when dissociated ions (fragment ions) derived from different precursor ions that are not sufficiently separated by a mass spectrometer are included, analysis becomes extremely difficult. The inclusion of chemical noise in the precursor ions also makes it difficult to analyze the tandem mass spectrometry spectrum. As described in [Patent Document 4], a similar state is assumed when a plurality of types of precursor ions are subjected to tandem mass spectrometry. That is, for example, when about 100 kinds of separated components are detected at the same time, when these components are simultaneously analyzed by tandem mass spectrometry, the resulting tandem mass spectrometry spectrum becomes complicated, making it difficult to analyze the original precursor ions. there is a possibility. Furthermore, when dissociated ions derived from an unknown substance are included in the tandem mass spectrometry spectrum, it is difficult to obtain a tandem mass spectrometry spectrum of the unknown substance alone and quickly confirm the contents. Actually, it is necessary to perform an analysis once for the data acquisition, which causes a decrease in analysis throughput.

  In addition, when analyzing a sample containing the above-mentioned multiple components, the space charge effect cannot be ignored in the ion trap. That is, when a large amount of ions are introduced into the ion trap, the ion trapping efficiency is reduced, which may adversely affect the quantitative analysis. In order to prevent the space charge effect, it is possible to limit the number of ions taken into the ion trap, but there are cases where it is disadvantageous for high-sensitivity analysis, for example, the precision of quantification is impaired.

The above problem is solved by the following configuration.
(1) Internal database that can register mass information (mass m, number of charges z), LC retention time, and tandem mass spectrometry spectrum information (m / z and intensity of dissociated ions) of the ions to be analyzed When a mass spectrometry spectrum is acquired, an internal database search is performed, and the number of precursor ion groups is determined based on ion intensity and tandem mass spectrometry spectrum information, such as according to the number of candidate precursor ions in tandem mass spectrometry. A high-throughput mass spectrometry system that can classify and perform tandem mass spectrometry for each group in real time and determine the analysis sequence in real time.
(2) The obtained tandem mass spectrometry spectrum is analyzed in real time using an internal database to determine whether dissociated ions derived from unknown substances are included in the tandem mass spectrometry spectrum. When a dissociated ion derived from an unknown substance is contained in a tandem mass spectrometry spectrum, the ion is estimated and a high-throughput mass spectrometry system that can acquire a tandem mass spectrometry spectrum using only that ion as a precursor ion .
(3) Furthermore, it is of course possible to adopt a configuration in which (1) and (2) are combined.
(4) In addition, when there is no need to acquire a tandem mass spectrometry spectrum, it has an internal database that can register mass information (mass m, number of charges z) and LC retention time of ions to be analyzed Once the mass spectrometry spectrum is acquired, the internal database is searched and the precursor ion group is classified into several groups according to the number of analysis ion candidates, and the high-frequency electric field (Rf) is grouped for each group. By performing the isolation used, the space charge effect is reduced and a mass spectrum for quantitative analysis is acquired.

  Examples of the mass spectrometry system include at least one database for storing information on a plurality of substances, an ion source that includes an ion trap unit and ionizes a sample, and mass analysis for ions ionized by the ion source. An input unit for setting conditions for performing dandem mass analysis for each ion group composed of a plurality of ions, and an applied voltage to the ion trap unit based on an input from the input unit And a detection unit that detects an analysis result of the mass analysis unit.

  In addition, as an example of a program related to the execution of a computer for controlling a mass spectrometry system by being read by a computer, a condition for performing dandem mass spectrometry for each ion group composed of a plurality of ions is set as an input unit. A first step that is set via the first step, a second step that obtains information about ions of the dandem mass analysis target by searching the database via the database search means, and a primary mass obtained via the mass analyzer. Based on the analysis result information and the information, a third step of determining the ion group, and on the basis of the result determined in the third step, to the ion trap unit via the power supply control means for dandem mass analysis And causing the computer to execute a fourth step of instructing voltage application.

  According to the present invention, when analyzing a sample in which a very large variety of substances are mixed, it is possible to perform high-throughput quantitative analysis with respect to a substance with an order of magnitude or more compared to the conventional one. Also, unknown substances can be detected efficiently. Furthermore, the correspondence between the fragment ions detected in the tandem mass spectrometry spectrum and the precursor ions can be clarified by using the internal database.

  FIG. 1 shows a system configuration diagram in one embodiment of a mass spectrometry system. This apparatus combines a liquid chromatograph and an ion trap-time-of-flight mass spectrometer. The sample liquid is introduced into a liquid chromatograph pump system, and is introduced into a separation column through a pipe 1. Therefore, many kinds of substances contained in the sample are separated, and the separated substances are sequentially converted into gaseous ions from the column end by a spray ionization method such as an electrospray ionization method. The generated ions are introduced into the vacuum part from the first pore 2 of the mass spectrometer, and are introduced into the ion trap 4 through the ion transport part 3 that generates a constant high-frequency electric field. In the ion trap 4 controlled by the first high-frequency power source, the introduced ions are taken in for a fixed time of about 10 milliseconds. The captured ions are shaped into a thin beam by a collision attenuator 5 composed of a multipole pole controlled by a second high-frequency power source, and introduced into a time-of-flight mass spectrometer 6 in a high vacuum state. The ions accelerated in a pulse manner by the ion accelerating unit 7 are detected by the detector 9 after being subjected to energy convergence by the reflector 8. By accurately measuring the time of flight until ions reach the detector 9, m / z obtained by dividing the mass m of ions by the number of charges z can be determined with high accuracy. When analyzing a sample in which a large variety of substances are mixed, the liquid chromatograph separation column cannot completely separate the components, and the detector 9 often detects a plurality of types of ions. . The detected ion information input to the information processing unit is displayed as a mass spectrum (MS spectrum) on a display unit such as a display.

  Typical internal database registration information is shown in FIG. It is desirable to include information on the name, creation time, and update time of the database. Detected precursor ion (one type) of monoisotopic ion mass m, charge z, m error δm, liquid chromatograph retention time (RT) and RT error δRT, as well as MS / MS spectra The monoisotopic ion mass m, charge z, and ion intensity information (such as relative intensity) of the fragment ion thus registered are registered in the internal database. In addition, when using a mass spectrometer with low mass accuracy, m may not be a monoisotopic ion mass but an average mass. Since the retention time depends on the gradient conditions and the like of the liquid chromatograph, it is convenient that the internal database includes the analysis conditions of the liquid chromatograph. Information on ion dissociation methods (CID, ECD, IRMPD, etc.) in tandem mass spectrometry is also important.

  To create a database, it is necessary to analyze related samples in advance and store ion information in the database. FIG. 18 shows a block diagram of the configuration of the control unit (computer) and its peripheral hardware in the system used for analysis, and FIG. 19 shows the flow of database creation. As shown in FIG. 19, about the result of MS (primary mass spectrometry), based on the ion peak, a search command is sent to the database by the database search means of the control unit, and the corresponding ions are searched. When an unregistered ion is detected, the ion is preferentially selected as a precursor ion, and a normal data-dependent analysis (tandem mass spectrometry) is performed. Then, the analyzed ion information is sequentially registered in the database. Thereby, more ion information can be stored in the database. Furthermore, a large amount of ion information can be registered in the database by repeatedly analyzing the same sample. Based on the above, tandem mass spectrometry using an internal database becomes possible.

  Here, various types of databases can be provided as the internal database. Here, we have an exclusion database (exclusion database) consisting of information on precursor ions excluded from the target of tandem mass spectrometry, and a priority database (inclusion database) consisting of information on precursor ions targeted preferentially. Ion information can be registered separately. For example, when creating and registering a database for blood analysis, ion information obtained using blood as a sample is stored in the inclusion database, and ion information obtained using the epidermis as a sample is stored in the exclusion database. Store. Thereby, when performing mass analysis of blood samples containing contaminants such as proteins derived from the epidermis, flow control of mass spectrometry is performed using both databases, preferentially dandem mass spectrometry of precursor ions derived from blood, and Precursor ions derived from the epidermis can be excluded from tandem mass spectrometry to ensure the execution of blood component analysis.

  Further, each of the exclusion database and the inclusion database can include a plurality of databases. For example, an exclusion database and an inclusion database are created for each analysis condition, sample (blood, urine, etc.) and species (human, mouse, yeast, etc.), and the database is used according to the purpose of mass spectrometry. Can be selected to ensure the optimal analysis execution for the purpose.

  The settings before the start of analysis are shown in FIG. Also, a setting flow is displayed in FIG. FIG. 21 shows a display example on the display unit (input unit) before the start of analysis. In the analysis condition setting part of the display section shown in the figure, input the data file name of the analysis data as appropriate, and select the liquid chromatograph condition setting (LC method) and mass spectrometry condition setting (MS method) prepared in advance, The inclusion database and the exclusion database are selected by the LC method selection unit, the MS method selection unit, the inclusion database selection unit, and the exclusion database selection unit, respectively. Here, the inclusion database is a database of precursor ions to be prioritized for dandem mass spectrometry. Therefore, the MS method selection unit includes options such as “multi-precursor ion selection” (as shown) and “single precursor ion selection”, and the user selects an option according to the purpose of mass spectrometry.

  When the above setting is completed, a screen as shown in FIG. 22 is displayed on the display unit. Here, the final analysis condition is confirmed in the analysis condition confirmation unit of the display unit. When “Multi-precursor ion selection” is selected in the MS method selection section, the multi-precursor selection mode (“Multi-Precursor” in the figure) is displayed on the display section as a condition setting for tandem mass analysis of multiple precursor ions. Ion Selection Mode ")" is displayed. At this time, the number (particularly the maximum number) of precursor ions subjected to tandem mass spectrometry is also displayed. This maximum number is a number according to the calculation processing capability of the processing unit in the multi-precursor ion selection mode. After confirming the conditions, click on Start Analysis to start the analysis. The analysis condition information is input to the information processing unit by input on the display unit, and based on this input, the control unit performs a search command to the database, control to the high frequency power source, and the like. In tandem mass spectrometry using an internal database, the internal database is searched in real time for ions detected in the MS spectrum during sample analysis, and precursor information and MS / MS spectra are selected in the information processing unit. Predictions are made. As shown in FIG. 17, the internal database includes not only information on precursor ions (mass m of monoisotopic peak, number of charges z, liquid chromatograph retention time RT) but also information on dissociated ions (monoisotopic) as ion information. Topic peak mass m, charge number z, relative intensity, dissociation method) are registered. Therefore, given the selected precursor ion and its intensity, the MS / MS spectrum can be predicted by calculating the m / z and relative ion intensity of the dissociated ions. Further, when the MS / MS spectrum is acquired, a comparison with the predicted MS / MS spectrum is performed in the information processing unit, and when a mismatch such as a difference in m / z of dissociated ions is found, the control unit It is possible to send an instruction regarding acquisition of the next MS / MS spectrum to the high frequency power source. It is also possible to collate the predicted spectrum with the detected spectrum in the information processing unit and display the result on the display unit. In this case, as will be described later, unknown ions can be detected. FIG. 23 shows a flow relating to dandem mass spectrometry using an internal database. Information on ions detected by the detector 9 is displayed as a mass spectrum on the display unit, and a database search is performed by the database search means of the control unit. Then, precursor ions for tandem mass spectrometry are determined from the ions hit in the database, and the precursor ions are classified into groups in which tandem analysis is performed at once. Here, by using the database registration information, it is possible to predict a tandem mass spectrum obtained when tandem mass spectrometry of precursor ions classified into the same group is performed.

  FIG. 24 shows a flow of group discrimination from detection of MS results to selection of precursor ions. The information on the ions detected by the detection unit 9 is subjected to a database search by the database search unit of the control unit. Here, in the flow relating to selection of precursor ions, a search in an inclusion database is basically performed. Then, the information processing unit determines an ion hit in the inclusion database as a precursor ion candidate for the dandem MS, and the database search unit searches for the precursor ion information, particularly information on the dandem MS spectrum of the precursor ion. Subsequently, the information processing unit calculates a polymerization spectrum of the tandem MS spectrum hit in the search, and determines whether or not m / z (mass / charge) overlaps among dissociated ions derived from a plurality of precursor ions. If it is expected to overlap, correct the precursor ion grouping. For example, one of the overlapping precursor ions is transferred to the other group. In this way, the selection of grouped precursor ions is performed using the internal database. As a result, a voltage corresponding to each group is applied to the high-frequency power source, and dandem mass spectrometry for each group is executed.

  Returning to the flow of FIG. 23 based on the above, the following description will be given. The power supply control means of the control unit controls the first high-frequency power supply so that only specific precursor ions are taken into the ion trap 4. Then, the precursor ions finally captured by the ion trap 4 are subjected to collision-induced dissociation (CID) with the residual gas by means such as heating by application of a high-frequency electric field or overheating by ion transport to the collision attenuator 5. ) And converted into a plurality of types of dissociated ions (fragment ions). The ion dissociation may be performed in a collision cell 16 installed between the ion trap 4 and the collision attenuator 5 as shown in FIG. These ions are mass-separated by the time-of-flight mass spectrometer 6 and detected by the detector 9. The output signal of the detector 9 is transmitted to the information processing unit, and the detected ion information input to the information processing unit is displayed as a tandem mass spectrum (MS / MS spectrum) on the display unit.

The inclusion database and the exclusion database can be used either alone or both. FIG. 25 shows a flowchart when only the inclusion database is used. At this time, since a database including information on precursor ions to be prioritized for tandem mass spectrometry is used, ions that do not hit the database are not subject to MS / MS (tandem MS). Therefore, it is possible to reliably analyze ions that are preliminarily defined as priority targets for tandem mass spectrometry. FIG. 26 shows a flowchart in the case of using an inclusion database and an exclusion database. At this time, using the exclusion database consisting of information on the precursor ions to be excluded from the target of tandem mass spectrometry, excluding the target excluded ions from the precursor ion candidates, Since the inclusion database consisting of information is used, it is possible to improve the certainty of analysis of ions that are defined as priority targets for tandem mass spectrometry and to increase the efficiency of processing using the inclusion database.
FIG. 2 shows an isolation process when the precursor ion performs one kind of tandem mass spectrometry. The upper diagram of FIG. 2 shows a typical mass spectrum. In addition to the detection of several types of ions, the rise of the baseline due to a large amount of chemical noise is also observed. Such baseline excitement is often seen in biologically extracted samples. When one type of precursor ion is determined, the high-frequency power source can be controlled by changing the Q value of the ion trap so that other ions are not taken in roughly during the ion trapping process of the ion trap. As a result, ions taken into the ion trap become precursor ions, adjacent ions, and chemical noise, as shown in the center diagram. Furthermore, it is possible to isolate only the precursor ions by applying a high-frequency electric field from a high-frequency power source to the ion trap so that ions other than the precursor ions are accurately discharged after the ion uptake is completed. Here, a filtered noise field (FNF) (for example, US Pat. No. 5,206,507) can be used. Then, an MS / MS spectrum of the precursor ion can be obtained by dissociating the isolated precursor ion. Even if other ions are taken in during the ion uptake process, it is possible to isolate only the precursor ions by applying a high-frequency electric field to the ion trap from a high-frequency power source so that ions other than the precursor ions are discharged. It is. However, when a large amount of ions are taken into the ion trap during the uptake process, it may be difficult to accurately isolate only the precursor ions due to the space charge effect.
In the ion trap, a plurality of precursor ions can be isolated simultaneously by the following process. That is, as shown in FIG. 3, precursor ions are selected for each group from the ions detected in the mass spectrum obtained first. In selecting precursor ions, grouping is performed in consideration of ionic strength, prevention of duplication of dissociated ions, and the like from ions hit in the database search. Precursor ions selected for one group are indicated by white circles. The high frequency power supply can be controlled so that other ions are not taken in roughly in the ion trapping process of the plurality of precursor ions. As a result, ions taken into the ion trap become precursor ions, adjacent ions, and chemical noise, as shown in the center diagram. Furthermore, it is possible to isolate only the precursor ions by applying a high-frequency electric field from the high-frequency power source to the ion trap so that ions other than the precursor ions are discharged after the ion uptake is completed. An MS / MS spectrum for a plurality of precursor ions can be obtained by simultaneously dissociating the isolated precursor ions. Even if other ions are taken in during the ion uptake process, it is possible to isolate only the precursor ions by applying a high-frequency electric field to the ion trap from a high-frequency power source so that ions other than the precursor ions are discharged. It is. However, when a large amount of ions are taken into the ion trap during the uptake process, it may be difficult to accurately isolate only the precursor ions due to the space charge effect. Here, prior to analysis, by setting the tandem mass on the display shown in FIG. 21 on the display unit (input unit), the upper limit of the number of precursor ions is set, and the difficulty of isolation due to the space charge effect is reduced. A condition suitable for the information processing capability of the control unit can be set. Especially in the event setting of tandem mass, for the acquired MS / MS spectrum, normal MS / MS spectrum (mode to obtain fragment ion mass spectrum for one kind of precursor ion, single precursor ion selection mode) and multiple precursor ions It is characteristic that it can be set separately from the MS / MS spectrum (multi-precursor ion selection mode). Further, when there are a plurality of internal databases that can be used, it is necessary to make a selection or the like on the input unit while confirming the display contents as shown in FIG. 22 on the display unit.
An example of acquired data in one embodiment of the mass spectrometry system is shown in FIG. In addition to the detection of a very large number of ions, the rise of the baseline due to a large amount of chemical noise is also observed. Such baseline excitement is often seen in biologically extracted samples. In the following, the case of setting to acquire three MS / MS spectra after acquiring one MS spectrum will be described. In the resulting MS spectrum, a very large number of ions are detected and all these ions hit the internal database and should be selected as precursor ions. However, in the above setting, all of these detection ions cannot be individually selected as precursor ions. Therefore, the ions are classified into three groups according to the ion intensity, and ions belonging to the respective groups are simultaneously subjected to tandem mass spectrometry as precursor ions of CID. First, isolation is performed only on relatively strong ions classified in the first group (indicated by white circles in the figure), and other ions and chemical noise components are removed. (In FIG. 4, the isolated mass spectrum is virtual and may not actually be displayed in real time on the display unit.) In this isolation, the ion trap 4 can be used during or after ion capture. A high-frequency electric field having various frequencies and strengths is applied from a high-frequency power source. A number of parameters are used to control this high-frequency power supply. These parameters are calculated by the information processing unit, or optimal values (calculation results) corresponding to various cases are stored in advance, and information processing is performed based on them. This can be determined by performing calculation according to the isolation condition in the section. The isolated precursor ions are simultaneously subjected to a dissociation process such as CID, and an MS / MS spectrum is acquired. When the precursor ion intensity is sufficiently high, a sufficient S / N MS / MS spectrum can be obtained by a single analysis. However, if this is not the case, it is necessary to repeat the analysis several times and obtain an MS / MS spectrum obtained by integrating the analysis results. Optimizing the number of times of integration and the ion uptake time in the ion trap for each group is important for improving the throughput of the entire analysis. Since the ion trapping time in the ion trap is considered to be limited in the amount of ions that can be captured, it is difficult to set the ion trapping time longer than a certain level. Therefore, if the number of integrations is changed, the analysis target ions can be taken in more reliably. In order to perform quantitative analysis, the obtained MS / MS spectrum may display analysis conditions such as ion uptake time and number of integrations, but the ion intensity is displayed as a value normalized to a certain condition. It doesn't matter. Next, MS / MS spectra are obtained by isolating and dissociating only ions with relatively intermediate intensities classified in the second group (indicated by black circles in the figure). To do. Furthermore, isolation is performed only on ions of relatively low intensity classified in the third group (indicated by triangles in the figure), and MS / MS spectra are acquired by dissociating them together. As described above, even when there are many precursor ion candidates, it is possible to suppress a decrease in analysis throughput and perform MS / MS analysis.
The number of integrations in data acquisition is the highest in the third group and the lowest in the first group. The resulting MS / MS spectrum is more complex than the single MS / MS spectrum obtained for a single precursor ion, but it can be analyzed by combining single MS / MS spectral information registered in an internal database. Is possible. That is, dissociated ion information is obtained according to the ion information registered in the database. And the MS / MS spectrum actually obtained by superimposing dissociated ion information (MS / MS spectrum pattern) can be predicted. Therefore, when an unknown substance is included, the presence of dissociated ions that are not in the predicted MS / MS spectrum can be confirmed, and this can be detected quickly. In addition, in the precursor ion selection by internal database search, an unknown substance can be detected, and in that case, a single MS / MS spectrum of only the unknown substance can be acquired (see the description of FIGS. 5 and 6). reference). The display unit displays the MS spectrum and / or the MS / MS spectrum.
With the MS / MS spectrum acquired by the mass spectrometry system as described above, it is possible to acquire MS / MS spectra for a plurality of precursor ions. Therefore, the MS / MS spectrum data is characterized in that it includes a plurality of types of related precursor ion information (mass, etc.). In addition, precursor ion selection is not performed in the mass range, and precursor ion intensity and internal database information are used in selecting a plurality of precursor ions.

The criteria for grouping the first group, the second group, and the third group are that the ion intensity and the m / z of dissociated ions have a difference of a certain value or more (for example, 5 daltons or more), And the number of grouped precursor ions (for example, 20 or less). It is also effective to include only one type of unknown ion in each group. This is because unknown ions can be analyzed with high efficiency unless other unknown ions are included.
Since the precursor ions of the MS / MS spectrum acquired by the mass spectrometry system based on the present invention are basically registered in the internal database, the internal database information can also be used for data analysis after the end of the analysis.
FIG. 5 shows an example of acquired data in one embodiment of the mass spectrometry system. Here, the black inverted triangles indicate ions to be excluded from candidates in the precursor ion selection, and these pieces of ion information are also registered in the internal database (exclusion database) in advance. In the MS spectrum, as in the example of FIG. 4, a large number of ions and chemical noise are detected, and ions classified into a group having high intensity in the precursor selection are displayed as white circles. Using these grouped ions as precursor ions, an MS / MS spectrum is acquired and collated with MS / MS spectrum information registered in an internal database. In the fourth spectrum from the top in the figure, ions that can be collated and verified with respect to the analysis results are indicated by broken lines. Some ions shown by solid lines are inconsistent with MS / MS spectral information registered in the internal database. From this, it can be seen that the grouped precursor ions contained unknown substances not registered in the internal database. Furthermore, the original parent ion can be estimated from the fragment ion information (m, z, ion intensity). In order to confirm the estimation, in this embodiment, a single MS / MS spectrum is acquired only for the estimated precursor ion. If the result is consistent with the fragment ion information indicated by the previous solid line, the information can be newly registered in the internal database. As shown in FIG. 23, in each of the above processes, calculation is performed by the information processing unit, but the calculation time needs to be a short time that does not affect the analysis throughput, and is typically several milliseconds. .

  In precursor ion selection, an internal database search is performed, and as described above, m / z of fragment ions detected in the obtained MS / MS spectrum can be predicted. If it is predicted that dissociated ions derived from different parent ions will overlap in the MS / MS spectrum, reclassify one of the precursor ions into the next group, for example, one precursor ion It is effective to move to a higher group. In this way, database information can be confirmed with high accuracy by the obtained MS / MS spectrum. The actual MS / MS spectrum is verified by the information processing unit using the MS / MS spectrum information registered in the internal database. The number of grouped precursor ions (parent ions) If there is too much, the said verification will become difficult and accuracy will fall. Therefore, in the grouping of precursor ions, an upper limit is set for the types of ions selected, and if this is exceeded, some precursor ion candidates are made stronger in order to reduce the types of ions in the group. It is effective to reclassify to a low group. For example, when the upper limit of the number of candidate precursor ions is set to 20, the number of substances to be analyzed is increased by one digit or more (up to 20 times) as compared with the case where one conventional precursor ion is tandem massed. It is expected. In addition, when multivalent ions such as divalent ions, trivalent ions, and tetravalent ions of the same substance are detected at the same time, it is also useful to include those ions in the same group. The same dissociated ions may be generated, which is advantageous for sensitive analysis.

An example of acquired data in an embodiment of the mass spectrometry system is shown in FIG. In the analysis, an analysis routine is set to acquire three MS / MS spectra for one MS spectrum. As a result of performing an internal database search on the MS spectrum, hit ions are classified into one of three types of precursor ion groups according to the ion intensity, etc., and detection of unknown substances is detected. In this embodiment, first, an MS / MS spectrum of only an unknown substance is acquired, and ion information is registered in an internal database. Next, the precursor ions of the group indicated by white circles are collectively dissociated to obtain an MS / MS spectrum. When the analysis routine is not changed, the ions belonging to the two groups indicated by black circles and triangles are all used as precursor ions, and an MS / MS spectrum is acquired.
In the quantitative analysis, in the method of measuring ionic strength described so far, it is assumed that the ionization efficiency is lowered when a competing substance is present in the ionization process. As a more accurate quantification method, a stable isotope labeling reagent or a relative quantification method of isotopically labeling amino acids (lysine, arginine, etc.) in cultured cells can be used. In this case, the sample to be analyzed and the sample to be compared are individually labeled, the mixed sample is prepared, and the analysis is performed. FIG. 7 (top diagram) shows a typical MS spectrum. Several pairs of ions with different constant mass numbers have been detected. These pairs have almost the same chemical properties but differ only in the isotopes to be labeled. Therefore, the retention time of the liquid chromatograph is detected almost simultaneously. In the relative quantitative analysis, the ion intensity is integrated along the time axis, and the area is obtained. Then, the relative abundance ratio is determined by determining the area ratio. In the analysis, the precursor ions are determined by searching the internal database. In the internal database, information on ion pairs (in the database information shown in FIG. For example, a symbol indicating that the isotope label is added). In determining the precursor ions, even when only one ion is hit in the ion pair registered in the internal database, it is selected as the precursor ion. As a result, even when the intensity ratios of ion pairs are significantly different, quantitative analysis can be performed with high accuracy. FIG. 27 shows a flowchart when the inclusion database and the exclusion database are used, and FIG. 28 shows a flowchart when only the inclusion database is used.
In the example of FIG. 7, an internal database search is performed for ions detected in the MS spectrum. Then, ions excluded from the precursor ion candidates (indicated by inverted triangles) and precursor ion candidates forming a pair (indicated by white circles) are distinguished, and the precursor ion candidates are collectively subjected to tandem mass analysis. An internal database search is performed on the obtained MS / MS spectrum to confirm consistency. In creating an internal database in such an analysis, an analysis is performed in advance using a sample prepared for comparison, and analysis ion information is registered. Next, in consideration of the ion mass that changes when isotope labeling is performed, information on the predicted ion pair is registered in the internal database. Thus, even when only one of the ion pairs is detected, it can be selected as a precursor ion for tandem mass spectrometry.
An example of acquired data in an embodiment of the mass spectrometry system is shown in FIG. As a result of an internal database search for ions detected in the MS spectrum, one type of ion (indicated by an inverted triangle) that is excluded from the precursor ion candidates is detected. All other ions are detected as isotope-labeled pairs, but the ion pairs indicated by arrows are unknown substances that are not registered in the internal database. Guessed. Therefore, first, tandem mass spectrometry using an ion pair of an unknown substance as a precursor ion is performed, and the obtained MS / MS spectrum information is registered in an internal database. Next, the precursor candidate ions are classified into two groups according to ionic strength, and the group [1] (indicated by a white circle) having a relatively high strength (in the ion with the lower ionic strength among the ions forming a pair) Tandem mass spectrometry is performed on all precursor ions. Then, the obtained MS / MS spectrum is acquired and checked against MS / MS spectrum information registered in the internal database. Finally, tandem mass spectrometry is performed on the precursor ions of group [2] (represented by black circles) with relatively low intensity. Then, the obtained MS / MS spectrum is acquired and checked against MS / MS spectrum information registered in the internal database. When confirming MS / MS spectra using internal database information, if m / z of different fragment ions is several Da or less, ion peaks (part of isotope peaks) overlap, which may reduce the analysis accuracy. appear. When the precursor ions are grouped so as to avoid such a situation, the above situation can be avoided. For this reason, in the present embodiment, some precursor ions classified into the group [2] have some intensities that are equivalent to those of the precursor ions classified into the group [1].
It is also possible to carry out quantitative analysis using only the intensity of ions detected in the MS spectrum without acquiring an MS / MS spectrum. In this case, as shown in FIG. 16, performing ion isolation on the ions registered in the internal database analyzes an ion trap that may be subjected to the space charge effect and a sample in which chemical noise cannot be ignored. Is important in case. If the monoisotopic ion mass / charge (m / z) is very close to, for example, about 5 Da, ion loss may occur in isolation. Therefore, in selecting ions to be isolated, it is important to group the ions so that there is some difference in m / z of ions. The obtained MS spectrum is characterized in that the ion intensity may be increased because the space charge effect is reduced as compared with the MS spectrum obtained without performing isolation.
FIG. 9 shows an example of acquired data in one embodiment of the mass spectrometry system. As a result of performing an internal database search for ions detected in the MS spectrum, unlike the case shown in FIG. 6, all the ions are hit by the internal database search. Therefore, the precursor ions are classified into three groups according to the ionic strength, and tandem mass spectrometry is performed on each group.

In FIG. 10, the system block diagram in another one Example of a mass spectrometry system is shown. This device is a device in which a liquid chromatograph and an ion trap-time-of-flight mass spectrometer are combined. In tandem mass spectrometry, not only CID but also electron capture dissociation (ECD) can be used. The sample liquid is introduced into a liquid chromatograph pump system, and is introduced into a separation column through a pipe 1. Therefore, many kinds of substances contained in the sample are separated, and the separated substances are sequentially converted into gaseous ions from the column end by a spray ionization method such as an electrospray ionization method. The generated ions are introduced into the vacuum part from the first pore 2 of the mass spectrometer, and are introduced into the ion trap 4 through the ion transport part 3 that generates a constant high-frequency electric field. In the ion trap 4 controlled by the first high-frequency power source, the introduced ions are taken in for a fixed time of about 10 milliseconds. The captured ions are shaped into a thin beam by a collision attenuator 5 composed of a multipole pole controlled by a second high-frequency power source, and introduced into a time-of-flight mass spectrometer 6 in a high vacuum state. The ions accelerated in a pulse manner by the ion accelerating unit 7 are detected by the detector 9 after being subjected to energy convergence by the reflector 8. By accurately measuring the time of flight until ions reach the detector 9, m / z obtained by dividing the mass m of ions by the number of charges z can be determined with high accuracy. When analyzing a sample in which a large variety of substances are mixed, the liquid chromatograph separation column cannot completely separate the components, and the detector 9 often detects a plurality of types of ions. . The detected ion information input to the information processing unit is displayed as a mass spectrum (MS spectrum) on a display unit such as a display.
Now, the information of the ions detected by the detector 9 is subjected to database search by the database search means of the control unit, and the precursor ions for tandem mass spectrometry are determined based on the ion information hit in the database. And the power supply control means of a control part controls a 1st high frequency power supply so that a specific precursor ion is taken in into the ion trap 4. FIG. The precursor ions finally isolated in the ion trap 4 are subjected to collision-induced dissociation with the residual gas by means such as whether the precursor ions are overheated by applying a high-frequency electric field or heated by ion transport to the collision attenuator 5. CID) and converted into multiple types of dissociated ions (fragment ions). When the precursor ion is a multivalent ion, the precursor ion finally isolated by the ion trap 4 is introduced into the ECD reaction unit 11 by the Q deflector 10. In the ECD reaction unit 11, the introduced multivalent precursor ions are irradiated with low energy electrons, dissociation associated with recombination is realized, and a large number of fragment ions are generated. It is characteristic that when ECD is applied to multivalent ions of peptides and proteins, the main chain is preferentially dissociated. These ions are introduced into the ion acceleration unit 7 from the Q deflector 10. Then, the mass is separated by the time-of-flight mass spectrometer 6 and detected by the detector 9. The output signal of the detector 9 is transmitted to the information processing unit, and the detected ion information input to the information processing unit is displayed as a tandem mass spectrum (MS / MS spectrum) on the display unit. When acquiring a plurality of types of MS / MS spectra, they can be set in the input unit before the analysis is started. Further, when there are a plurality of usable databases, they can be selected by the input unit before the analysis is started. The final analysis setting conditions can be confirmed on the display unit before starting the analysis, and the start of the analysis can be input on the input unit.

In FIG. 11, the system block diagram in another one Example of a mass spectrometry system is shown. This apparatus is an apparatus in which a liquid chromatograph and a linear ion trap mass spectrometer are combined. Similar effects can be obtained by using a three-dimensional ion trap mass spectrometer as shown in FIG. 12 instead of the linear ion trap mass spectrometer.
The sample liquid is introduced into the liquid chromatograph. Therefore, many kinds of substances contained in the sample are separated, and separated substances are sequentially introduced into the ion source from the column end, and converted into gaseous ions by a spray ionization method such as an electrospray ionization method. The generated ions are introduced into the vacuum part from the first pore 2 of the mass spectrometer, and are introduced into the ion trap 4 through the ion transport part 3 that generates a constant high-frequency electric field. In the ion trap 4 controlled by the second high-frequency power source, the introduced ions are taken in for a fixed time of about 10 milliseconds. The taken-in ions are detected by the detector 9 at a timing corresponding to the ion m / z according to the high-frequency electric field applied to the ion trap 4 from the second high-frequency power source. When analyzing a sample in which a large variety of substances are mixed, the liquid chromatograph separation column cannot completely separate the components, and the detector 9 often detects a plurality of types of ions. . The detected ion information input to the information processing unit is displayed as a mass spectrum (MS spectrum) on a display unit such as a display.
Now, the information of the ions detected by the detector 9 is subjected to database search by the database search means of the control unit, and the precursor ions for tandem mass spectrometry are determined based on the ion information hit in the database. Then, the power source control means of the control unit controls the second high frequency power source so that specific precursor ions are taken into the ion trap 4. The precursor ions finally isolated in the ion trap 4 are collided by induced dissociation (CID) with residual gas due to ion overheating of a high-frequency electric field, or infrared multiphoton dissociation (IRMPD) using a carbon dioxide laser or the like. It is converted into a plurality of types of dissociated ions (fragment ions) by means such as an ultraviolet laser (not shown). The output signal of the detector 9 is transmitted to the information processing unit, and the detected ion information input to the information processing unit is displayed as a tandem mass spectrum (MS / MS spectrum) on the display unit. When acquiring a plurality of types of MS / MS spectra, they can be set in the input unit before the analysis is started. Further, when there are a plurality of usable databases, they can be selected by the input unit before the analysis is started. The final analysis setting conditions can be confirmed on the display unit before starting the analysis, and the start of the analysis can be input on the input unit.

FIG. 13 shows a system configuration diagram in still another embodiment of the mass spectrometry system. This apparatus combines a liquid chromatograph and a linear ion trap-Fourier transform ion cyclotron resonance mass spectrometer. In this example, a Fourier transform ion cyclotron resonance mass spectrometer is used instead of the time-of-flight mass spectrometer shown in FIG. Therefore, high resolution and mass accuracy can be easily obtained in ion mass spectrometry.
The sample liquid is introduced into the liquid chromatograph. Therefore, many kinds of substances contained in the sample are separated, and separated substances are sequentially introduced into the ion source from the column end, and converted into gaseous ions by a spray ionization method such as an electrospray ionization method. The generated ions are introduced into the vacuum part from the first pore 2 of the mass spectrometer, and are introduced into the ion trap 4 through the ion transport part 3 that generates a constant high-frequency electric field. In the ion trap 4 controlled by the second high-frequency power source, the introduced ions are taken in for a fixed time of about 10 milliseconds. The taken ions are introduced into the Fourier transform ion cyclotron resonance mass spectrometer 12 in a high vacuum state by a high frequency electric field or an electrostatic field applied to the ion trap 4 from the second high frequency power supply. A magnetic field generated by the magnet 13 is applied to the Fourier transform ion cyclotron resonance mass spectrometer 12, and the ions perform periodic motion according to the m / z. The periodic motion of ions is detected as a change in electric field, and the m / z of ions can be accurately determined from the motion cycle. Instead of the Fourier transform ion cyclotron resonance mass spectrometer 12 that uses a magnetic field, a Fourier transform mass spectrometer (orbitrap) that does not use a magnetic field may be used. When analyzing a sample in which a large variety of substances are mixed, the liquid chromatograph separation column cannot completely separate the components, and the detector 9 often detects a plurality of types of ions. . The detected ion information input to the information processing unit is displayed as a mass spectrum (MS spectrum) on a display unit such as a display.
Now, the information of the ions detected by the detector 9 is subjected to database search by the database search means of the control unit, and the precursor ions for tandem mass spectrometry are determined based on the ion information hit in the database. Then, the power source control means of the control unit controls the second high frequency power source so that specific precursor ions are taken into the ion trap 4. The precursor ions finally isolated by the ion trap 4 are collided by induced dissociation (CID) with residual gas due to ion overheating of a high-frequency electric field, or infrared multiphoton dissociation (IRMPD: diagram) using a carbon dioxide laser. It is converted into a plurality of types of dissociated ions (fragment ions) by means such as (not shown). The output signal of the detector 9 is transmitted to the information processing unit, and the detected ion information input to the information processing unit is displayed as a tandem mass spectrum (MS / MS spectrum) on the display unit. When acquiring a plurality of types of MS / MS spectra, they can be set in the input unit before the analysis is started. Further, when there are a plurality of usable databases, they can be selected by the input unit before the analysis is started. The final analysis setting conditions can be confirmed on the display unit before starting the analysis, and the start of the analysis can be input on the input unit.

In FIG. 14, the system block diagram in another one Example of a mass spectrometry system is shown. This apparatus combines a liquid chromatograph and a tandem ion trap mass spectrometer.
The sample liquid is introduced into the liquid chromatograph. Therefore, many kinds of substances contained in the sample are separated, and separated substances are sequentially introduced into the ion source from the column end, and converted into gaseous ions by a spray ionization method such as an electrospray ionization method. The generated ions are introduced into the vacuum part from the first pore 2 of the mass spectrometer, and are introduced into the ion trap 4 through the ion transport part 3 that generates a constant high-frequency electric field. In the ion trap 4 controlled by the first high-frequency power source, the introduced ions are taken in for a fixed time of about 10 milliseconds. The taken-in ions pass through the collision cell 14 formed of a multipole pole controlled by the second high-frequency power source, and are introduced into another ion trap 15. The ions taken into the ion trap 15 are detected by the detector 9 at a timing corresponding to the ion m / z according to the high-frequency electric field applied to the ion trap 15 from the second high-frequency power source. When analyzing a sample in which a large variety of substances are mixed, the liquid chromatograph separation column cannot completely separate the components, and the detector 9 often detects a plurality of types of ions. . The detected ion information input to the information processing unit is displayed as a mass spectrum (MS spectrum) on a display unit such as a display. When analyzing a sample in which a large variety of substances are mixed, the liquid chromatograph separation column cannot completely separate the components, and the detector 9 often detects a plurality of types of ions. . The detected ion information input to the information processing unit is displayed as a mass spectrum (MS spectrum) on a display unit such as a display.
Now, the information of the ions detected by the detector 9 is subjected to database search by the database search means of the control unit, and the precursor ions for tandem mass spectrometry are determined based on the ion information hit in the database. Then, the power source control means of the control unit is controlled by the second high frequency power source so that the specific precursor ions are taken into the ion trap 4. The precursor ions finally isolated by the ion trap 4 are accelerated and introduced into the collision cell 14 filled with an inert gas such as helium. Then, the precursor ions are dissociated by multiple collisions with the inert gas in the collision cell 14, and the dissociated ions are introduced into another ion trap 15. In accordance with a high-frequency electric field applied to the ion trap 15 from a high-frequency power source, the detector 9 detects at a timing corresponding to the ion m / z. The output signal of the detector 9 is transmitted to the information processing unit, and the detected ion information input to the information processing unit is displayed as a tandem mass spectrum (MS / MS spectrum) on the display unit. When acquiring a plurality of types of MS / MS spectra, they can be set in the input unit before the analysis is started. Further, when there are a plurality of usable databases, they can be selected by the input unit before the analysis is started. The final analysis setting conditions can be confirmed on the display unit before starting the analysis, and the start of the analysis can be input on the input unit.

  Up to now, the online LC / MSn device has been described with emphasis. However, it is effective to have the same function in the offline device. In that case, MALDI (matrix-assisted laser desorption ionization method) using pulsed laser light or the like can be used as the ionization method instead of the spray ionization method. That is, the separated components of the liquid chromatograph (LC) can be sequentially applied to the MALDI plate and subjected to mass spectrometry. When performing such offline analysis, the time limit in the online LC / MSn system is relaxed, so the upper limit on the number of selected precursor ions should be set relatively low in the precursor ion grouping. Can do. And the analysis of the obtained tandem mass spectrum can be simplified. However, if this upper limit is made too low, the analytical throughput will be extremely low. Therefore, the upper limit of the number of precursor ions should be determined in balance with analysis throughput.

US Pat. No. 5,206,507

  The present invention relates to a separation / analysis system for a sample containing various types of components, and more particularly to a liquid chromatograph / mass spectrometry system, analysis method, and apparatus used for analysis of biologically relevant substances such as proteins, peptides, sugar chains, and metabolites.

The system block diagram in one Example of a mass spectrometry system. Isolation process when performing tandem mass spectrometry. Isolation process for multiple precursor ions. The acquisition data example in one Example of a mass spectrometry system. The acquisition data example in one Example of a mass spectrometry system. The acquisition data example in one Example of a mass spectrometry system. An example of typical acquired data of an isotope labeled sample using a mass spectrometry system. The acquisition data example in one Example of a mass spectrometry system. Example of acquired data in one embodiment of mass spectrometry system The system block diagram in another one Example of a mass spectrometry system. The system block diagram in another one Example of a mass spectrometry system. The system block diagram in another one Example of a mass spectrometry system. The system block diagram in another one Example of a mass spectrometry system. The system block diagram in another one Example of a mass spectrometry system. The system block diagram in one Example of a mass spectrometry system. The acquisition data example of the isotope labeled sample using a mass spectrometry system. Example of internal database registration information. The block diagram of a structure with the control part and its peripheral hardware in a system. The figure of the flow in a mass spectrometry system. The figure of the flow in a mass spectrometry system. The example of a display of the display part in a mass spectrometry system. The example of a display of the display part in a mass spectrometry system. The figure of the flow in a mass spectrometry system. The figure of the flow in a mass spectrometry system. The flowchart of the system control in a mass spectrometry system. The flowchart of the system control in a mass spectrometry system. The flowchart of the system control in a mass spectrometry system. The flowchart of the system control in a mass spectrometry system.

Explanation of symbols

1: Tube 1, 2: First pore, 3: Ion transport part, 4: Ion trap, 5: Collision attenuator, 6: Time-of-flight mass spectrometer, 7: Ion accelerator, 8: Reflector, 9: Detector: 10: Q deflector, 11: ECD reaction unit, 12: Fourier transform ion cyclotron resonance mass spectrometer, 13: magnet, 14: collision cell, 15: another ion trap.

Claims (9)

At least one database storing information of a plurality of substances;
An ion source for ionizing a specimen,
A mass spectrometer having an ion trap that performs mass separation of ions ionized by the ion source;
An input for a condition setting for performing data tandem mass spectrometry for each group of ions consisting of a plurality of ions,
A power supply unit in which a voltage applied to the ion trap unit is controlled based on an input from the input unit;
Have a detection unit for detecting the mass separated ions in the mass analyzer,
The ion group that simultaneously performs tandem mass spectrometry is selected based on the ions detected by the detection unit and the information in the database, and the information of the input unit is determined by the output of the detection unit of the selected ion group. A mass spectrometry system characterized by that. The database, the mass spectrometry system according to claim 1, characterized in that it comprises a first database for storing information data tandem mass spectrometry priority target ion. Characterized in that said at least one database, at least one second database storing at least one first database that stores information of data tandem mass spectrometry priority target ions, the information of the data tandem mass spectrometry covered ions The mass spectrometry system according to claim 1. Further comprising a database search unit and the information processing unit, the information processing unit, based on the plurality of information of the substance to be retrieved from the database by the database search unit, to calculate a predicted spectrum of the data tandem mass spectrometry The mass spectrometry system according to claim 1.   The mass spectrometry system according to claim 4, wherein the information processing unit determines the ion group based on the predicted spectrum. The mass spectrometry system according to claim 4, wherein the information processing unit determines the ion group based on ion intensity and m / z information of a primary mass analysis result detected by the detection unit. 2. The database according to claim 1, wherein there are a plurality of the databases, and the input unit includes a database selection unit for selecting the database and a mass analysis condition selection unit for selecting a condition for mass analysis. Mass spectrometry system. Further comprising a display unit for displaying the results of input from the input unit, the display unit, according to claim 1, wherein the displaying the presence or absence of selection of mass spectrometry conditions data tandem mass spectrometry the ions of The mass spectrometric system described in 1. The information of a plurality of materials, mass spectrometry system according to claim 1, characterized in that it comprises ion mass of the material, charge, and the data tandem mass spectrometry.

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