WO2014108992A1 - Dispositif de traitement de données pour chromatographie-spectrométrie de masse - Google Patents

Dispositif de traitement de données pour chromatographie-spectrométrie de masse Download PDF

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Publication number
WO2014108992A1
WO2014108992A1 PCT/JP2013/050062 JP2013050062W WO2014108992A1 WO 2014108992 A1 WO2014108992 A1 WO 2014108992A1 JP 2013050062 W JP2013050062 W JP 2013050062W WO 2014108992 A1 WO2014108992 A1 WO 2014108992A1
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peak
similarity
mass
spectrum
mass spectrum
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PCT/JP2013/050062
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Japanese (ja)
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祐治 勝山
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株式会社島津製作所
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Priority to JP2014556234A priority Critical patent/JP5962775B2/ja
Priority to PCT/JP2013/050062 priority patent/WO2014108992A1/fr
Publication of WO2014108992A1 publication Critical patent/WO2014108992A1/fr

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    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/86—Signal analysis
    • G01N30/8675—Evaluation, i.e. decoding of the signal into analytical information
    • G01N30/8679—Target compound analysis, i.e. whereby a limited number of peaks is analysed
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/72—Mass spectrometers
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/74—Optical detectors
    • G—PHYSICS
    • G01—MEASURING; TESTING
    • G01N—INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES
    • G01N30/00—Investigating or analysing materials by separation into components using adsorption, absorption or similar phenomena or using ion-exchange, e.g. chromatography or field flow fractionation
    • G01N30/02—Column chromatography
    • G01N30/62—Detectors specially adapted therefor
    • G01N30/78—Detectors specially adapted therefor using more than one detector

Definitions

  • the present invention relates to a data processing apparatus for chromatographic mass spectrometry that processes data collected by a chromatographic mass spectrometer such as a liquid chromatograph mass spectrometer (LC / MS) or a gas chromatograph mass spectrometer (GC / MS). .
  • a chromatographic mass spectrometer such as a liquid chromatograph mass spectrometer (LC / MS) or a gas chromatograph mass spectrometer (GC / MS).
  • LC liquid chromatograph
  • GC gas chromatograph
  • the size of the peak on the chromatogram depends on the concentration or amount of the component, if the peak corresponds to a single component, the concentration or content of the corresponding component based on the height or area value of the peak. It is possible to determine the quantity.
  • the peak that appears to be a single shape on the chromatogram is not necessarily due to a single component, and when multiple components that are not sufficiently separated by the column overlap, Often, a component that does not overlap the target component. Therefore, conventionally, a chromatogram peak purity determination process has been performed to determine whether a peak on a chromatogram is due to a single component.
  • Non-Patent Document 1 and Patent Document 1 disclose a technique for determining a peak purity in a chromatogram obtained by a liquid chromatograph using a multichannel detector such as a PDA (Photo Diode Array) detector.
  • a multichannel detector such as a PDA (Photo Diode Array) detector.
  • PDA Photo Diode Array
  • FIG. 2A three-dimensional chromatogram data having three dimensions of time, wavelength, and absorbance is obtained by repeatedly acquiring an absorbance spectrum for the eluate from the column. From the data, an absorbance spectrum at any time point of the peak appearing in the chromatogram can be generated.
  • ⁇ S 1 (a 1 ( ⁇ 1 ), a 1 ( ⁇ 2 ), ..., a 1 ( ⁇ n ))
  • ⁇ S 2 (a 2 ( ⁇ 1 ), a 2 ( ⁇ 2 ), ..., a 2 ( ⁇ n ))
  • a 1 ( ⁇ i ) and a 2 ( ⁇ i ) are absorbances at the wavelength ⁇ i .
  • two vector-expressed absorbance spectra ⁇ S 1 and ⁇ S 2 start from the origin in a two-dimensional space as shown in FIG. It can be expressed as a vector.
  • a vector of the number of wavelengths in a multidimensional space may be considered. If the two absorbance spectra S 1 and S 2 are similar in shape, the two vectors ⁇ S 1 and ⁇ S 2 face the same direction, and the angle formed by both vectors ⁇ S 1 and ⁇ S 2 . ⁇ becomes zero. In general, the smaller the angle ⁇ , the higher the degree of similarity of the curve shapes of the two absorbance spectra S 1 and S 2 .
  • cos ⁇ is calculated and defined as the similarity SI between the two absorbance spectra S 1 and S 2 . That is, the similarity SI between two absorbance spectra S 1 and S 2 can be obtained from the following equation (1). Further, when expression (1) is expressed by each element of vectors ⁇ S 1 and ⁇ S 2 , expression (2) is obtained. It can be said that the shape of the two absorbance spectra S 1 and S 2 agrees better as the value of the similarity SI calculated by the equation (1) or (2) is closer to 1.
  • the absorbance spectrum at the peak top of the target chromatogram peak that is the target of purity determination is S 1 , and an arbitrary peak period from the start point to the end point of the target peak is set.
  • the absorbance spectrum obtained by the time and S 2 calculates each similarity SI at each time point.
  • the chromatogram peak area is color-coded according to the similarity SI value so that the change of the calculated similarity SI value with time can be seen at a glance.
  • the similarity SI is the highest near the peak top and gradually decreases as the distance from the peak top increases, and the shape is generally symmetrical with respect to the central axis of the peak. Become.
  • the operator can determine that there is a high possibility that impurities are included in the time range in the vicinity thereof.
  • the FIA method is a method in which a predetermined amount of sample is injected into a mobile phase fed at a constant flow rate using a liquid chromatograph injector or the like, and the sample is introduced into a detector by being placed on the flow of the mobile phase. Yes, as with the eluate from the column outlet, the concentration of the target component changes in an approximately mountain shape over time.
  • the data obtained when a sample introduced by the FIA method is detected by a multichannel detector is also three-dimensional data having three dimensions of time, wavelength, and absorbance, and is a liquid chromatograph as described above.
  • the “chromatograph mass spectrometer” as used in this specification includes not only a chromatograph column but also an apparatus for introducing a sample into the mass spectrometer by the FIA method.
  • the present invention has been made in order to solve the above-mentioned problems.
  • the main purpose of the present invention is that the peak of another component having a shape similar to that of the target compound in the absorbance spectrum is present relative to the chromatogram peak of the target compound. It is an object of the present invention to provide a data processing apparatus for chromatographic mass spectrometry capable of performing a highly reliable peak purity determination, which can identify the overlap of impurities even when they overlap.
  • Another object of the present invention is to provide a data processing apparatus for chromatographic mass spectrometry that can estimate what a component is when it is found that another component overlaps the chromatogram peak of the target compound. Is to provide.
  • the first aspect of the present invention provides data for processing data collected by a chromatograph mass spectrometer combining a chromatograph having a multichannel detector and a mass spectrometer.
  • a processing device comprising: a) First to detect a peak derived from a target compound in a chromatogram created based on the first three-dimensional chromatogram data collected by the multi-channel detector and having dimensions of time, wavelength, and absorbance.
  • a peak detector b) Detecting a peak derived from the target compound in a chromatogram created based on the second three-dimensional chromatogram data collected by the mass spectrometer and having dimensions of time, mass-to-charge ratio, and signal intensity.
  • a second peak detector Regarding the peak derived from the target compound detected by the first peak detector, the absorbance spectrum to be evaluated at each other time point during the period in which the peak appears, and the reference absorbance spectrum at the peak top of the peak or the evaluation object A first similarity calculator that calculates the similarity of the pattern with the reference absorbance spectrum at a time point away from the absorbance spectrum for a predetermined period; d) For the peak derived from the target compound detected by the second peak detector, the evaluation target mass spectrum at each point in time during which the peak appears, and the reference mass spectrum at the peak top of the peak or the evaluation target mass A second similarity calculator for calculating the similarity of the pattern with the reference mass spectrum at a time point away from the spectrum for a predetermined period; e) A graph in which the similarity at each time point calculated by the first similarity calculation unit is plotted on the time axis, and a similarity in each time point calculated by the second similarity calculation unit is plotted on the time axis.
  • a similarity evaluation information presentation unit that
  • the second aspect of the present invention processes data collected by a chromatograph mass spectrometer that is a combination of a chromatograph having a multi-channel detector and a mass spectrometer.
  • a data processing device a) First to detect a peak derived from a target compound in a chromatogram created based on the first three-dimensional chromatogram data collected by the multi-channel detector and having dimensions of time, wavelength, and absorbance.
  • a peak detector b) Detecting a peak derived from the target compound in a chromatogram created based on the second three-dimensional chromatogram data collected by the mass spectrometer and having dimensions of time, mass-to-charge ratio, and signal intensity.
  • a second peak detector Regarding the peak derived from the target compound detected by the first peak detector, the absorbance spectrum to be evaluated at each other time point during the period in which the peak appears, and the reference absorbance spectrum at the peak top of the peak or the evaluation object A first similarity calculator that calculates the similarity of the pattern with the reference absorbance spectrum at a time point away from the absorbance spectrum for a predetermined period; d) For the peak derived from the target compound detected by the second peak detector, the evaluation target mass spectrum at each point in time during which the peak appears, and the reference mass spectrum at the peak top of the peak or the evaluation target mass A second similarity calculator for calculating the similarity of the pattern with the reference mass spectrum at a time point away from the spectrum for a predetermined period; e) A graph in which the similarity at each time point calculated by the first similarity calculation unit is plotted on the time axis, and a similarity in each time point calculated by the second similarity calculation unit is plotted on the time axis. A determination unit for determining whether or
  • the “chromatograph” may be either a liquid chromatograph or a gas chromatograph.
  • “multi-channel detectors” generally have a combination of a spectroscope and a photodiode array (PDA) detector that detects wavelength-dispersed light at the same time. As long as it is broad (slow change), UV-visible spectrophotometer, infrared spectrophotometer, near-infrared spectrophotometer, fluorescence spectrophotometer with wavelength scanning to obtain absorbance spectrum , Etc.
  • PDA photodiode array
  • the “chromatograph mass spectrometer” separates components by the FIA method using a liquid chromatograph injector or the like instead of introducing a sample through a column for separating components in a chromatograph into the mass spectrometer. A sample that is not present may be introduced into the mass spectrometer.
  • the “chromatogram created based on the first three-dimensional chromatogram data” is usually a mass chromatogram (also referred to as “extracted ion chromatogram”) at a specific mass-to-charge ratio.
  • a total ion chromatogram may be used.
  • the similarity of the absorbance spectrum pattern conventionally used for determining the purity of the peak derived from the target compound appearing in the chromatogram is used in addition to the property.
  • the second peak detector when SIM (Selection Ion Monitoring) measurement for a plurality of mass-to-charge ratios or scan measurement for a predetermined mass-to-charge ratio range is executed in a mass spectrometer, three-dimensional chromatogram data having dimensions of time, mass-to-charge ratio, and signal intensity. Therefore, the second peak detector generates a mass chromatogram based on the three-dimensional chromatogram data, for example, in the mass-to-charge ratio corresponding to the target compound (typically, the quantitative ion characterizing the target compound), A peak near the retention time of the target compound is detected on the chromatogram.
  • SIM Selection Ion Monitoring
  • the second similarity calculation unit calculates a mass spectrum to be evaluated at a certain point in time during which the peak appears, and a reference at a point apart from the mass spectrum to be evaluated for a predetermined period.
  • the process of calculating the similarity of the pattern with the mass spectrum (or the reference mass spectrum at the peak top) is repeatedly executed for all the time points in the peak period or at least a part of the time points.
  • the operator when using a mass spectrum at a time point away from the evaluation target mass spectrum for a predetermined period as the reference mass spectrum, it is preferable that the operator can appropriately set the value of the predetermined period. This is because it is preferable that the predetermined period can be adjusted according to the temporal spread of the impurities overlapping the peak derived from the target compound.
  • the similarity evaluation information presentation unit plots the similarity at each time point calculated based on the absorbance spectrum on the time axis, Create a graph plotting the similarity at each time point calculated based on the mass spectrum on the time axis, and compare the graphs of these two similarities on the display screen, for example, overlaying on the same time axis indicate.
  • the determination unit executes a determination process in place of the operator's determination as described above. Specifically, for example, when the slope of the curve indicating the temporal change in similarity or the rate of change is calculated, and there is a drop in which the degree of similarity reduction based on such calculation results is greater than or equal to a threshold value, It is determined that there is an overlap.
  • a determination unit that performs such automatic determination and a similarity evaluation information presentation unit that displays a graph relating to two similarities may be provided.
  • the mass spectrum near the peak top of the negative peak where the similarity falls, and before the falling of the peak near the negative peak or after the rising A subtraction processing unit for obtaining a difference mass spectrum from the mass spectrum at the time point;
  • the peak intensity on the mass spectrum depends on the concentration (amount) of the contained component at each time point, when calculating the differential mass spectrum, the difference in the concentration of the target compound in the two mass spectra may be corrected.
  • the difference mass spectrum is an impurity-derived mass spectrum
  • the impurity estimation unit qualifies the impurity by, for example, checking the pattern of the difference mass spectrum with the mass spectrum pattern in the compound qualitative database.
  • the information on the retention time can also be used when qualifying the impurity. This not only reveals that the impurities are overlapping, but also makes it possible to know the components.
  • the first similarity calculation unit calculates the similarity. It is preferable to execute a process of removing background noise of each mass spectrum before.
  • the first similarity calculation unit calculates a peak below a predetermined threshold for each mass spectrum before calculating the similarity. It is advisable to execute the removal process.
  • the mass spectrum pattern is simplified while retaining the characteristics of the contained compounds.
  • the calculation process is simplified and the time required for this can be reduced.
  • the accuracy of similarity calculation itself can be improved, and the accuracy of peak purity determination can be improved.
  • the data processing apparatus for chromatographic mass spectrometry it is possible to determine the purity of the peak appearing in the chromatogram with higher reliability than before. In particular, since impurities that cannot be detected by conventional peak purity determination methods can be detected, the accuracy of peak purity determination is greatly improved. Further, according to the preferred configuration in which the subtraction processing unit and the impurity estimation unit are added in the chromatograph mass spectrometry data processing device according to the present invention, it is possible to simply determine whether or not the impurity is overlapped with the peak derived from the target compound. In addition to being able to do so, it becomes possible to know what the impurities are.
  • the block diagram of the principal part of the liquid chromatograph mass spectrometer (LC / MS) provided with the data processor for chromatograph mass spectrometry which is one Example of this invention. It is a conceptual diagram which shows an example of the three-dimensional chromatogram data obtained by LC / MS of a present Example, (a) is the data obtained with a PDA detector, (b) is the data obtained with a mass spectrometer.
  • Explanatory drawing of the mass spectrum similarity calculation method at the time of performing peak purity determination in LC / MS of a present Example The figure which shows the example of a display of the similarity graph for peak purity determination in LC / MS of a present Example.
  • FIG. 1 is a configuration diagram of a main part of the LC / MS of this embodiment
  • FIG. 2 is a conceptual diagram showing an example of three-dimensional chromatogram data obtained by the LC / MS of this embodiment.
  • the LC unit 1 includes a mobile phase container 11, a liquid feed pump 12, a sample injection unit 13, a column 14, and a PDA detector 15.
  • the liquid feed pump 12 sucks the mobile phase from the mobile phase container 11 and sends it to the sample injection unit 13 at a constant flow rate.
  • the sample injection unit 13 injects a sample into the mobile phase at a predetermined timing. The injected sample rides on the flow of the mobile phase and is sent to the column 14. While passing through the column 14, each component in the sample is separated and eluted in the time direction.
  • the PDA detector 15 which is a kind of multi-channel detector, irradiates the eluent with light from a light source (not shown), wavelength-disperses the light transmitted through the eluate, and determines the intensity of light at each wavelength by the PDA linear sensor. Detect almost simultaneously.
  • the detection signal repeatedly obtained by the PDA detector 15 is converted into a digital signal by the A / D converter 17 and then three-dimensional chromatogram data having three dimensions of time, wavelength, and absorbance (see FIG. 2A). Is output to the data processing unit 2.
  • the eluate that has passed through the PDA detector 15 (or a part of the eluate branched before the PDA detector 15) is introduced into an atmospheric pressure ionization mass spectrometer 16 provided at the rear stage of the LC unit 1.
  • the atmospheric pressure ionization mass spectrometer 16 includes a mass analyzer such as an ion source or a quadrupole mass filter by, for example, an electrospray ionization method or an atmospheric pressure chemical ionization method, and ionizes and generates components in the introduced eluate.
  • the detected ions are separated and detected at a mass-to-charge ratio m / z.
  • the detection signal repeatedly obtained by the atmospheric pressure ionization mass spectrometer 16 is converted into a digital signal by the A / D converter 18 and then three-dimensional chromatogram data having three dimensions of time, mass-to-charge ratio, and signal intensity ( The data is output to the data processing unit 2 as shown in FIG.
  • the data processing unit 2 outputs the UV data storage unit 20 for storing the three-dimensional chromatogram data (hereinafter referred to as “UV data”) output from the A / D converter 17 and the A / D converter 18.
  • MS data storage unit 21 for storing three-dimensional chromatogram data (hereinafter referred to as “MS data”), a wavelength chromatogram representing a time change of absorbance at a predetermined wavelength, or a signal intensity time at a predetermined mass-to-charge ratio
  • a chromatogram creation unit 22 that creates a mass chromatogram representing a change, a peak detection unit 23 that detects a peak corresponding to the target compound indicated by the operator in the wavelength chromatogram or the mass chromatogram, and a target compound Absorbance spectrum or mass spectrum similarity at each point in time during which the peak appears
  • Similarity calculation unit 24 for calculating, UV similarity storage unit 25 for storing the similarity of the absorbance spectrum, MS similarity storage unit 26 for storing the similarity of the mass spectrum, and the similarity of
  • the analysis control unit 19 controls the operation of each unit of the LC unit 1, the atmospheric pressure ionization mass spectrometer 16, and the like in order to perform LC / MS analysis on the sample.
  • the control unit 3 controls the entire system and user interface higher than the analysis control unit 19, and is connected to an operation unit 4 operated by an operator and a display unit 5 such as a monitor. Note that some or all of the functions of the data processing unit 2, the control unit 3, and the analysis control unit 19 are achieved by executing dedicated control / processing software installed in a personal computer or workstation.
  • the target compound is quantitatively analyzed by the LC / MS of this example
  • one or more mass-to-charge ratios characterizing the target compound are instructed by the operator, and the atmospheric pressure ionization mass spectrometer 16 uses the mass-to-charge ratio.
  • SIM measurement and scan measurement over a predetermined mass-to-charge ratio range are repeated at least within a predetermined time range near the retention time during which the compound elutes. Since mass spectrum data over a predetermined mass-to-charge ratio range is obtained for each scan measurement, as shown in FIG. 2 (b), the MS data storage unit 21 has one set for each predetermined time interval ⁇ t2. Mass spectrum data is stored.
  • the UV data storage unit 20 stores a predetermined spectrum as shown in FIG. One set of absorption spectrum data is stored for each time interval ⁇ t1. Normally, ⁇ t1 and ⁇ t2 are not the same.
  • FIGS. 2 (a) and 2 (b) the chromatogram derived from the target compound is executed mainly by the data processing unit 2 in a state where the UV data and the MS data are stored in the storage units 20 and 21, respectively.
  • the peak purity determination process will be described in detail with reference to FIGS.
  • FIG. 3 is a diagram illustrating an example of a mass chromatogram for explaining a peak purity determination method and a mass spectrum at a specific time point
  • FIG. 4 is an explanatory diagram of a method for calculating a mass spectrum similarity
  • FIG. 5 is a similarity for peak purity determination. It is a figure which shows the example of a display of a degree graph.
  • the chromatogram creation unit 22 receives this and reads MS data in a predetermined time range near the retention time of the designated target compound from the MS data storage unit 21.
  • the signal intensity at each time point in the mass-to-charge ratio of ions (generally called “quantitative ions”) that characterize the target compound most is extracted, and a mass chromatogram for the mass-to-charge ratio is created.
  • the peak detector 23 detects the peak near the holding time by examining the change in signal intensity in the time direction in the mass chromatogram, and obtains the time of the peak start point, peak end point, peak top, and the like. For example, the slope amount of the curve of the mass chromatogram shown on the right side of FIG.
  • the mass chromatogram of quantitative ions is not created from data collected by scan measurement, but from data collected by SIM measurement targeting quantitative ions performed in parallel with scan measurement. May be.
  • a mass chromatogram of quantitative ions obtained by SIM measurement is used, but the chromatogram used for peak purity determination is not limited thereto.
  • the similarity calculation unit 24 calculates the similarity of the mass spectrum obtained at each time point during the peak period from the start point to the end point of the detected peak as follows. As an example, it is assumed that a mass chromatogram at m / z 307 derived from the target compound is obtained as shown in FIG. 3, and that peak detection is performed for this and the peak period P is determined. FIG. 3 also shows a mass spectrum at each time of the peak start point, peak end point, and peak top included in this peak period, and a mass spectrum at a certain time outside the peak period (baseline mass spectrum). Yes.
  • the mass spectrum is also a signal for each mass-to-charge ratio, just as the absorbance spectrum can be regarded as a collection of absorbances for each wavelength It can be regarded as a set of strengths. Therefore, the two mass spectra Q 1 and Q 2 are expressed as vectors composed of the following elements.
  • the change in signal intensity in the horizontal axis direction is sharper in the mass spectrum than in the absorbance spectrum.
  • the mass spectrum is in comparison with the absorbance spectrum.
  • the resolution is high, noise peaks also appear relatively clearly. Therefore, in calculating the similarity based on the mass spectrum, it is desirable to remove the background noise data of the mass spectrum in advance. This is done by using a background noise removal process that is generally performed on a mass spectrum, for example, a process of subtracting a mass spectrum obtained when no component is present as a baseline mass spectrum. That's fine.
  • the similarity SI (MS) between two mass spectra is defined by the following equation (3) similar to equation (2).
  • the similarity SI (MS) of the mass spectrum at each time point during the peak period is obtained. Therefore, as shown in FIG. 4, the similarity of the mass spectrum M1 to be evaluated obtained at a certain time t1 during the peak period goes back by n scans (that is, n mass spectra) from that time.
  • the mass spectrum M2 obtained at time t2 is calculated as the reference mass spectrum. That is, first, the mass spectrum at the start point of the peak is set as the mass spectrum M1 to be evaluated, and the baseline mass spectrum obtained at a time point that is back by n scans is set as the reference mass spectrum M2.
  • the similarity SI (MS) is calculated by the equation (3).
  • the mass spectrum after one scan from the peak start point is set as the evaluation target mass spectrum M1, and the reference mass spectrum is also shifted backward by one scan (that is, the value of n is maintained).
  • the similarity should be almost 1 when the two mass spectra Q 1 and Q 2 are both in the peak period. If there is, the similarity decreases in a time range in which the overlap exists.
  • the above-mentioned baseline mass spectrum is subtracted as noise removal processing, only the peak at m / z 307 characterizing the target compound remains as the peak with high signal intensity, so there is a large signal intensity peak derived from impurities.
  • n determines the time interval between the two mass spectra when calculating the similarity is preferably determined according to the width of the impurity peak. Therefore, it is preferable that the operator can make an input setting from the operation unit 4.
  • the chromatogram creation unit 22 reads out UV data in a predetermined time range near the retention time of the designated target compound from the UV data storage unit 20, and calculates, for example, the absorbance at each time point at a typical absorption wavelength of the target compound. Extract and create a wavelength chromatogram.
  • the peak detection unit 23 detects a peak near the retention time in the wavelength chromatogram in the same manner as performed for the mass chromatogram, and obtains the time of the peak start point, peak end point, peak top, and the like. .
  • the similarity calculation unit 24 calculates the similarity of the absorbance spectrum obtained at each time point during the peak period from the start point to the end point of the detected peak, similarly to the similarity to the mass spectrum. That is, as described above, the two absorbance spectra S 1 and S 2 are expressed as vectors, and the similarity SI (UV) between the two absorbance spectra S 1 and S 2 is defined by the above equation (2). Similarly to the mass spectrum similarity SI (MS), the absorbance spectrum similarity SI (UV) at each time point during the peak period on the wavelength chromatogram is calculated. The similarity SI (UV) also approaches 1 as the two absorbance spectrum curves are closer.
  • the similarity SI (UV) at each time point corresponding to the peak of the target compound calculated based on the UV data is temporarily stored in the UV similarity storage unit 25. That is, for the same target compound, the mass spectrum similarity SI (MS) and the absorbance spectrum similarity SI (UV) in the vicinity of the appearance period of the chromatogram peak are obtained.
  • the similarity graph creation unit 27 reads the similarity data stored in the UV similarity storage unit 25 and the similarity data stored in the MS similarity storage unit 26, respectively, and the horizontal axis represents time and the vertical axis Create a graph with the similarity. Then, the two similarity graphs are superimposed on the same graph frame and drawn in different display colors, for example, and displayed on the screen of the display unit 5 through the control unit 3 (see FIG. 5). Even if the composition or molecular structure of the impurity overlapping the peak derived from the target compound is completely different from that of the target compound, the light absorption characteristics of the impurity may be similar to the light absorption characteristics of the target compound.
  • the similarity SI (UV) of the absorbance spectrum is close to 1
  • the similarity SI (MS) of the mass spectrum reflecting the difference in composition and structure is lower than 1.
  • the similarity SI (MS) of the mass spectrum is close to 1
  • the similarity SI (UV) of the absorbance spectrum reflecting the difference in the absorption characteristics is lower than 1.
  • a clear drop that is, a negative peak can be observed in the similarity SI (MS) of the mass spectrum as shown in a region C surrounded by a dotted line.
  • MS similarity SI
  • UV similarity SI
  • the operator can visually check such a similarity graph and judge the presence or absence of impurities by, for example, empirically judging the degree of depression.
  • the peak purity determination unit 28 automatically determines the purity of the peak based on the temporal change amount of the similarity in the above two similarity graphs. If there is an overlap of impurities in the peak derived from the target compound, a negative peak appears in any similarity SI (MS) or SI (UV) as shown in FIG. What is necessary is just to determine the presence or absence of impurities by calculating the difference between the similarity and the similarity immediately before the start point of the negative peak or immediately after the end point, and comparing this difference (or rate of change, etc.) with a threshold value. . Displaying such an automatic peak purity determination result on the display unit 5 can assist the operator's determination. Of course, automatic peak purity determination may be performed without displaying the similarity graph, and only the result may be displayed.However, by displaying the similarity graph together, the operator can visually determine whether the automatic determination is appropriate. I can confirm.
  • the impurity identification unit 29 executes component identification of the impurity. Since impurity identification is possible only when a negative peak is observed in the similarity graph of the mass spectrum, it is concluded that impurity identification is not possible unless this negative peak is observed. If a negative peak is observed in the similarity graph of the mass spectrum, the mass at an appropriate point in time when the similarity with the mass spectrum at the peak top of the negative peak is close to 1 and out of the negative peak period. Acquire the spectrum.
  • the impurity identifying unit 29 identifies the impurity by comparing the spectrum pattern of the differential mass spectrum with a component qualitative database provided in advance. In this identification, the approximate retention time of impurities estimated from the appearance position of the negative peak in the similarity graph can also be used. In addition, when definitive identification cannot be performed, a plurality of components may be extracted as candidates. Such impurity identification results are also displayed on the screen of the display unit 5 through the control unit 3. Thereby, when the impurity overlaps the peak derived from the target compound, it is possible to inform the operator what the impurity is.
  • the above embodiment is an example in which the present invention is applied to LC / MS, but it can also be applied to GC / MS in which the chromatograph is a gas chromatograph.
  • a chromatograph using a multi-channel detector such as a PDA detector is usually a liquid chromatograph.
  • the present invention can also be applied to an apparatus for processing data obtained by detection in (1).

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Abstract

Selon la présente invention, une unité (24) de calcul de similarité calcule, sur la base de données obtenues à partir d'un spectromètre (16) de masse, une similarité de motifs d'un spectre de masse à chaque point temporel durant une période couvrant toute la période d'apparition de pic de chromatogramme issu d'un composé cible, et d'un spectre de masse à des points temporels séparés par une période prescrite de ces points temporels. De plus, d'une manière similaire, une similarité pour un spectre d'absorption à chaque point temporel dans un pic de chromatogramme de longueur d'onde issu du même composé cible est calculée sur la base de données obtenues par un détecteur (15) PDA. L'unité (27) de création de graphique de similarité crée un graphique indiquant une variation temporelle pour chacune des similarités de spectre de masse et des similarités de spectre d'absorption, et affiche celui-ci sur un écran d'une unité (5) d'affichage par dessin de celui-ci recouvrant sur la même grille de graphique. Ainsi, une pureté de pic peut être déterminée de manière précise même lorsqu'une impureté qui a des caractéristiques d'absorption de lumière similaires au composé cible est présente.
PCT/JP2013/050062 2013-01-08 2013-01-08 Dispositif de traitement de données pour chromatographie-spectrométrie de masse WO2014108992A1 (fr)

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PCT/JP2013/050062 WO2014108992A1 (fr) 2013-01-08 2013-01-08 Dispositif de traitement de données pour chromatographie-spectrométrie de masse

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Cited By (6)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2016035167A1 (fr) * 2014-09-03 2016-03-10 株式会社島津製作所 Procédé et dispositif de traitement de données de chromatogramme
JP6037040B2 (ja) * 2013-10-16 2016-11-30 株式会社島津製作所 クロマトグラムデータ処理装置
GB2558043A (en) * 2016-10-14 2018-07-04 Micromass Ltd Combined gas chromatography vacuum ultra-violet detector with mass spectrometer or ION mobility spectrometer
CN108287200A (zh) * 2017-04-24 2018-07-17 麦特绘谱生物科技（上海）有限公司 质谱参照数据库的建立方法及基于其的物质分析方法
WO2018134998A1 (fr) * 2017-01-23 2018-07-26 株式会社島津製作所 Dispositif de traitement de données de chromatogramme
CN111551646A (zh) * 2020-05-15 2020-08-18 云南中烟工业有限责任公司 一种基于质谱相似度的色谱峰纯度判定方法

Families Citing this family (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP7312675B2 (ja) * 2019-11-11 2023-07-21 日本電子株式会社 マススペクトル処理装置及び方法

Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001108665A (ja) * 1999-10-05 2001-04-20 Shimadzu Corp クロマトグラフ用データ処理装置
JP2010181350A (ja) * 2009-02-09 2010-08-19 Shimadzu Corp クロマトグラフ用データ処理装置
WO2012004847A1 (fr) * 2010-07-05 2012-01-12 株式会社島津製作所 Dispositif de traitement pour affichage de chromatogrammes

Patent Citations (3)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP2001108665A (ja) * 1999-10-05 2001-04-20 Shimadzu Corp クロマトグラフ用データ処理装置
JP2010181350A (ja) * 2009-02-09 2010-08-19 Shimadzu Corp クロマトグラフ用データ処理装置
WO2012004847A1 (fr) * 2010-07-05 2012-01-12 株式会社島津製作所 Dispositif de traitement pour affichage de chromatogrammes

Cited By (13)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
JP6037040B2 (ja) * 2013-10-16 2016-11-30 株式会社島津製作所 クロマトグラムデータ処理装置
JPWO2015056311A1 (ja) * 2013-10-16 2017-03-09 株式会社島津製作所 クロマトグラムデータ処理装置
WO2016035167A1 (fr) * 2014-09-03 2016-03-10 株式会社島津製作所 Procédé et dispositif de traitement de données de chromatogramme
JPWO2016035167A1 (ja) * 2014-09-03 2017-06-08 株式会社島津製作所 クロマトグラムデータ処理方法及び装置
US10866221B2 (en) 2016-10-14 2020-12-15 Micromass Uk Limited Gas chromatography with vacuum ultra-violet detector and mass spectrometer or ion mobility spectrometer
GB2558043A (en) * 2016-10-14 2018-07-04 Micromass Ltd Combined gas chromatography vacuum ultra-violet detector with mass spectrometer or ION mobility spectrometer
GB2558043B (en) * 2016-10-14 2021-02-03 Micromass Ltd Combined gas chromatography vacuum ultra-violet detector with mass spectrometer or ION mobility spectrometer
WO2018134998A1 (fr) * 2017-01-23 2018-07-26 株式会社島津製作所 Dispositif de traitement de données de chromatogramme
JPWO2018134998A1 (ja) * 2017-01-23 2019-06-27 株式会社島津製作所 クロマトグラムデータ処理装置
CN108287200A (zh) * 2017-04-24 2018-07-17 麦特绘谱生物科技（上海）有限公司 质谱参照数据库的建立方法及基于其的物质分析方法
CN108287200B (zh) * 2017-04-24 2020-12-18 麦特绘谱生物科技（上海）有限公司 质谱参照数据库的建立方法及基于其的物质分析方法
CN111551646A (zh) * 2020-05-15 2020-08-18 云南中烟工业有限责任公司 一种基于质谱相似度的色谱峰纯度判定方法
CN111551646B (zh) * 2020-05-15 2023-09-22 云南中烟工业有限责任公司 一种基于质谱相似度的色谱峰纯度判定方法

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