# US 10,121,643 B2 · Chromatography/mass spectrometry data processing device > Agents: this data is available as JSON from the patentgrep API and MCP server — see https://patentgrep.com/llms.txt - Number: US 10,121,643 B2 - Document ID: US10121643B2 - Status: Granted - Kind: B2 - Application number: 14/339,607 - Filed: 2014-07-24 - Published: 2016-01-28 - Granted: 2018-11-06 - Earliest claimed: 2014-07-24 - Assignees: Shimadzu Corporation - Applicants: Shimadzu Corporation - Inventors: Katsuyuki Taneda - Web page: https://patentgrep.com/patent/US10121643B2 ## CPC - H01J 49/0036: {Step by step routines describing the handling of the data generated during a measurement} - G01N 30/72: Mass spectrometers {(mass spectrometers per se H01J49/00)} - G01N 30/8637: {Peak shape} - G16C 20/20: Identification of molecular entities, parts thereof or of chemical compositions - G01N 30/7206: {interfaced to gas chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)} - G01N 30/7233: {interfaced to liquid or supercritical fluid chromatograph (interfaces in general for introducing or extracting samples to be analysed with specially adapted mass spectrometer, see H01J49/04)} - H01J 49/0027: {Methods for using particle spectrometers} - H01J 49/0095: {Particular arrangements for generating, introducing or analyzing both positive and negative analyte ions (ion/ion reactions H01J49/0072)} - H01J 49/26: Mass spectrometers or separator tubes - H01J: ELECTRIC DISCHARGE TUBES OR DISCHARGE LAMPS (spark-gaps H01T; electric arc lamps H05B31/00; particle accelerators H05H) - G01N: INVESTIGATING OR ANALYSING MATERIALS BY DETERMINING THEIR CHEMICAL OR PHYSICAL PROPERTIES (measuring or testing apparatus or processes other than immunoassay, involving enzymes or microorganisms C12M, C12Q) - G16C: COMPUTATIONAL CHEMISTRY; CHEMOINFORMATICS; COMPUTATIONAL MATERIALS SCIENCE ## Abstract Using the intensity ratio of peaks on a standard mass spectrum of the target compound and peaks with the same m/z on the measured mass spectrum near the retention time of said compound, a scale factor waveform close to the chromatogram shape based on the target compound alone is computed, and m/z candidates for quantitation are extracted based on the correlation between the measured mass chromatogram of the target compound and the scale factor waveform. Furthermore, an intensity ratio is determined with reference to the m/z peaks showing the greatest scale factor on the measured mass spectrum at the measurement time point showing the greatest scale factor in the scale factor waveform, and m/z candidates for quantitation/confirmation are narrowed down based on whether they fall within an allowable range based on peak intensity ratio on the standard mass spectrum. ## Claims ### Claim 1 A chromatography/mass spectrometry data processing system which analyzes and processes data including mass-to-charge ratios, time, and signal intensities, wherein the chromatography/mass spectrometry data processing system is configured to repeatedly execute mass analysis across a predetermined mass-to-charge ratio range after separating components in a sample with a chromatograph, the chromatography/mass spectrometry data processing system comprising: a chromatograph configured to separate sample components; a mass spectrometer configured to ionize the sample components and sort ions according to mass-to-charge ratios; and a processor, wherein the processor includes: a) a chromatogram peak shape estimation unit which, using a plurality of intensity ratios, wherein each intensity ratio comprises: an intensity of a peak on a standard mass spectrum of a target compound, which is an object of analysis, and an intensity of peaks having a same mass-to-charge ratio on a measured mass spectrum at various measurement time points near a retention time of said target compound, estimates shapes of chromatogram peaks due to said target compound from which an influence of overlap of impurity components has been eliminated, based on a minimum value of one of the plurality of intensity ratios; b) a chromatogram peak correlation determination unit which determines a correlation between the shapes of the chromatogram peaks obtained by said chromatogram peak shape estimation unit and peaks of said target compound on a measured mass chromatogram obtained at each mass-to-charge ratio; c) a mass spectrum peak purity determination unit which determines mass spectrum peaks originating solely from the target compound based on: an intensity ratio of multiple peaks on the standard mass spectrum of said target compound, and an intensity ratio of multiple peaks having the same mass-to-charge ratio on the measured mass spectrum of the target compound at a specific measurement time point; and d) a mass-to-charge ratio derivation unit which, using determination results of said chromatogram peak correlation determination unit and determination results of said mass spectrum peak purity determination unit, derives a mass-to-charge ratio as a confirmation mass-to-charge ratio and/or quantitation mass-to-charge ratio used for quantitating said target compound. ### Claim 2 (depends on 1) The chromatography/mass spectrometry data processing system as described in claim 1, wherein said chromatogram peak shape estimation unit determines an intensity ratio Ps/Pr, wherein Ps comprises peak intensity on the measured mass spectrum, and Pr comprises peak intensity on the standard mass spectrum, of peaks having the same mass-to-charge ratio on the measured mass spectrum at a given measurement time point for the mass-to-charge ratio of all or some of the peaks on the standard mass spectrum of said target compound, wherein said chromatogram peak shape estimation unit takes a smallest intensity ratio Ps/Pr of multiple intensity ratios Ps/Pr as a scale factor at that measurement time point, and arranges scale factors determined at each measurement time point in a time series order to estimate shapes of the chromatogram peak of said target compound. ### Claim 3 (depends on 2) The chromatography/mass spectrometry data processing system as described in claim 2, wherein said mass spectrum peak purity determination unit determines a reference measurement time point and a reference mass-to-charge ratio which indicates the peak top of the chromatogram peak obtained by said chromatogram peak shape estimation unit, and taking as reference the ratio of the peak intensity for the reference mass-to-charge ratio on the standard mass spectrum of said target compound to the peak intensity at an arbitrary mass-to charge ratio, determines if the ratio of peak intensity for the reference mass-to-charge ratio on the measured mass spectrum at said reference measurement time point to the peak intensity at said arbitrary mass-to-charge ratio falls within a predetermined range in relation to said reference, and determines if the peak for the arbitrary mass-to-charge ratio is a mass spectrum peak originating solely from said target compound. ### Claim 4 (depends on 1) The chromatography/mass spectrometry data processing system as described in claim 1, wherein when the intensity of all or some of the peaks on the standard mass spectrum of said target compound is multiplied by a constant scaling factor and compared to the intensity of the peak having the same mass-to-charge ratio on the measured mass spectrum at a given measurement time point, said chromatogram peak shape estimation unit determines a constant scale factor, such that a former intensity does not exceed a latter intensity, and arranges the scale factors determined at each measurement time point in a time series order to estimate shapes of the chromatogram peaks of said target compound. ### Claim 5 (depends on 4) The chromatography/mass spectrometry data processing system as described in claim 4, wherein said mass spectrum peak purity determination unit determines a reference measurement time point and a reference mass-to-charge ratio which indicate the peak top of the chromatogram peak obtained by said chromatogram peak shape estimation unit, and taking as reference the ratio of the peak intensity for the reference mass-to-charge ratio on the standard mass spectrum of said target compound to the peak intensity at an arbitrary mass-to charge ratio, determines if the ratio of peak intensity for the reference mass-to-charge ratio on the measured mass spectrum at said reference measurement time point to the peak intensity at said arbitrary mass-to-charge ratio falls within a predetermined range in relation to said reference, and determines if the peak for the arbitrary mass-to-charge ratio is a mass spectrum peak originating solely from said target compound. ### Claim 6 (depends on 1) The chromatography/mass spectrometry data processing system as described in claim 1, wherein said mass spectrum peak purity determination unit determines a reference measurement time point and a reference mass-to-charge ratio indicates the peak top of the chromatogram peak obtained by said chromatogram peak shape estimation unit, and taking as reference the ratio of the peak intensity for the reference mass-to-charge ratio on the standard mass spectrum of said target compound to the peak intensity at an arbitrary mass-to charge ratio, determines if the ratio of peak intensity for the reference mass-to-charge ratio on the measured mass spectrum at said reference measurement time point to the peak intensity at said arbitrary mass-to-charge ratio falls within a predetermined range in relation to said reference, and determines if the peak for the arbitrary mass-to-charge ratio is a mass spectrum peak originating solely from said target compound. ### Claim 7 (depends on 1) The chromatography/mass spectrometry data processing system as described in claim 1, further comprising a display for displaying the confirmation mass-to-charge ratio and/or quantitation mass-to-charge ratio used for quantitating said target compound. ### Claim 8 A chromatography/mass spectrometry data processing method in which data including mass-to-charge ratios, time, and signal intensities are obtained by repeatedly executing mass analysis across a predetermined mass-to-charge ratio range after separating components in a sample with a chromatograph, the chromatography/mass spectrometry data method comprising: separating sample components with a chromatograph; ionizing the sample components and sorting ions according to mass-to-charge ratios with a mass spectrometer; a) using a plurality of intensity ratios, wherein each intensity ratio comprises: an intensity of a peak on a standard mass spectrum of a target compound which is an object of analysis, and an intensity of peaks having a same mass-to-charge ratio on a measured mass spectrum at various measurement time points near a retention time of said target compound, estimating, with a processor, shapes of chromatogram peaks due to said target compound from which an influence of overlap of impurity components has been eliminated, based on a minimum value of one of the plurality of intensity ratios; b) determining, with the processor, a correlation between the shapes of the obtained chromatogram peaks and peaks of said target compound on a measured mass chromatogram obtained at each mass-to-charge ratio; c) determining, with the processor, mass spectrum peaks originating solely from the target compound based on: an intensity ratio of multiple peaks on the standard mass spectrum of said target compound, and: an intensity ratio of multiple peaks having the same mass-to-charge ratio on the measured mass spectrum of the target compound at a specific measurement time point; d) using chromatogram peak correlation determination results and mass spectrum peak purity determination results, deriving, with the processor, a mass-to-charge ratio as a confirmation mass-to charge ratio and/or quantitation mass-to-charge ratio used for quantitating said target compound. ### Claim 9 (depends on 8) The chromatography/mass spectrometry data processing method as described in claim 8, further comprising displaying the confirmation mass-to-charge ratio and/or quantitation mass-to-charge ratio used for quantitating said target compound on a display. ### Claim 10 A chromatography/mass spectrometry data processing system which analyzes and processes data including mass-to-charge ratios, time, and signal intensities, and is configured to repeatedly execute mass analysis across a predetermined mass-to-charge ratio range after separating components in a sample with a chromatograph, wherein the chromatography/mass spectrometry data processing system comprises: a chromatograph configured to separate sample components; a mass spectrometer configured to ionize the sample components and sort ions according to mass-to-charge ratios; and a processor configured to: a) using a plurality of intensity ratios, wherein each intensity ratio comprises: an intensity of a peak on a standard mass spectrum of a target compound which is an object of analysis, and an intensity of peaks having a same mass-to-charge ratio on a measured mass spectrum at various measurement time points near a retention time of said target compound, estimate shapes of chromatogram peaks due to said target compound from which an influence of overlap of impurity components has been eliminated, based on a minimum value of one of the plurality of intensity ratios; b) determine a correlation between the shapes of the chromatogram peaks obtained by the processor and peaks of said target compound on a measured mass chromatogram obtained at each mass-to-charge ratio; c) determine mass spectrum peak purity by determining mass spectrum peaks originating solely from the target compound based on: an intensity ratio of multiple peaks on the standard mass spectrum of said target compound, and an intensity ratio of multiple peaks having the same mass-to-charge ratio on the measured mass spectrum of the target compound at a specific measurement time point; and d) using the correlation and the mass spectrum peak purity, derive a mass-to-charge ratio as a confirmation mass-to-charge ratio and/or quantitation mass-to-charge ratio used for quantitating said target compound. ### Claim 11 (depends on 10) The chromatography/mass spectrometry data processing system as described in claim 10, further comprising a display for displaying the confirmation mass-to-charge ratio and/or quantitation mass-to-charge ratio used for quantitating said target compound.