Chromatographic mass analysis device

Abstract

The present invention provides a chromatograph mass analysis device, comprising: a component separation unit (13) for separating components in a sample over time; a first detector (15) for acquiring measurement data of components contained in an effluent from the component separation unit (13) by an analysis method different from mass analysis; a mass analyzer (2) for acquiring mass analysis data, which includes intensity information of each mass-to-charge ratio of ions of components contained in the effluent from the component separation unit (13); a chromatogram generation unit (45) for generating a chromatogram representing intensity changes of the measurement data relative to time based on the measurement data of the first detector (15); an information extraction unit (46) for detecting a peak based on the intensity change relative to time of the mass analysis data, and extracting information including the time representing the peak; and a chromatogram display unit (48) for displaying the chromatogram together with additional information corresponding to the extracted time.

Description

Technical Field

[0001] The invention relates to a chromatograph mass analysis device. Background Art

[0002] Liquid chromatographs are widely used to identify or quantify components in a sample. In a liquid chromatograph, components in a sample are separated using a chromatographic column to detect each component.

[0003] When measuring the components in the sample liquid eluted from the chromatographic column, a liquid chromatograph equipped with an ultraviolet visible absorbance detector (UV detector) is often used. In a liquid chromatograph equipped with a UV detector, the sample liquid eluted from the chromatographic column is flowed into a measuring cell and irradiated with ultraviolet light of a specified wavelength, and the time change of the sample liquid's absorption of light is measured. After the measurement is completed, a chromatogram is obtained by graphing the time change of the light absorption. Then, the component is identified based on the position (retention time) of the peak of the chromatogram (qualitative analysis), and the component is quantified based on the area and height of the peak. Since the UV detector can perform highly reproducible measurements, it is possible to quantify known components with high accuracy.

[0004] Sometimes a mass analyzer is used as a detector of a liquid chromatograph. A liquid chromatograph equipped with a mass analyzer is called a liquid chromatograph mass analyzer. In a liquid chromatograph mass analyzer, the components contained in the sample liquid eluted from the chromatographic column are ionized, and their ion intensities are measured at each different mass-to-charge ratio. In a liquid chromatograph mass analyzer, three-dimensional data representing the ion intensity relative to the two axes of retention time and mass-to-charge ratio are obtained by scanning and measuring with a mass analyzer. Since the three-dimensional data contains information on the mass spectrum (mass-to-charge ratio to ion intensity), the components contained in the sample to be analyzed can be identified with higher accuracy (qualitative analysis) based on the detection of characteristic ions in each component.

[0005] Patent document 1 describes a liquid chromatograph mass spectrometer having both a UV detector and a mass analyzer. In the liquid chromatograph mass spectrometer, the sample solution eluted from the chromatographic column flows into the UV detector. If the UV detector detects a component, the mass analyzer continues to measure the sample solution flowing out of the UV detector. By repeatedly performing scanning measurements at short time intervals in the mass analyzer, a mass spectrum is acquired at each short time interval. Then, a chromatogram is generated based on the measurement data of the UV detector. In addition, based on the mass spectrum acquired at the time of the peak (or its vicinity) of the chromatogram, a pre-prepared compound database is referenced to identify the component corresponding to the peak. The chromatogram generated based on the measurement data of the UV detector is displayed on the screen together with the names of the components corresponding to each peak identified in this way.

[0006] Prior art literature

[0007] Patent Literature

[0008] Patent Document 1: Japanese Patent Application Publication No. 2001-165922 Summary of the invention

[0009] Technical problem to be solved by the invention

[0010] If the liquid chromatograph mass spectrometer described in Patent Document 1 is used, information on the components corresponding to each peak is displayed in a chromatogram with high reproducibility generated based on measurement data of a UV detector, so even unskilled workers can easily and accurately identify and quantify the components in the sample.

[0011] However, depending on the type of components contained in the sample, there are cases where ultraviolet light is not absorbed or absorbed less. Since the liquid chromatograph mass analyzer described in Patent Document 1 uses the detection of components by the UV detector as a trigger for mass analysis, components not detected by the UV detector are not measured by the mass analyzer, resulting in the problem of missing such components contained in the sample.

[0012] On the other hand, when measurements using a UV detector and measurements using a mass analyzer are performed separately, although the mass analyzer can be used to detect components that are not detected by the UV detector, the user needs to confirm the complex data obtained in the mass analyzer. In particular, for users who are not familiar with the mass analyzer, there is a problem that the burden of data confirmation operations increases.

[0013] Here, although the technical problems of the prior art are described using a liquid chromatograph mass spectrometer having a UV detector and a mass analyzer as an example, the same problems as described above also exist in liquid chromatograph mass spectrometers or gas chromatograph mass spectrometers having other detectors and mass analyzers.

[0014] The technical problem to be solved by the present invention is to provide a chromatograph mass analysis device, in which the user does not need to confirm the complex data obtained in the mass analyzer in detail, but can easily confirm the components that are difficult to detect by a method different from mass analysis.

[0015] Solutions for solving the above technical problems

[0016] The chromatograph mass spectrometer of the present invention completed in order to solve the above-mentioned technical problems comprises:

[0017] A component separation section that separates components in a sample over time;

[0018] a first detector for acquiring measurement data of components contained in the effluent from the component separation unit by an analysis method different from mass analysis;

[0019] a mass analyzer that acquires mass analysis data including intensity information for each mass-to-charge ratio of ions derived from components included in the effluent from the component separation section;

[0020] a chromatogram generating unit that generates a chromatogram representing intensity changes of the measurement data with respect to time based on the measurement data of the first detector;

[0021] an information extraction unit that detects a peak based on a change in intensity of the mass analysis data with respect to time, and extracts information including a time representative of the peak;

[0022] The chromatogram display unit displays the chromatogram together with the additional information corresponding to the extracted time.

[0023] Effects of the Invention

[0024] In the chromatograph mass spectrometer of the present invention, mass analysis data of components contained in the effluent from the component separation unit is acquired independently of the measurement value in the first detector, and information including the time representing the peak detected in the mass analysis data is extracted. Then, the additional information corresponding to the extracted time and the chromatogram generated based on the measurement data of the first detector are combined. Figure 1 Therefore, even if it is a component that is not detected by the first detector or a component whose measured value obtained by the first detector is small, it is possible to easily confirm that the component is detected by the mass spectrometer on the chromatogram of the first detector without confirming the mass analysis data. BRIEF DESCRIPTION OF THE DRAWINGS

[0025] Figure 1 It is a diagram showing the main components of an embodiment of a chromatograph mass spectrometer according to the present invention.

[0026] Figure 2 This is a flowchart related to the first analysis example using the liquid chromatograph-mass spectrometer of this embodiment.

[0027] Figure 3 This is a display example of the analysis result in the first analysis example.

[0028] Figure 4 This is another display example of the analysis result in the first analysis example.

[0029] Figure 5 This is another display example of the analysis result in the first analysis example.

[0030] Figure 6This is a diagram for explaining the detection of a TIC peak in a modification of the first analysis example.

[0031] Figure 7 It is the mass spectrum in the front of the peak, the peak top, and the back of the peak of TIC in the modification of the first analysis example.

[0032] Figure 8 This is a display example of the analysis result in a modification of the first analysis example.

[0033] Fig. 9 This is a flowchart related to the second analysis example using the liquid chromatograph-mass spectrometer of this embodiment.

[0034] Fig.10 This is a display example of the analysis results in the second analysis example.

[0035] Fig.11 This is a modification example of the display of the analysis result in the first analysis example or the second analysis example.

[0036] Fig.12 This is another modification example of displaying the analysis results in the first analysis example or the second analysis example.

[0037] Fig.13 This is still another modification of the display of the analysis result in the first analysis example or the second analysis example.

[0038] Fig.14 This is still another modification of the display of the analysis result in the first analysis example or the second analysis example. DETAILED DESCRIPTION

[0039] An embodiment of the chromatograph mass spectrometer of the present invention is described below with reference to the accompanying drawings. The chromatograph mass spectrometer of this embodiment is a liquid chromatograph mass spectrometer obtained by combining a mass spectrometer with a liquid chromatograph having a UV detector, and has a structure capable of executing all of the first analysis example, a variation of the first analysis example, and the second analysis example described later.

[0040] [Configuration of Liquid Chromatography Mass Analyzer]

[0041] Figure 1The structure of the main parts of the liquid chromatograph mass spectrometer of this embodiment is shown. The liquid chromatograph mass spectrometer of this embodiment is roughly composed of a liquid chromatograph 1, a mass analyzer 2, and a control unit 4 that controls their operations. The liquid chromatograph 1 includes: a mobile phase container 10 for storing a mobile phase; a pump 11 for sucking the mobile phase and delivering it at a constant flow rate (or flow velocity); a syringe 12 for injecting a predetermined amount of sample liquid into the mobile phase; a chromatographic column 13 for separating the components contained in the sample liquid over time; and a UV detector 15. The UV detector 15 includes: a flow cell 151 into which the sample liquid eluted from the chromatographic column 13 is introduced; a UV lamp 152 for irradiating the sample liquid flowing in the flow cell 151 with ultraviolet light of a predetermined wavelength; and a UV detection element 153 for measuring the intensity of the ultraviolet light that has passed through the flow cell 151. In addition, an automatic sampler 14 for introducing a plurality of liquid samples into the syringe 12 one by one is connected to the liquid chromatograph 1. The sample solution flowing out of the flow cell 151 is introduced into the electrospray ionization probe 201 of the mass spectrometer 2 through the pipe 16 .

[0042] The mass analyzer 2 has a multi-stage differential exhaust system between an ionization chamber 20 at approximately atmospheric pressure and an analysis chamber 23 at high vacuum after vacuum exhaust by a vacuum pump (not shown), and the multi-stage differential exhaust system includes a first intermediate vacuum chamber 21 and a second intermediate vacuum chamber 22 whose vacuum degree is increased in stages. The ionization chamber 20 is provided with an electrospray ionization probe (ESI probe) 201 for spraying while imparting electric charge to the sample liquid supplied from the liquid chromatograph 1. The ionization chamber 20 and the first intermediate vacuum chamber 21 are connected via a heating capillary 202 of a small diameter. The first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22 are separated by a skimmer 212 having a small hole at the top, and ion guides 211 and 221 for converging ions and transporting them to the next stage are provided in the first intermediate vacuum chamber 21 and the second intermediate vacuum chamber 22, respectively. A quadrupole mass filter 231 and an ion detector 232 are provided in the analysis chamber 23.

[0043] The mass analyzer 2 can perform selected ion monitoring (SIM) measurement and MS scanning measurement. In SIM measurement, the mass-to-charge ratio of ions passing through the quadrupole mass filter 231 is fixed, and only ions of this mass-to-charge ratio are detected. In MS scanning measurement, the mass-to-charge ratio of ions passing through the quadrupole mass filter 231 is scanned in a predetermined mass-to-charge ratio range, and ions in the predetermined mass-to-charge ratio range are detected for each mass-to-charge ratio.

[0044] The control unit 4 is provided with a storage unit 41 including a compound database 411, an excluded ion storage unit 412 and a delay time storage unit 413, and also includes a measurement condition setting unit 42, a measurement execution file generation unit 43, a measurement execution unit 44, a chromatogram generation unit 45, an information extraction unit 46, a component identification unit 47 and a chromatogram display unit 48 as functional blocks. The measurement condition setting unit 42 further includes an MS scan condition input acceptance unit 421 and a SIM condition input acceptance unit 422 as functional blocks. The information extraction unit 46 further includes an elution time extraction unit 461, a mass-to-charge ratio extraction unit 462 and a co-elution information extraction unit 463 as functional blocks. The entity of the control unit 4 is a personal computer, and if a predetermined analysis program pre-installed on the computer is executed, the functions of the above-mentioned units are executed by the processor of the personal computer. In addition, an input unit 6 and a display unit 7 are connected to the control unit 4.

[0045] The compound database 411 includes, for each of a plurality of compounds, the name of the compound, the molecular weight of the compound, the chemical formula, the structural formula and other structural information, the mass spectrum data obtained by performing MS scanning measurement on the standard sample of the compound, the mass-to-charge ratio value of the representative ion generated by each compound, etc. For example, when positive ions are measured in a liquid chromatograph mass spectrometer, the representative ions of the compound may include the addition of protons (H + ) of the protonated molecule, the mass-to-charge ratio of the + ), potassium (K + ), ammonia (NH4 + ) and other adduct ions, fragment ions that characterize the structure of the compound, etc.

[0046] The excluded ion storage unit 412 stores information on the mass-to-charge ratio of ions generated by substances other than the sample, such as the mobile phase used in the liquid chromatograph 1, together with the name of the mobile phase that generated the ions. The delay time storage unit 413 stores the difference (delay time) between the time when the components included in the sample solution are measured by the UV detector 15 and the time when the ions generated by the components included in the sample solution are detected by the mass spectrometer 2, and the relationship with the flow rate (or flow velocity) of the mobile phase. For example, the components that can be detected by both the UV detector 15 and the mass spectrometer 2 are measured by preliminary experiments, and the information on the delay time is generated based on the measurement results.

[0047] [First analysis example]

[0048] Next, refer to Figure 2 The steps of the first analysis example using the chromatograph mass spectrometer of this embodiment are described with reference to the flowchart of FIG. 1. In the first analysis example, MS scanning measurement is performed by the mass spectrometer 2 to analyze the components contained in the liquid sample.

[0049] When the user starts analyzing the liquid sample by a predetermined operation instruction, the measurement condition setting unit 42 displays a screen for the user to select whether to perform MS scan measurement or SIM measurement on the display unit 7. As described above, MS scan measurement is performed in the first analysis example.

[0050] When the user selects MS scan measurement (step 1), the MS scan condition input accepting unit 421 displays a screen for inputting a range of mass-to-charge ratios for mass scanning in MS scan measurement on the display unit 7. The range of the mass-to-charge ratio (m / z) is, for example, 100 to 2000, and can be appropriately set according to the mass-to-charge ratio of ions generated from the analysis target component.

[0051] If the user inputs a range of mass-to-charge ratios (step 2), the MS scan condition input accepting unit 421 will display a screen on the display unit 7 asking the user whether to set exclusion ions next. If the user chooses to set exclusion ions, the names of the mobile phases and compounds recorded in the exclusion ion storage unit 412 and the mass-to-charge ratios of ions generated by them are displayed on the display unit 7. If the user selects the names of the mobile phases and compounds, the mass-to-charge ratio associated with the selected mobile phases and compounds is set as the mass-to-charge ratio of the exclusion ions (step 3). Here, the case where the user personally selects the type of mobile phase or compound to set the exclusion ions is described, but it is also possible to configure the ions generated by the mobile phase to be automatically set as exclusion ions according to the type of mobile phase used in the liquid chromatograph 1.

[0052] When the setting of excluded ions is completed (or the user chooses not to set excluded ions), the measurement execution file generation unit 43 records an instruction to perform a mass scan within the mass-to-charge ratio range input by the user, and generates a measurement execution file in which excluded ions are set (when excluded ions are set) (step 4).

[0053] If the measurement execution file is generated by the measurement execution file generating unit 43, the measurement execution unit 44 instructs the user to start the measurement by displaying a measurement execution button on the display unit 7. If the user instructs to start the measurement, the measurement execution unit 44 controls the operation of each part of the liquid chromatograph 1 and the mass spectrometer 2 according to the record of the measurement execution file, and performs the MS scan measurement of the sample as follows. In addition, according to the user's instruction to start the measurement, the timing in the liquid chromatograph 1 and the mass spectrometer 2 is started, and the acquisition of measurement data is started. Alternatively, the timing in the liquid chromatograph 1 and the mass spectrometer 2 and the acquisition of measurement data can also be started while the sample is introduced from the automatic sampler 14 to the syringe 12.

[0054] After the measurement starts, the sample is introduced from the automatic sampler 14 into the syringe 12 (step 5). The sample introduced into the syringe 12 is introduced into the chromatographic column 13 along with the flow of the mobile phase, so that the components in the sample are separated. The sample liquid eluted from the chromatographic column 13 is sequentially introduced into the flow cell 151 of the UV detector 15. From the start of the measurement to the end of the measurement, ultraviolet light of a specified wavelength is irradiated from the UV lamp 152 to the flow cell 151, and the intensity of the ultraviolet light passing through the flow cell 151 is measured at specified time intervals by the UV detection element 153 (step 6). The measured values ​​of the intensity measured by the UV detection element 153 are sequentially saved in the storage unit 41. The above-mentioned specified wavelength is, for example, 254nm. The wavelength can be appropriately set according to the light absorption characteristics of the component to be analyzed.

[0055] The sample solution that has passed through the flow cell 151 is then introduced into the ESI probe 201 and ionized. In the mass analyzer 2, MS scanning measurement is performed on each ion derived from the sample solution within the mass-to-charge ratio range recorded in the measurement execution file (step 7). From the start of measurement to the end of measurement, MS scanning measurement is repeated at a predetermined time interval. The mass spectrum data obtained in each MS scanning measurement is sequentially stored in the storage unit 41.

[0056] After the measurement is completed, the chromatogram generation unit 45 reads the measurement data of the UV detector 15 stored in the storage unit 41. Then, the absorbance is calculated based on the intensity of the ultraviolet light detected by the UV detector 15, and a chromatogram is generated with the absorbance as the vertical axis and the time as the horizontal axis (step 8). Hereinafter, the chromatogram generated based on the measurement data obtained by the UV detector 15 is referred to as a UV chromatogram.

[0057] Next, the elution time extraction unit 461 generates total ion chromatogram (TIC) data by summing up the intensities of ions detected during one mass scan based on the mass analysis data repeatedly acquired by MS scanning measurement and stored in the storage unit 41. In addition, when the user sets the excluded ions, the intensity of the ions whose mass-to-charge ratio is set as the excluded ions is removed to generate TIC data. Thus, TIC data is obtained from which the influence of ions other than the sample, such as those originating from the mobile phase, is removed. If TIC data is obtained, the elution time extraction unit 461 further detects peaks from the TIC data using a prescribed peak detection algorithm. Then, information on the position (time) of the detected peak is extracted, and the time obtained by subtracting the delay time from it is saved in the storage unit 41 (step 9).

[0058] Here, the prescribed peak detection algorithm can apply a known method, for example, the following method can be applied: that is, within the entire measurement time range, the slope (Slope) of the chromatogram in the prescribed time range is calculated in sequence according to the detection intensity of the ions at a plurality of consecutive time points in the TIC data, and the peak start point, peak top, and peak end point are detected based on the slope (Slope) of the chromatogram at each time point. In this case, the time point at which the slope (Slope) changes to a prescribed value or more is detected as the peak start point, the time point at which the slope becomes near 0 is detected as the peak top, and the time point at which the slope changes to a value below the prescribed value is detected as the peak end point. The information of the position (time) at which the peak is detected extracted by the elution time extraction unit 461 can be information related to the representative time of the elution of the component in the sample as long as it is around the time point of the detected peak top, and is typically information corresponding to the time point of the peak top, or the time corresponding to the center of gravity position of the detected peak. For example, the center of gravity position of the peak can be calculated based on the intensity information between the detected peak start point and the peak end point, thereby obtaining the time corresponding to the center of gravity position of the peak.

[0059] In addition, in this analysis example, the detection intensity of ions in the total mass-to-charge ratio range (100 to 2000) of the mass scan is summed up to generate TIC data, but it is also possible to sum up the ion intensity of only a predetermined part of the mass-to-charge ratio range (for example, 300 to 2000) of the mass-to-charge ratio range of the mass scan to generate TIC data. In this case, the mass-to-charge ratio range that is the object of TIC data is input in advance by the user and included in the measurement execution file in advance.

[0060] In the liquid chromatograph mass spectrometer of the present embodiment, the UV detector 15 and the mass analyzer 2 are connected in series in the flow path pipe 16. After the components contained in the sample liquid are detected by the UV detector 15, they are detected by the mass analyzer 2 with a delay of a certain time (the time required for the components in the sample liquid detected in the flow cell 151 to be detected by the ion detector 232 of the mass analyzer 2). In the liquid chromatograph mass spectrometer of the present embodiment, since the timing and acquisition of measurement data in the liquid chromatograph 1 and the mass analyzer 2 are started at the same time, the position (time) of the peak detected from the TIC data by the elution time extraction unit 461 and the time (time when the peak appears in the UV chromatogram) detected by the UV detector 15 are offset by only the delay time. Therefore, the elution time extraction unit 461 reads the delay time that matches the measurement conditions (flow rate of the mobile phase, etc.) from the delay time stored in the delay time storage unit 413, and subtracts the delay time from the time of the peak in the TIC data.

[0061] If the information of the position (time) of the peak is extracted by the elution time extraction unit 461, the mass-to-charge ratio extraction unit 462 generates mass spectrum data based on the mass analysis data obtained at the position of each peak, and extracts the mass-to-charge ratio that meets the specified conditions from the mass spectrum (step 10), and saves it to the storage unit 41. Here, the mass-to-charge ratio that meets the specified conditions is typically the mass-to-charge ratio of the ion corresponding to the peak (base peak) with the highest detection intensity in the mass spectrum, or the mass-to-charge ratio of one or more ions corresponding to the peak with a detection intensity exceeding a predetermined threshold in the mass spectrum. In addition, the mass-to-charge ratio that is consistent with the representative mass-to-charge ratio of the compound registered in the compound database 411 can also be set as the mass-to-charge ratio that meets the specified conditions.

[0062] Next, the component identification unit 47 reads the mass spectrum data corresponding to each peak extracted from the TIC data from the storage unit 41, and compares it with the mass spectrum data included in the compound database 411 to identify the component (step 11). For example, the mass spectrum data is compared based on the position of the mass peak (mass-to-charge ratio) and the intensity ratio of each peak, and the component is identified when the consistency is greater than a predetermined value (identified with an accuracy greater than a predetermined value). In addition, when multiple mass spectrum data (substantially the same) with peaks at the same mass-to-charge ratio position are acquired continuously in time, the mass spectrum data with the largest intensity of the base peak is used as the mass spectrum data representing these multiple mass spectrum data and the component is identified. The information of the component identified by the component identification unit 47 is stored in the storage unit 41.

[0063] If the peak position (time) in the TIC data, the value representing the mass-to-charge ratio of each peak, and the information of the component identified based on the mass spectrum corresponding to each peak are obtained through the above-mentioned processing performed by the information extraction unit 46 and the component identification unit 47, the chromatogram display unit 48 adds this information to the UV chromatogram and displays it on the display unit 7 (step 12). This information is equivalent to the additional information in the present invention.

[0064] Figures 3 to 5 This is an example of the display of the chromatogram display unit 48. Figure 3 This is an example of what can be displayed with the minimum configuration of the chromatograph mass spectrometer of the present invention (excluding the mass-to-charge ratio extraction unit 462 and the component identification unit 47), in which a mark (arrow) showing the position of the peak in the TIC data is additionally displayed as additional information in the UV chromatogram. Figure 4 Except Figure 3 In addition to the example of , a value representing the mass-to-charge ratio of the mass spectrum acquired at the position of each peak of TIC is additionally displayed as additional information. Figure 5 Except Figure 4In addition to the example of , the name of the component identified based on the mass spectrum data acquired at the position of each peak of TIC is further displayed as additional information.

[0065] In addition, when the sample solution is ionized by the ESI probe, the positive ions generated are mainly molecular weight-related ions such as protonated molecules, and in the mass spectrum obtained by MS scanning measurement of these, peaks other than molecular weight-related ions may hardly appear. Therefore, it is sometimes difficult to identify all components based on the mass spectrum. In this case, only the name and mass-to-charge ratio of the base peak (in the ) are displayed for the components that have been identified with an accuracy rate greater than a predetermined value. Figure 5 In the example, "*" indicates the peak of the unidentified component. On the other hand, if an ionization method such as the electron ionization method used in a gas chromatograph mass spectrometer is used, which generates fragment ions during ionization, ions of multiple mass-to-charge ratios are detected by MS scanning measurement. In this case, identification of the components is relatively easy, and both the mass-to-charge ratio of the base peak and the name of each component can be displayed on the chromatogram.

[0066] exist Figures 3 to 5 In the example of the display, in a UV chromatogram having four peaks (hereinafter referred to as Peak 1, Peak 2, Peak 3, and Peak 4 in order from the peak with the shorter retention time), additional information (arrows) indicating that peaks of TIC data were detected at five positions (T1, T2, T3, T4, and T5) is added. For compound F (refer to Figure 5 ), additional information is added to the position of the UV chromatogram where no peak exists. This is because compound F does not absorb the ultraviolet light of the above-mentioned specified wavelength, and is only detected in the mass spectrometer 2. In this way, when a component (compound F in this example) that does not absorb ultraviolet light of the specified wavelength is included, the peak corresponding to the component does not appear in the UV chromatogram. Therefore, in the conventional chromatograph mass spectrometer such as that described in Patent Document 1, there is a problem that such a component is missed when it is included in the sample.

[0067] In contrast, in this analysis example, a UV chromatogram based on the measurement data obtained by the UV detector 15 is displayed together with the additional information. Therefore, even if a compound does not absorb ultraviolet light of a predetermined wavelength at all and cannot be detected by the UV detector 15, it is possible to easily confirm on the UV chromatogram that the component is detected by the mass spectrometer without confirming the mass analysis data.

[0068] [Variation of the first analysis example]

[0069] As described above, by detecting the elution time of a component derived from a sample based on the TIC chromatogram and adding additional information showing the detection time to the UV chromatogram, components not detected by the UV detector 15 can be confirmed on the UV chromatogram.

[0070] However, in TIC that does not process information about ion separation using mass-to-charge ratio, peaks of components eluting at very close times may not be sufficiently separated, making it difficult to determine the presence or absence of co-elution. Figures 3 to 5 In the case of peak 2, it appears that another peak overlaps behind peak 2 and co-elutes, but in the first analysis example, it is sometimes difficult to grasp such co-elution information on the UV chromatogram. This modification is preferably applied to such a situation, and the co-elution information extraction unit 463 is further used to grasp the presence or absence of co-elution. The following is an explanation of the processing using the co-elution information extraction unit 463.

[0071] First, the co-elution information extraction unit 463 detects the peaks of the chromatogram of the TIC data, such as Figure 6 As shown in FIG. 1 , the peak start point, peak top point and peak end point are determined. These points can be determined using the method described in the first analysis example.

[0072] Next, the mass spectra of the peak front part (between the peak start point and the peak top), the peak top, and the peak back part (between the peak top and the peak end point) within the detected peak range (the time range from the peak start point to the peak end point) are generated. Figure 7 Here, the mass spectrum of the front part of the peak is generated based on the mass spectrum data acquired at the middle time point between the peak start point and the peak top, and the mass spectrum of the rear part of the peak is generated based on the mass spectrum data acquired at the middle time point between the peak top and the peak end point.

[0073] Furthermore, the mass peaks of the three mass spectra are detected. For example, the detection is performed by extracting mass peaks with a predetermined intensity or above. Then, the mass-to-charge ratio ( Figure 7 m / z values: a~d) and intensity information ( Figure 7 The value recorded at the top of the mass peak of the mass spectrum shown). Figure 7 In the figure, the mass peak is illustrated in a bar shape for ease of understanding, but the actual mass peak has a width. Therefore, the intensity value of the peak top of the mass peak or the area value of the mass peak can be used in the intensity information of the mass peak.

[0074] Next, the intensity ratios between the mass peaks are calculated, and groups of mass peaks with a certain mass-to-charge ratio (m / z) are extracted from the mass spectrum of the front, top, and back parts of the peaks, and these are identified as mass peaks of ions originating from the same compound. Figure 7In the example, the intensity ratio of the three mass peaks with m / z a, c, and d is fixed at a:c:d=2:1:4 in the mass spectra of the front part, peak top, and back part of the peak, so it can be judged that they are mass peaks derived from the same compound.

[0075] On the other hand, for the mass peak of m / z=b, no other mass peaks with the same intensity ratio in the mass spectra of the front part, the peak top, and the rear part of the peak are found. In this case, it is determined that the mass peak of m / z=b is derived from ions of a component different from the components corresponding to the previous mass peak groups a, c, and d.

[0076] In this way, by using the co-elution information extraction unit 463, co-elution information of the co-elution of two different components, namely, the component corresponding to the ions of m / z=a, c, d and the component corresponding to the ion of m / z=b, is obtained within the time range of the peak detected from the TIC data.

[0077] Based on the co-elution information, the elution time extraction unit 461 extracts the time when the intensity of the mass peak of the ion of m / z=a, c, d identified as originating from the same component reaches the maximum. Then, the delay time is subtracted from the time to extract the elution time of the component (component C) corresponding to m / z=a, c, d. In addition, the time when the intensity of the mass peak of m / z=b identified as originating from a component different from the component reaches the maximum is extracted, and the delay time is subtracted to extract the elution time of the component (component B) corresponding to m / z=b.

[0078] In addition, the mass-to-charge ratio extraction unit 462 extracts the mass-to-charge ratio m / z=d with the largest intensity of the mass peak among m / z=a, c, d identified as originating from the same component as the mass-to-charge ratio representing the components corresponding to m / z=a, c, d, and extracts m / z=b identified as originating from a component different from the component as the representative mass-to-charge ratio of the component corresponding to m / z=b.

[0079] Next, the component identification unit 47 compares the mass peaks of the mass-to-charge ratios m / z=a, c, d and m / z=b identified as ions derived from different components with the mass spectrum data included in the compound database 411 to identify the compound.

[0080] Furthermore, the chromatogram display unit 48 displays the elution time, mass-to-charge ratio, and compound information extracted based on the co-elution information with the UV chromatogram. Figure 1 Start display. Figure 8An example of display in this variation is shown. In this display example, marks (arrows) showing the positions of peaks in TIC data, values ​​representing the mass-to-charge ratios of mass spectrum data acquired at the positions of each peak in TIC, and names of components identified based on the mass spectrum data acquired at the positions of each peak in TIC are additionally displayed in the UV chromatogram as additional information (the same information as in the first analysis example is shown). Figure 5 same additional information as in the display example).

[0081] In this modification, for Figures 3 to 5 Peak 2 suspected of co-elution shows, as additional information, a representative elution time T4 and a mass-to-charge ratio (93.70, ie, the mass-to-charge ratio b=93.70) corresponding to compound B in addition to compound C, so co-elution can be easily confirmed on the UV chromatogram.

[0082] In the above-mentioned modification, the mass spectrum of the front part of the peak is generated based on the mass spectrum data obtained at the middle time point between the peak start point and the peak top, and the mass spectrum of the rear part of the peak is generated based on the mass spectrum data obtained at the middle time point between the peak top and the peak end point, but the mass spectra can also be generated based on the mass spectrum data obtained at any multiple points between the peak start point and the peak top and the peak end point. In addition, the mass spectrum of the front part of the peak can be generated based on the mass spectrum data obtained at a time point before a specified time from the peak top, and the mass spectrum of the rear part of the peak can be generated based on the mass spectrum data obtained at a time point after a specified time from the peak top.

[0083] In addition, a mass spectrum can be generated based on the mass spectrum data obtained at the time point corresponding to the center of gravity of the peak to replace the time point of the peak top. Alternatively, instead of using the mass spectrum data obtained at the time point of the peak top or the center of gravity, the mass spectrum data at each time obtained by dividing the peak range (peak start point to end point) at equal intervals can be used to generate and confirm the mass spectrum. However, when detecting co-elution, it is expected that at least a mass spectrum at the time point of the peak top (or center of gravity) and one time point before and after it (front and back) for a total of three time points is generated and confirmed.

[0084] In the above modification, a group of mass peaks with a certain intensity ratio is associated with the same component, but the intensity ratio of the mass peaks does not need to be exactly the same. For example, a group of mass peaks whose intensity ratios differ within a specified range (for example, within ±10% relative to the intensity ratio at a certain time point) can be set as mass peaks derived from ions of the same component.

[0085] In the above-mentioned modification, m / z=d showing the maximum intensity among the mass peaks of m / z=a, c, and d of the mass-to-charge ratios of ions considered to be derived from the same component is extracted as the mass-to-charge ratio value representing the component, but the mass-to-charge ratio value representing each component may be extracted according to other criteria. For example, when extracting the mass-to-charge ratio value from each mass spectrum, ions derived from the mobile phase and the like stored in the excluded ion storage unit 412 may be set as excluded ions, and the mass-to-charge ratio of the ions representing each component may be extracted from the mass-to-charge ratio value of the ions excluding the excluded ions.

[0086] In the above modification, the peak is detected using TIC data, but the peak of the UV chromatogram may be detected, and the co-elution information may be extracted for the time range of the detected peak in the same manner as described above. However, in this case, the co-elution information cannot be extracted for the peak (peak 2, etc.) not detected by the UV detector 15. Therefore, it is desirable to detect the peak based on the TIC data obtained in the mass spectrometer as in the above modification.

[0087] The co-elution information extraction unit 463 can be configured as follows: that is, using the intensity information of each mass-to-charge ratio obtained by MS scanning measurement, a chromatogram for each mass-to-charge ratio, i.e., an extracted ion chromatogram (XIC), is generated, and peak detection is performed on each of the XICs to extract the co-elution information. However, in the above-mentioned modification, it is sufficient to narrow down the analysis to a few points in the peak range detected on the chromatogram of the TIC, and compared with detecting each peak of a large number of mass chromatograms, the co-elution information can be extracted more efficiently.

[0088] [Second analysis example]

[0089] Next, refer to Fig. 9 The flowchart of the second analysis example using the chromatograph mass spectrometer of this embodiment is used to explain the steps of the second analysis example. The second analysis example is an analysis example performed when the mass-to-charge ratio of the ions generated by the analysis target compound contained in the sample is known, and the SIM measurement is performed using the mass spectrometer 2 to analyze the components contained in the liquid sample. The purpose of performing this measurement is, for example, to confirm the separation characteristics of the liquid chromatograph 1 after the replacement of the chromatographic column 13 or the change of the measurement conditions.

[0090] When the user starts analyzing the standard sample by a predetermined operation instruction, the measurement condition setting unit 42 displays a screen for the user to select whether to perform MS scan measurement or SIM measurement on the display unit 7. As described above, SIM measurement is performed in the second analysis example.

[0091] If the user selects SIM measurement (step 21), the SIM condition input accepting unit 422 displays a screen on the display unit 7 for the user to input the mass-to-charge ratio of one or more ions used in the SIM measurement. Here, the user inputs the mass-to-charge ratio of the ion characterizing the compound for each compound to be measured. At this time, the user can input the value of the mass-to-charge ratio itself, or display a list of compounds registered in the compound database 411 through a prescribed operation, select a compound to be measured from them, and thereby input the mass-to-charge ratio of the compound. In addition, the value of the mass-to-charge ratio entered here can be one or more for a compound. The following is an example of inputting the mass-to-charge ratio of ions generated by compounds A to F.

[0092] When the user inputs the mass-to-charge ratio of ions used in the SIM measurement (step 22 ), the measurement execution file generation unit 43 generates a measurement execution file for sequentially measuring the mass-to-charge ratios input by the user (step 23 ).

[0093] When the measurement execution file is generated by the measurement execution file generating unit 43, the measurement execution unit 44 displays a measurement execution button on the display unit 7 to allow the user to instruct the start of measurement. When the user instructs the start of measurement, the measurement execution unit 44 controls the operation of each unit of the liquid chromatograph 1 and the mass spectrometer 2 according to the description of the measurement execution file, and performs SIM measurement of the sample as described below.

[0094] First, the sample is introduced from the automatic sampler 14 into the syringe 12 (step 24). The sample introduced into the syringe 12 is introduced into the chromatographic column 13 along with the flow of the mobile phase, and the components in the sample are separated. The sample liquid eluted from the chromatographic column 13 is sequentially introduced into the flow cell 151 of the UV detector 15. The flow cell 151 is irradiated with ultraviolet light of a specified wavelength by the UV lamp 152, and the intensity of the ultraviolet light that has passed through the flow cell 151 is detected at a specified time interval by the UV detection element 153 (step 25). The measured values ​​of the intensity measured by the UV detection element 153 are sequentially stored in the storage unit 41.

[0095] The sample solution that has passed through the flow cell 151 is then introduced into the ESI probe 201 and ionized. The ions generated by the sample solution are measured by the mass analyzer 2 (step 26). That is, the ions of the mass-to-charge ratio set for each compound among the ions originating from the sample solution are screened by the quadrupole mass filter 231 and detected by the ion detector 232. From the start of the measurement to the end of the measurement, the SIM measurement of the ions of the mass-to-charge ratio corresponding to the compounds A to F respectively recorded in the measurement execution file is repeatedly performed at a predetermined time interval. The intensity of the ions of the mass-to-charge ratio set for each compound is sequentially saved in the storage unit 41. Thus, the mass chromatogram data of the ions characterizing the compound are obtained for the compounds A to F respectively.

[0096] After the measurement is completed, the chromatogram generator 45 reads the measurement data of the UV detector 15 stored in the storage unit 41, calculates the absorbance based on the intensity of the detected ultraviolet light, and generates a chromatogram (UV chromatogram) with absorbance as the vertical axis and time as the horizontal axis (step 27).

[0097] Next, the elution time extraction unit 461 detects peaks based on the mass chromatogram data of each compound stored in the storage unit 41, extracts information on the position (time) of the detected peak (step 28), and stores it in the storage unit 41. For the peak detection of the mass chromatogram data of each compound, a known peak detection algorithm can be applied in the same manner as in the first analysis example. In addition, the component identification unit 47 determines the component corresponding to the peak based on the mass-to-charge ratio value obtained from the mass chromatogram where the detected peak appears (step 29).

[0098] If the peak position (time) of each mass chromatogram data and the information of the component corresponding to each peak are obtained by the elution time extraction unit 461 and the component identification unit 47, the chromatogram display unit 48 adds this information as additional information to the UV chromatogram and displays it on the display unit 7 (step 30). The additional information in this analysis example can include the peak position (time) of the chromatogram, the mass-to-charge ratio of the ion representing each compound, and the component information.

[0099] Fig.10 This is an example of the display of the chromatogram display unit 48. In this example, an arrow showing the position of a peak in the mass chromatogram data, the mass-to-charge ratio of the ion corresponding to the peak, and the name of the component are added to the UV chromatogram as additional information, and the color and line (in the Fig.10 An example of display in which a mass chromatogram corresponding to each compound is displayed in an overlapping manner (dashed line in the middle). Display / non-display of the mass chromatogram can be switched by a predetermined operation performed by the user.

[0100] exist Fig.10In the UV chromatogram shown, there are a total of 4 peaks (hereinafter referred to as peak 11, peak 12, peak 13 and peak 14, starting from the peak with the shorter retention time). On the other hand, 6 additional information are displayed. For example, for compound F, additional information is displayed at the position where there is no peak in the UV chromatogram. This is because compound F does not absorb the ultraviolet light of the above-mentioned specified wavelength and is only detected in the mass spectrometer 2. It is not necessarily known in advance whether the compound of the measurement object absorbs the light of the specified wavelength irradiated by the UV detector. Compound F is such an example. When the sample contains a component (compound F) that does not absorb ultraviolet light of the specified wavelength at all, the peak corresponding to the component itself does not appear. In the previous chromatograph mass spectrometer as described in Patent Document 1, such a component cannot be measured, but by using the chromatograph mass spectrometer of this embodiment, such a component can also be measured.

[0101] In addition, the position (time) of the peak 12 in this analysis example is also different from that in the first analysis example ( Figures 3 to 5 ) has multiple components (compounds B and C) co-eluting in the same manner. In the case of multiple components co-eluting like this, ions with different mass-to-charge ratios are detected at a predetermined intensity or above from the start time of peak 12 to the end time (i.e., different peaks of the mass chromatogram appear), and their additional information, peaks of the mass chromatogram, and UV chromatogram are compared. Figure 1 Therefore, it is easy to determine that a plurality of components co-elute in the time band of peak 12.

[0102] The above-described embodiment is merely an example and can be modified appropriately according to the spirit of the present invention.

[0103] Although MS scanning measurement is performed in the first analysis example and SIM measurement is performed in the second analysis example, when a mass analyzer such as a triple quadrupole mass spectrometer is used, product ion scanning measurement can be performed instead of MS scanning measurement, and MRM measurement can be performed instead of SIM measurement. In this case, it is sufficient to save the product ion scanning measurement conditions, product ion spectrum or MRM measurement conditions in the compound database 411 in advance.

[0104] In addition, in the schemes of the first and second analysis examples, by displaying the additional information extracted by the information extraction unit 46 as a mark at a time position on the UV chromatogram corresponding to the time representing the peak detected by the information extraction unit 46, it is possible to visually and intuitively grasp when the components in the sample are detected by the mass spectrometer 2, but it is not necessary to display the additional information at the corresponding time position on the UV chromatogram. For example, the additional information may be displayed on the UV chromatogram for the detected peak. Fig.11 , such a modification example is described.

[0105] In this case, first, peak detection is performed on the UV chromatogram using a known peak detection algorithm (for example, the same method as described in the first analysis example) to determine the range of each peak on the UV chromatogram. Then, based on the mass analysis data, it is determined which peak time range the elution time extracted by the information extraction unit 46 belongs to among the peak ranges on the UV chromatogram, thereby associating the peaks on the UV chromatogram with the additional information, and displaying a mark on each peak on the UV chromatogram to give the additional information corresponding to each peak.

[0106] Here, when a peak is detected by the measurement data of the mass spectrometer in a time band where no peak is detected on the UV chromatogram, additional information may be given at that time position ( Fig.11 In addition, when the information extraction unit determines that there is co-elution in the peak range where the peak is detected on the UV chromatogram (a modified example of the first analysis example and the second analysis example), information indicating the presence or absence of co-elution may be given to the UV chromatogram ( Fig.11 "*" etc.).

[0107] In addition, additional information can be displayed in table format. Figures 12-13 Such a modified example will be described.

[0108] Fig.12 This is an example of displaying the case where the additional information is formed as a table. Here, in addition to the elution time extracted by the elution time extraction unit 461 based on the mass analysis data, the additional information including the compound name identified by the component identification unit 47 and the mass-to-charge ratio extracted by the mass-to-charge ratio extraction unit 462 is displayed in the form of a table. Fig.12 In the example of , since the additional information is displayed outside the UV chromatogram, it is useful when, for example, there are multiple peaks on the UV chromatogram and it is very troublesome to individually confirm each peak based on the display of the chromatogram.

[0109] Fig.13 Apart from Fig.12 As an exception to the display of , information showing the presence or absence of peak detection in the UV chromatogram based on the measurement data obtained by the UV detector 15 (the rightmost example) is further displayed as additional information. In this example, the elution time extraction unit 461 performs peak detection on both the chromatogram of the mass analysis data (TIC, XIC) and the UV chromatogram, and determines whether a peak is also detected in the UV chromatogram at the time when a peak is detected in the chromatogram of the mass analysis data. As a result, in the case where there is a time when a peak is detected in the chromatogram of the mass analysis data but not in the UV chromatogram, this information is further displayed as additional information. Fig.13In the UV chromatogram, information indicating that no peak is detected is added to the elution time T2 corresponding to compound F and the elution time T4 corresponding to compound B. Thus, the user can more clearly understand the presence or absence of compounds whose peaks are detected only by the mass spectrometer 2. In addition, in this example, although compound B absorbs ultraviolet light of the above-mentioned predetermined wavelength, the absorbance of compound B is smaller than that of compound C eluting at a similar time. Therefore, in the UV chromatogram, the peak of compound B is buried in the peak of compound C, and no peak is detected at the elution time of compound C.

[0110] In this way, information showing the time when a peak is detected in the chromatogram of the mass analysis data but not in the UV chromatogram can also be shown in the form of Figures 3 to 5 , 8 and 10, the corresponding time positions on the UV chromatogram are marked as shown in the display example. Fig.14 Such an embodiment is shown. Fig.14 In the figure, by enclosing and displaying additional information corresponding to the elution times T2 and T4 of compounds F and B, respectively, the user can more clearly understand the presence or absence of peaks detected only by the mass spectrometer 2, wherein compounds F and B have no peaks detected in the UV chromatogram but have peaks detected in the chromatogram of the mass analysis data.

[0111] When the sample contains many types of compounds, the peaks of multiple compounds may be integrated into one in TIC and the peak may not be detected. Therefore, when there are many types of compounds or when it is assumed that the sample contains multiple compounds with similar elution times, peak detection based on XIC can more reliably detect the peaks of such multiple compounds.

[0112] The above embodiment is a mass spectrometer that combines a mass spectrometer and a liquid chromatograph with a UV detector, but a gas chromatograph can be used instead of a liquid chromatograph. In addition, a device that has a detector other than a UV detector and a mass spectrometer can also be used. For example, in the case of a liquid chromatograph, a diode array detector (PDA detector), a fluorescence spectrophotometer, or a differential refractive index detector can be used as the first detector.

[0113] In addition, regarding the chromatogram generated based on the measurement data in the first detector, an embodiment is described in which the absorbance relative to a predetermined wavelength (254 nm) obtained by using a UV detector is measured and a chromatogram showing the time change of the absorbance is generated, but as long as the chromatogram uses the intensity information of the measurement data measured based on the detection principle of the first detector, there are many possible schemes. For example, a predetermined wavelength range may be scanned and the absorbance of each wavelength may be measured to generate a chromatogram of the absorbance relative to the wavelength selected by the user, or a chromatogram of the cumulative value of the absorbance relative to the predetermined wavelength range may be generated.

[0114] In addition, in the above-mentioned embodiment, the components in the sample liquid are ionized by the electrospray ionization method in the mass spectrometer 2, but other ionization methods can also be used. For example, in a liquid chromatograph mass spectrometer, an atmospheric pressure chemical ionization (APCI) method can also be used. In addition, in a gas chromatograph mass spectrometer, various ionization methods such as an electron impact ionization (EI) method, a chemical ionization (CI) method, and a photoionization (PI) method can be used.

[0115] As the first detector for acquiring measurement data for generating a chromatogram, it is preferable to select a detector with high measurement reproducibility such as the UV detector 15 of the above-mentioned embodiment. By using such a detector, each component can be quantified with high precision based on the peak area and peak height of the chromatogram.

[0116] In the above embodiment, the first detector (UV detector 15) and the mass spectrometer 2 are arranged in series, but they can also be arranged in parallel and supplied separately with the sample solution eluted from the chromatographic column 13. In addition, a device other than the chromatographic column 13 can be used as the component separation unit of the chromatograph.

[0117] [plan]

[0118] Those skilled in the art may understand that the above exemplary embodiments are specific examples of the following schemes.

[0119] (Option 1)

[0120] A chromatograph mass spectrometer according to a first aspect of the present invention comprises:

[0121] A component separation section that separates components in a sample over time;

[0122] a first detector for acquiring measurement data of components contained in the effluent from the component separation unit by an analysis method different from mass analysis;

[0123] a mass analyzer for acquiring intensity information for each mass-to-charge ratio of ions containing components contained in the effluent from the component separation section;

[0124] a chromatogram generating unit that generates a chromatogram representing intensity changes of the measurement data with respect to time based on the measurement data of the first detector;

[0125] an information extraction unit that extracts information including time representative of a detected peak of intensity variation with respect to time in the mass analysis data;

[0126] The chromatogram display unit displays the chromatogram together with the additional information corresponding to the extracted time.

[0127] In the chromatograph mass spectrometer of the first aspect, mass analysis data of components contained in the effluent from the component separation unit is measured independently of the measurement value in the first detector, and additional information representing the time of the detected peak contained in the mass analysis data is extracted. Then, the additional information is combined with the chromatogram generated based on the measurement data of the first detector. Figure 1 Therefore, even for a component not detected by the first detector or a component whose measurement value by the first detector is small, it is possible to easily confirm on the chromatogram of the first detector that the component is detected by the mass spectrometer without confirming the mass analysis data.

[0128] (Option 2)

[0129] A chromatograph mass spectrometer according to a second aspect of the present invention is the chromatograph mass spectrometer according to the first aspect,

[0130] The chromatogram display unit displays the additional information at a position on the chromatogram corresponding to the time representing the peak detected by the information extraction unit.

[0131] In the chromatograph mass spectrometer of the second aspect, the additional information is displayed on the chromatogram at a time position or peak position corresponding to the time representing the peak detected by the information extraction unit. Therefore, when there is a component detected only by the mass spectrometer, its presence can be visually grasped.

[0132] (Plan 3)

[0133] A chromatograph mass spectrometer according to a third aspect of the present invention is the chromatograph mass spectrometer according to the first aspect or the second aspect,

[0134] The information extraction unit further determines whether there is a peak at a position corresponding to the time when the peak is detected on the chromatogram generated based on the measurement data of the first detector,

[0135] Further, when the information extracting unit determines that there is no peak, the chromatogram display unit adds information indicating that there is no peak in the measurement data of the first detector at the time when the peak is detected to the additional information.

[0136] In the chromatograph mass spectrometer of the third scheme, when a peak does not exist in the chromatogram generated based on the measurement data of the first detector at the time when a peak is detected from the mass analysis data, this information is displayed as additional information, thereby reliably understanding the presence of a component detected only by the mass spectrometer.

[0137] (Scheme 4)

[0138] A chromatograph mass spectrometer according to a fourth aspect of the present invention is the chromatograph mass spectrometer according to the first aspect or the second aspect,

[0139] The time representing the peak is the time when the intensity of the mass analysis data in the peak reaches the maximum, or the time corresponding to the center of gravity of the peak.

[0140] In the chromatograph mass spectrometer of the fourth scheme, since the time when the intensity of the mass analysis data reaches the maximum or the time corresponding to the center of gravity of the peak of the mass analysis data is set as the representative peak time, time information that correctly reflects the elution time of the component can be extracted as additional information.

[0141] (Scheme 5)

[0142] A chromatograph mass spectrometer according to a fifth aspect of the present invention is a chromatograph mass spectrometer according to any one of the first to fourth aspects, wherein

[0143] The intensity variation with respect to time of the mass analysis data is a time-series intensity variation of a summed intensity obtained by summing the intensities of the total mass-to-charge ratio range or the prescribed mass-to-charge ratio range measured.

[0144] In the chromatograph mass spectrometer of the fifth embodiment, since peaks are detected from the data of the total ion chromatogram, additional information including the time of the representative peak can be extracted in a shorter time than confirming the mass chromatogram of multiple or all mass-to-charge ratios within the measurement range.

[0145] (Scheme 6)

[0146] The chromatograph mass spectrometer of the sixth aspect of the present invention is the chromatograph mass spectrometer of the fifth aspect, further comprising an excluded ion storage unit storing information on the mass-to-charge ratio of excluded ions not added to the addition intensity.

[0147] The added intensity is an intensity value obtained by subtracting the ion intensity corresponding to the mass-to-charge ratio of the excluded ion.

[0148] In the chromatograph mass spectrometer of the sixth aspect, by setting the mass-to-charge ratio of ions generated from substances other than the sample in the mobile phase to excluded ions, a more accurate total ion chromatogram can be used by adding only the intensities of ions generated from the sample.

[0149] (Scheme 7)

[0150] A chromatograph mass spectrometer according to a seventh aspect of the present invention is a chromatograph mass spectrometer according to any one of the first to sixth aspects, wherein

[0151] The information extraction unit

[0152] extracting mass spectrum data from mass analysis data acquired at a plurality of time points within a time range in which the peak is detected,

[0153] detecting a plurality of mass peaks from each of the mass spectrum data at the plurality of time points,

[0154] determining a group of mass peaks having a common intensity ratio in the mass spectrum data at the plurality of time points,

[0155] detecting the time at which the intensity of at least one mass peak among the mass peaks included in the group reaches a maximum,

[0156] The detected time is defined as the time representing the peak.

[0157] In the chromatograph mass spectrometer of the seventh scheme, since a group of mass peaks having a common intensity ratio in mass peak data at multiple time points is determined as a mass peak corresponding to one component, information on co-elution can be efficiently extracted, and the presence or absence of co-elution can be determined on the UV chromatogram.

[0158] (Scheme 8)

[0159] A chromatograph mass spectrometer according to an eighth aspect of the present invention is a chromatograph mass spectrometer according to any one of the first to seventh aspects, wherein

[0160] The intensity variation of the mass analysis data with respect to time is the time series intensity variation of the mass analysis data measured for one or more individual mass-to-charge ratios.

[0161] In the chromatograph mass spectrometer of the eighth embodiment, since one or more ions of a single mass-to-charge ratio characteristic of a compound can be measured to obtain a mass chromatogram, the identification of the compound is higher than that of the total ion chromatogram, and since the S / N ratio is improved by eliminating noise, the peak detection accuracy is increased. This embodiment is particularly useful when a plurality of compounds are found to be co-eluting.

[0162] (Scheme 9)

[0163] A chromatograph mass spectrometer according to a ninth aspect of the present invention is a chromatograph mass spectrometer according to any one of the first to eighth aspects, wherein

[0164] The information extraction unit further comprises a mass-to-charge ratio extraction unit for extracting a mass-to-charge ratio satisfying a predetermined condition from the mass analysis data measured during the extraction time.

[0165] The additional information attached to the chromatogram includes information related to the extracted mass-to-charge ratio.

[0166] (Scheme 10)

[0167] A chromatograph mass spectrometer according to a tenth aspect of the present invention is the chromatograph mass spectrometer according to the ninth aspect,

[0168] The mass-to-charge ratio satisfying the specified condition is a mass-to-charge ratio having an intensity exceeding a specified intensity threshold, or a mass-to-charge ratio having a maximum intensity, in the mass analysis data acquired during the extraction time.

[0169] (Scheme 11)

[0170] The chromatograph mass spectrometer according to the eleventh aspect of the present invention is the chromatograph mass spectrometer according to the ninth aspect or the tenth aspect,

[0171] The information related to the mass-to-charge ratio includes the value of the mass-to-charge ratio, and at least one of a molecular weight, a chemical formula, a structural formula, and a compound name of a compound corresponding to the mass-to-charge ratio.

[0172] In the chromatograph mass spectrometers of the ninth to eleventh embodiments, a mass-to-charge ratio satisfying a predetermined condition (in the tenth embodiment, a mass-to-charge ratio having an intensity exceeding a predetermined intensity threshold value, or a mass-to-charge ratio having a maximum intensity) is extracted, and information related to the mass-to-charge ratio satisfying the predetermined condition (in the eleventh embodiment, a value of the mass-to-charge ratio, a molecular weight corresponding to the mass-to-charge ratio, a chemical formula, a structural formula, a compound name) is added as additional information. Therefore, the user can grasp information such as the mass-to-charge ratio of the compound eluted at that time without personally confirming the mass analysis data.

[0173] (Scheme 12)

[0174] A chromatograph mass spectrometer according to a twelfth aspect of the present invention is the chromatograph mass spectrometer according to any one of the first to eleventh aspects, further comprising:

[0175] Compound database, which stores mass analysis data for multiple compounds;

[0176] a component identification unit that identifies components contained in the effluent by comparing the mass analysis data acquired at the time extracted by the information extraction unit with the mass analysis data stored in the compound database,

[0177] The additional information includes information on the component identified by the component identification unit.

[0178] In the chromatograph-mass spectrometer of the twelfth aspect, since information on components included in the effluent from the component separation section is displayed on the chromatogram, the user can easily confirm the components included in the sample.

[0179] (Scheme 13)

[0180] A chromatograph mass spectrometer according to a thirteenth aspect of the present invention is the chromatograph mass spectrometer according to the twelfth aspect,

[0181] The mass analysis data measured during the time extracted by the information extraction unit is a mass spectrum indicating the relationship between the mass-to-charge ratio and the ion intensity.

[0182] In the chromatograph mass spectrometer of the thirteenth aspect, the components are identified by comparing the mass spectrum obtained by measurement with the mass spectrum recorded in the compound database. In comparing the mass spectra, information on the positions (mass-to-charge ratios) and intensities of the peaks appearing in the mass spectra can be used, so the components in the sample can be identified with high accuracy.

[0183] (Scheme 14)

[0184] A chromatograph mass spectrometer according to a fourteenth aspect of the present invention is the chromatograph mass spectrometer according to the twelfth aspect or the thirteenth aspect,

[0185] The compound database stores measurement conditions for measuring mass analysis data of the plurality of compounds.

[0186] The chromatograph mass analysis device further comprises:

[0187] a compound input receiving unit for receiving input of information specifying one or more compounds among the plurality of compounds;

[0188] a measurement execution file generating unit that reads the measurement conditions of the one or more compounds from the compound database and generates a measurement execution file that records the measurement conditions of the one or more compounds;

[0189] The measurement execution unit executes measurement based on the measurement conditions described in the measurement execution file.

[0190] The chromatograph mass spectrometer of the fourteenth aspect is useful in the following case: after changing the separation part or the type of mobile phase of the chromatograph, a sample containing known compounds is measured and the retention time of these compounds is confirmed to confirm the separation characteristics of the liquid chromatograph.

[0191] (Scheme 15)

[0192] A chromatograph mass spectrometer according to a fifteenth aspect of the present invention is a chromatograph mass spectrometer according to any one of the first to fourteenth aspects, wherein

[0193] further comprising a delay time storage unit for storing information on a delay time which is a difference between a time when the measurement data of the component is acquired in the first detector and a time when the mass analysis data of the component is acquired in the mass spectrometer,

[0194] The time representing the peak is the time corrected based on the delay time.

[0195] In the chromatograph mass spectrometer of the fifteenth aspect, since the acquisition time of the mass analysis data is corrected, the time consistency with the chromatogram generated based on the measurement data of the first detector is improved, and it becomes easy to grasp the information of the mass analysis data on the UV chromatogram.

[0196] (Scheme 16)

[0197] A chromatograph mass spectrometer according to a sixteenth aspect of the present invention is a chromatograph mass spectrometer according to any one of the first to fifteenth aspects, wherein

[0198] The chromatogram generating unit further generates a chromatogram representing intensity changes with respect to time of the mass analysis data,

[0199] The chromatogram display unit displays both a chromatogram indicating changes in measurement data of the first detector and a chromatogram indicating changes in intensity of the mass analysis data.

[0200] In the chromatograph mass spectrometer of the sixteenth aspect, even if a compound is not detected by the first detector or measurement data of sufficient intensity cannot be obtained, the compound can be quantified based on the chromatogram based on the mass spectrometry measurement data.

[0201] (Scheme 17)

[0202] A chromatograph mass spectrometer according to a seventeenth aspect of the present invention is a chromatograph mass spectrometer according to any one of the first to sixteenth aspects, wherein

[0203] The first detector is an ultraviolet-visible absorbance detector, a diode array detector, a fluorescence spectrophotometer or a differential refractive index detector,

[0204] The ionization method of the mass spectrometer is electrospray ionization or atmospheric pressure chemical ionization.

[0205] In the chromatograph mass spectrometer of the seventeenth embodiment, data can be obtained by using an ultraviolet-visible absorbance detector, a diode array detector, a fluorescence spectrophotometer, or a differential refractive index detector, which are particularly commonly used in liquid chromatographs. Even if these detectors cannot detect, additional information can be obtained by measuring the mass analysis data of ionizable components by the ESI method, the APCI method, or the like, and the chromatogram of the first detector. Figure 1 Start display.

[0206] Description of Reference Numerals

[0207] 1 Liquid Chromatograph

[0208] 10 Mobile phase container

[0209] 11 Pump

[0210] 12 Syringes

[0211] 13 Column

[0212] 14 Autosampler

[0213] 15. UV detector

[0214] 151 Flow Cell

[0215] 152 UV lamp

[0216] 153 UV detection element

[0217] 2 Mass Analyzer

[0218] 20 Ionization chamber

[0219] 201 ESI probe

[0220] 202 Heated capillary

[0221] 21. 1st intermediate vacuum chamber

[0222] 211 Ion Guide

[0223] 212 Skimmer Cone

[0224] 22. Second intermediate vacuum chamber

[0225] 23 Analysis Room

[0226] 231 Quadrupole Mass Filter

[0227] 232 Ion Detector

[0228] 4 Control Unit

[0229] 41 Storage

[0230] 411 Compound Database

[0231] 412 Exclusion ion storage unit

[0232] 413 Delay time storage unit

[0233] 42 Measurement condition setting section

[0234] 421 MS scanning condition input acceptance unit

[0235] 422 SIM condition input acceptance department

[0236] 43 Measurement execution file generation unit

[0237] 44 Measurement execution unit

[0238] 45 Chromatogram generation unit

[0239] 46 Information Extraction Department

[0240] 461 Elution Time Extraction Unit

[0241] 462 Mass-to-Charge Ratio Extraction Unit

[0242] 463 Co-elution Information Extraction Unit

[0243] 47 Component Identification Department

[0244] 48 Chromatogram display unit

[0245] 6 Input section

[0246] 7 Display unit.

Claims

1. A chromatograph mass analysis device, characterized in that: have: A component separation section that separates components in a sample over time; a first detector for acquiring measurement data of components contained in the effluent from the component separation unit by an analysis method different from mass analysis; a mass analyzer that acquires mass analysis data including intensity information for each mass-to-charge ratio of ions derived from components included in the effluent from the component separation section; a chromatogram generating unit that generates a chromatogram representing intensity changes of the measurement data with respect to time based on the measurement data of the first detector; an information extraction unit that detects a peak based on a change in intensity with respect to time in the mass analysis data and extracts information including a time representative of the peak; The chromatogram display unit displays the chromatogram together with the additional information corresponding to the extracted time.

2. The chromatograph mass spectrometer according to claim 1, characterized in that: The chromatogram display unit displays the additional information at a position on the chromatogram corresponding to a time representing a peak detected by the information extraction unit.

3. The chromatograph mass spectrometer according to claim 1, characterized in that: The information extraction unit further determines whether there is a peak at a position corresponding to the time when the peak is detected on the chromatogram generated based on the measurement data of the first detector. Furthermore, when the information extracting unit determines that there is no peak, the chromatogram display unit adds information indicating that there is no peak in the measurement data of the first detector at a time when the peak is detected to the additional information.

4. The chromatograph mass spectrometer according to claim 1, characterized in that: The time representing the peak is the time when the intensity of the mass analysis data in the peak reaches the maximum, or the time corresponding to the center of gravity of the peak.

5. The chromatograph mass spectrometer according to claim 1, characterized in that: The intensity variation with respect to time of the mass analysis data is a time-series intensity variation of a summed intensity obtained by summing the intensities of the total mass-to-charge ratio range or the predetermined mass-to-charge ratio range measured.

6. The chromatograph mass spectrometer according to claim 5, characterized in that: further comprising an excluded ion storage unit for storing information on the mass-to-charge ratio of excluded ions that are not added to the addition intensity, The added intensity is an intensity value obtained by subtracting the ion intensity corresponding to the mass-to-charge ratio of the excluded ion.

7. The chromatograph mass spectrometer according to claim 1, characterized in that: The information extraction unit extracting mass spectrum data based on mass analysis data acquired at multiple time points within the time range in which the peak is detected, Detecting a plurality of mass peaks based on the respective data of the mass spectrum data at the plurality of time points, determining a group of mass peaks having a common intensity ratio in the mass spectrum data at the plurality of time points, detecting the time at which the intensity of at least one mass peak among the mass peaks included in the group reaches a maximum, The detected time is defined as the time representing the peak.

8. The chromatograph mass spectrometer according to claim 1, characterized in that: The intensity variation with respect to time of the mass analysis data is the time series intensity variation of the mass analysis data measured for one or more individual mass-to-charge ratios.

9. The chromatograph mass spectrometer according to claim 1, characterized in that: The information extraction unit further comprises a mass-to-charge ratio extraction unit, which extracts a mass-to-charge ratio satisfying a predetermined condition based on the mass analysis data measured during the extraction time. The additional information added to the chromatogram includes information related to the extracted mass-to-charge ratio.

10. The chromatograph mass spectrometer according to claim 9, characterized in that: The mass-to-charge ratio satisfying the predetermined condition is a mass-to-charge ratio having an intensity exceeding a predetermined intensity threshold value or a mass-to-charge ratio having a maximum intensity in the mass analysis data acquired during the extraction time.

11. The chromatograph mass spectrometer according to claim 9, characterized in that: The information related to the mass-to-charge ratio includes the value of the mass-to-charge ratio, and at least one of a molecular weight, a chemical formula, a structural formula, and a compound name of a compound corresponding to the mass-to-charge ratio.

12. The chromatograph mass spectrometer according to claim 1, characterized in that: Further possesses: Compound database, which stores mass analysis data for multiple compounds; a component identification unit that identifies components contained in the effluent by comparing the mass analysis data measured during the time extracted by the information extraction unit with the mass analysis data stored in the compound database, The additional information includes information on the component identified by the component identification unit.

13. The chromatograph mass spectrometer according to claim 12, characterized in that: The mass analysis data measured during the time extracted by the information extraction unit is a mass spectrum indicating the relationship between the mass-to-charge ratio and the ion intensity.

14. The chromatograph mass spectrometer according to claim 12, characterized in that: The compound database stores measurement conditions for measuring mass analysis data of the plurality of compounds. The chromatograph mass analysis device further comprises: a compound input receiving unit for receiving input of information specifying one or more compounds among the plurality of compounds; a measurement execution file generating unit that reads the measurement conditions of the one or more compounds from the compound database and generates a measurement execution file that records the measurement conditions of the one or more compounds; The measurement execution unit executes measurement based on the measurement conditions described in the measurement execution file.

15. The chromatograph mass spectrometer according to claim 1, characterized in that: further comprising a delay time storage unit for storing information on a delay time which is a difference between a time when the measurement data of the component is acquired in the first detector and a time when the mass analysis data of the component is acquired in the mass spectrometer, The time representing the peak is the time corrected based on the delay time.

16. The chromatograph mass spectrometer according to claim 1, characterized in that: The chromatogram generating unit further generates a chromatogram representing intensity changes with respect to time of the mass analysis data, The chromatogram display unit displays both a chromatogram indicating changes in measurement data of the first detector and a chromatogram indicating changes in intensity of the mass analysis data.

17. The chromatograph mass spectrometer according to claim 1, characterized in that: The first detector is an ultraviolet-visible absorbance detector, a diode array detector, a fluorescence spectrophotometer or a differential refractive index detector, The ionization method of the mass spectrometer is electrospray ionization or atmospheric pressure chemical ionization.

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