JP5365579B2 - Data processing equipment for chromatographic mass spectrometry - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To easily and swiftly support visual check for confirming appropriateness of a peak on an extraction ion chromatogram (EIC) used for identification. <P>SOLUTION: A measurement EIC121 of an ion of predetermined quantity of a target compound in the vicinity of holding time and a measurement EIC122 of an ion to be checked are indicated being overlapped with each other in a chromatogram display area 12. Also, a standard center line 123 corresponding to a standard value of a ratio of the ion to be checked, which represents an intensity ratio of the ion to be checked with respect to an intensity of the ion of predetermined quantity in the target compound, and an upper limit line 124 and a lower limit line 125 representing an allowance range of the intensity of the ion to be checked are displayed being overlapped with the EIC. An analyst determines if a top of an EIC peak of the ion to be checked is within a range between the upper limit line 124 and the lower limit line 125; thereby the peak used for identification can be determined if the same is generated by the target compound. <P>COPYRIGHT: (C)2012,JPO&amp;INPIT

Description

  The present invention relates to a data processing apparatus for processing data collected by a chromatograph mass spectrometer using a mass spectrometer (MS) as a detector for gas chromatograph (GC) or liquid chromatograph (LC). The present invention relates to a data processing technique related to a man-machine interface such as screen display processing and operation input processing in a chromatograph mass spectrometer.

  In the GC / MS analysis, various components contained in a test sample are temporally separated through a column, and ions generated from the separated components are mass-charge ratio ( m / z) to separate and detect with a detector. When identifying an unknown compound contained in a sample, usually, scan measurement in a predetermined mass range (m / z range) is repeatedly performed in the MS, and a mass spectrum is created for each scan measurement. The total ion current chromatogram (TIC) is a plot of the total ion intensity in each mass spectrum over time, focusing on ions with a specific mass-to-charge ratio. The extracted ion chromatogram (Extracted Ion Chromatogram = EIC) is obtained by plotting the intensity of the ions with time.

  When quantifying a compound contained in a sample by GC / MS analysis or LC / MS analysis, generally, ions characterizing the compound are determined as quantitative ions (also referred to as target ions), and the quantitative ions obtained by actual measurement are measured. In EIC, quantitative values, that is, component contents and concentrations are calculated from chromatogram peaks appearing near the retention time of the target compound. As the quantitative ion, an ion corresponding to a peak having a maximum signal intensity in a typical mass spectrum of the compound is usually selected.

  Although the above quantitative ions are ions that characterize each compound, the actual sample may contain various contaminants, and due to inappropriate analytical conditions, component separation in the preceding GC or LC is not possible. It may be sufficient and the components overlap. In such a case, it may be difficult to confirm whether or not the peak is indeed derived from the target compound only with the chromatogram peak of the quantitative ion. In such a case, apart from the quantitative ion, an ion having another mass-to-charge ratio that characterizes the compound is selected as the confirmation ion, and the signal intensity of the confirmation ion peak and the peak signal of the quantitative ion on the mass spectrum are selected. Using the relative ratio to the intensity (hereinafter referred to as “confirmed ion ratio”), confirmation that the chromatogram peak of the quantitative ion is derived from the target compound, that is, identification, is performed. In addition, in order to accurately confirm a quantitative ion peak of a certain compound, one type of confirmation ion is often insufficient, and a plurality of types of confirmation ions are often used for one compound ( Patent Document 1).

  In a conventional apparatus, the confirmation ion ratio obtained from the data obtained by mass spectrometry of the standard sample of the target compound is stored in advance in the storage unit as an ideal ratio, and the actual sample is analyzed. By comparing the value of the confirmed ion ratio obtained from the obtained data with the above ideal ratio, it is possible for the analyst to determine whether the confirmed ion ratio of the identified compound is appropriate. there were. However, such judgments based on numerical values are not very efficient and misjudgment is likely to occur. In addition, in order for an analyst to determine whether or not the compound is properly identified, it is necessary to visually confirm the shape and height of the peak on the EIC. It was difficult for analysts to judge whether it was appropriate based on the above.

  In particular, in the case of multi-component simultaneous analysis, an analyst visually confirms whether the peak on the EIC is appropriate based on the confirmed ion ratio, one for each of a large number of compounds ranging from several tens to several hundreds. It is necessary to confirm. For this reason, in order to increase the throughput of such work, analysts are required to make a judgment on the suitability of one compound in a short time, but it is difficult to make such a judgment in the short time with the conventional method as described above. In addition, there was a high possibility of causing misjudgment and omission of judgment.

JP 2006-189279 A

  The present invention has been made in view of the above-mentioned problems, and the object of the present invention is to perform work by an analyst when analyzing data collected by chromatographic mass spectrometry to perform component identification or quantitative analysis. It is an object of the present invention to provide a data processing apparatus for chromatograph mass spectrometry that can improve operational efficiency and reduce operational errors.

In order to solve the above problems, the present invention creates and displays an extracted ion chromatogram (EIC) for a specific mass-to-charge ratio based on data repeatedly collected over time by chromatographic mass spectrometry. In the data processor for chromatograph mass spectrometry to be displayed on the screen,
a) For each component, the retention time, the mass-to-charge ratio of the quantitative ion for calculating the quantitative value, and the mass-to-charge ratio of the confirmed ion to confirm that the peak of the quantitative ion is derived from the target component on the chromatogram And standard information storage means for storing a standard value of the confirmation ion ratio indicating the ratio of the intensity of the confirmation ion to the quantitative ion,
b) Based on the actual measurement data of the target component designated as the confirmation target among the various components stored in the standard information storage means, the extraction ion chromatogram of the quantitative ion and the confirmation ion of the target component is created. Chromatogram display processing means for displaying the same graph frame in an overlapping manner;
c) A standard value of the confirmation ion ratio of the target component corresponding to the confirmation ion whose extracted ion chromatogram is displayed by the chromatogram display processing means is obtained from the standard information storage means, and the extracted ion chromatogram of the confirmation ion As an index for determining the peak height appearing above, additional display processing means for graphically displaying information indicating the standard value on the extracted ion chromatogram displayed in an overlapping manner ,
It is characterized by having.

  The data processing apparatus for chromatographic mass spectrometry according to the present invention provides a dedicated computer program for realizing the functions corresponding to the above means on a general-purpose computer including a display unit, an operation unit (keyboard, pointing device, etc.) and the like. It can be realized by executing.

  Further, in the data processing apparatus for chromatographic mass spectrometry according to the present invention, typically, information indicating the standard value of the confirmation ion ratio of the target component may be displayed as a horizontal line superimposed on the EIC of the quantitative ion and the confirmation ion. . In addition, when there are a plurality of confirmation ions for one target component, EICs of the plurality of confirmation ions are displayed, for example, with different line colors, and the standard value of the confirmation ion ratio corresponding to each of the confirmation ions Similarly, the line color may be changed and displayed in an overlapping manner.

  In the data processing apparatus for chromatographic mass spectrometry according to the present invention, an analyst or the like selects in advance a component to be identified or a component to be checked for inclusion among various components stored in the standard information storage means. It is preferable to create a table in which these are registered, and the analyzer can select the target component by designating an arbitrary component from the table.

  If the selected target component is a component that is automatically identified using retention time, similarity of mass spectrum pattern, confirmation ion ratio, etc., the chromatogram display processing means displays on the EIC of the quantitative ion. What is necessary is just to display EIC which expanded the identified peak vicinity. On the other hand, if the selected target component is a component that has not been automatically identified, the peak closest to the retention time of the target component on the EIC of the quantitative ion is a chromatogram peak corresponding to the component. Therefore, it is only necessary to display an EIC in which the vicinity of the peak is enlarged.

  According to the data processing apparatus for chromatographic mass spectrometry according to the present invention, the peak waveform derived from the component appearing on the EIC of the confirmation ion of the target component and the ideal intensity ratio of the confirmation ion at a glance within the same graph frame. Can be confirmed. Therefore, the analyst can intuitively and quickly determine whether or not the peak height of the confirmed ion is about the same as the standard value of the confirmed ion ratio. In addition, since the waveform of the quantified ion peak and the confirmation ion peak of the target component by actual measurement can be confirmed, it is possible to simultaneously determine the collapse of the peak waveform caused by the overlap of non-target components such as impurities. . As a result, when performing tasks such as checking whether the target component is present in the sample and identifying the contained components, it is easy for the analyst to visually confirm the operation and improve work efficiency. In addition, work mistakes are reduced, so the reliability of the results increases.

  In the data processing apparatus for chromatographic mass spectrometry according to the present invention, preferably, the additional display processing means is an extracted ion chromatogram displaying information indicating an allowable intensity range centered on a standard value of a confirmed ion ratio. It is better to have a configuration that displays graphically on a gram. According to this configuration, it can be more easily determined whether or not the peak height of the confirmed ions is within an allowable range centered on the standard value of the confirmed ion ratio.

The schematic block diagram of one Example of GC-MS system containing the data processor which concerns on this invention. The schematic diagram which shows the data collection operation | movement in the GC-MS system of a present Example, and obtained data. The flowchart which shows an example of the procedure of the confirmation operation | work for the component identification in the GC-MS system of a present Example. The schematic diagram which shows an example of the display screen in the GC-MS system of a present Example.

  Hereinafter, a GC-MS system including a data processing apparatus for chromatographic mass spectrometry according to the present invention will be described with reference to the accompanying drawings. FIG. 1 is a schematic configuration diagram of a GC-MS system according to the present embodiment.

  This system includes a gas chromatograph (GC) 1 that temporally separates components contained in a sample, and a mass spectrometer (MS) that separates and detects each separated component according to a mass-to-charge ratio (m / z). ) 2 and a personal computer (PC) 3 for processing the data acquired by the MS 2. Dedicated data processing software is installed in the PC 3, and functions such as the illustrated data processing unit 4, measurement data storage unit 5, standard data storage unit 6 are realized by executing this software on the PC 3. Is done. The PC 3 is connected to an operation unit 7 and a display unit 8 which are pointing devices such as a keyboard and a mouse.

  FIG. 2 is a schematic diagram for explaining data collected during analysis in the GC-MS system. The data collection operation in the GC-MS system will be briefly described with reference to FIGS.

  When the sample is introduced into GC1, the components contained in the sample are separated and eluted in time while passing through a column (not shown). In the example of FIG. 2, six types of components A, B, C, D, E, and F are eluted with a time lag. In MS2, scan measurement involving mass scanning in a predetermined mass range is repeated at regular time intervals. By one scan measurement (mass scan), data (mass spectrum data) constituting one actually measured mass spectrum as shown in FIG. 2 is obtained. Therefore, the measured mass spectrum is obtained at each predetermined time interval by repeating the scan measurement at the predetermined time interval. The TIC is the sum of all the ion intensities contained in one measured mass spectrum and arranged in the time direction. The TIC is focused on only a specific mass-to-charge ratio in the time direction. The ones arranged are EICs. In the example of FIG. 2, the EIC at m / z = M1 corresponding to the peak appearing in the measured mass spectrum at time t1 is shown.

  In the GC-MS system of the present embodiment, the time from when a sample is introduced into GC1 (or when it is delayed for a predetermined time) to when it is appropriately delayed after the components in the sample have been eluted. The mass spectrum data is repeatedly collected as described above, and is collected into one data file and stored in the measurement data storage unit 5. The measurement data stored in the measurement data storage unit 5 is read into the data processing unit 4 as designated by the analyst, and is used for reanalysis for component identification and quantification.

  On the other hand, the standard data storage unit 6 includes various compound retention times, a mass-to-charge ratio of one quantitative ion, a mass-to-charge ratio of one to a plurality of confirmation ions, and standard values of confirmation ion ratios for each confirmation ion ((confirmation Ion intensity / quantitative ion intensity) × 100 [%]), standard mass spectrum, and the like are registered in advance. The data stored in the standard data storage unit 6 can be used as it is in publicly available databases such as NIST, Wiley, Drug, etc., or a part of it can be extracted and used. In addition, data that the device manufacturer creates and provides to the user, or data that the user acquires based on the measurement of the standard substance or the like may be used.

Next, characteristic data processing in the GC-MS system of the present embodiment, and more specifically, data processing for supporting confirmation work by an analyst at the time of component identification or the like will be described with reference to the flowchart of FIG. FIG. 4 is a schematic diagram showing an example of a screen displayed on the display unit 8 during the processing.
4A shows the data reanalysis screen 10 and FIG. 4B shows the confirmation ion ratio screen 20, which may be arranged side by side in the same screen, or the confirmation ion ratio is displayed on the data reanalysis screen 10. The screen 20 may be displayed in an overlapping manner. On the data reanalysis screen 10, a mass spectrum display area 11, a chromatogram display area 12, and a compound table display area 13 are each partitioned and arranged. Details of the graphs and tables displayed in each display area will be described later.

  When an analyst performs a predetermined operation on the operation unit 7 in order to specify data to be analyzed, the data processing unit 4 reads measurement data stored in the measurement data storage unit 5 as a processing target. Further, the data processing unit 4 extracts, from the standard data storage unit 6, information related to the compound specified in the method file that stores the analysis conditions used when acquiring the read measurement data, and stores the compound name and retention. A compound table listing the time and the like is created and displayed in the compound table display area 13 of the data reanalysis screen 10. A compound registered in the compound table is a compound that is desired to be identified in this reanalysis or to be confirmed whether or not it exists.

  Next, the data processing unit 4 performs automatic identification processing on the read measurement data using the compound table. For example, for each compound registered in the compound table, an EIC in the mass-to-charge ratio of quantitative ions is created from the measurement data, and a predetermined time centered on the retention time specified for that compound on the EIC A peak is detected within an allowable time width. Then, the measured mass spectrum of the peak at the time of peak top is compared with the standard mass spectrum defined for the compound, and when the similarity calculated according to a predetermined algorithm is equal to or greater than a threshold, the peak on the EIC is Judged to be the peak of origin. On the other hand, if the peak is not detected within a predetermined allowable time width centered on the retention time on the EIC in the mass-to-charge ratio of the quantitative ion, or if the similarity of the mass spectrum is low even if the peak is detected, The compound shall not be identified. In this way, automatic identification processing is executed for all the compounds registered in the compound table, and identification or non-identification is determined.

  However, since the automatic identification process is mechanically performed according to prescribed conditions, there is a possibility that erroneous identification or identification omission may occur depending on the deformation or distortion of the peak waveform shape due to overlapping of components or mixing of noise. Therefore, the analyst visually confirms the peak waveform shape and peak height on the EIC in the mass-to-charge ratio of the confirmed ions as follows, and checks whether the peak used for identification is appropriate. Check.

  The analyst operates the mouse to select and instruct a compound to be confirmed on the compound table displayed in the compound table display area 13 of the data reanalysis screen 10 as shown in FIG. 4A (step S1). ). In the example of FIG. 4A, “Fenobalbu” with ID #: 7 is designated, and the corresponding line in the compound table is shaded. The data processing unit 4 receives this compound selection instruction and determines whether or not the compound is an automatically identified compound (step S2).

  In the case of the automatically identified compound, the data processing unit 4 acquires information on the retention time for the specified compound and the mass-to-charge ratio of the quantification ion and the confirmation ion, and based on the measurement data, Create EIC and EIC of confirmation ions. Then, the EIC in a predetermined time range near the retention time of the compound is displayed in an overlapping manner in the same graph frame in the chromatogram display area 12. In FIG. 4A, the EIC of the quantitative ion having m / z 121.00 is indicated by reference numeral 121, and the EIC of the confirmation ion having m / z 150.00 is indicated by reference numeral 122. In this figure, the line types of both EICs are changed, but in actuality, it is only necessary to be able to identify both by changing the line color. Further, the data processing unit 4 creates an actually measured mass spectrum at the peak top time on the EIC of the quantitative ions based on the measured data, and displays this in the mass spectrum display region 11.

  In addition, the data processing unit 4 calculates the intensity of each confirmed ion from the area of the peak in the retention time appearing in the EIC of the quantitative ion and the EIC of the confirmed ion based on the actual measurement, and calculates the intensity of the confirmed ion with the intensity of the quantitative ion as 100%. Thus, the actually confirmed ion ratio is calculated. Based on the information such as the actually measured intensity value and the confirmed ion ratio, the standard value of the confirmed ion ratio stored in the standard data storage unit 6 (or registered in the compound table), FIG. The confirmation ion ratio table for the specified compound shown in FIG. 5 is created and displayed in the confirmation ion ratio screen 20. In the confirmation ion ratio table shown in FIG. 4B, the set% indicated by reference numeral 21 is the standard value of the confirmation ion ratio, the measured% indicated by reference numeral 22 is the actual confirmation ion ratio, and the allowable width indicated by reference numeral 23. Is the width of the confirmed ionic strength allowed around the standard value of the confirmed ion ratio.

  The data processing unit 4 graphically displays the standard value and allowable width of the confirmed ion ratio displayed in the confirmed ion ratio table in the chromatogram display area 12. That is, a horizontal standard center line 123 is drawn at the intensity position of the standard value (28% in this example) of the confirmed ion ratio when the peak top intensity in the EIC of quantitative ions is 100%. Further, an upper limit line 124 and a lower limit line 125 showing an allowable width (in this example, 30%) centered on the standard value of the confirmed ion ratio are also drawn (step S3). Since the standard center line 123 is a line indicating the standard value of the confirmed ion ratio, and the upper limit line 124 and the lower limit line 125 indicate the allowable range of the intensity of the confirmed ion, the height of the peak top of the EIC 122 of the confirmed ion is It is possible to determine whether or not the actually confirmed ion ratio is appropriate based on how far away from the standard center line 123 is within a range determined by the upper limit line 124 and the lower limit line 125.

  If it is determined in step S2 that the selected compound is not an automatically identified compound, the data processing unit 4 determines the retention time for the specified compound and the mass-to-charge ratio of the quantification ion and the confirmation ion. Information is acquired, and EIC of quantitative ions and EIC of confirmation ions are created based on the measurement data. Then, peak detection is performed on the EIC of quantitative ions, and the peak closest to the retention time of the compound among the detected peaks is regarded as the peak derived from the compound (step S4). Then, the EIC in a predetermined time range centered on the appearance time of this peak is displayed in an overlapping manner in the same graph frame in the chromatogram display area 12.

  Specifically, for example, a peak within the retention time ± α time range of the compound is extracted from the detected peaks, and when there are a plurality of peaks, the peak having the maximum peak area or the peak top value is obtained. The maximum peak may be regarded as a peak derived from the compound. At this time, if the time range of EIC displayed in the chromatogram display area 12 is set to the time range of retention time ± α, all the extracted peaks are displayed on the EIC.

  The rest of the processing is as described above, and the peak top intensity in the EIC of the quantitative ion is further set to 100 on the superimposed display of the EIC of the quantitative ion and the EIC of the confirmation ion displayed in the chromatogram display area 12. A horizontal standard center line is drawn at the intensity position of the standard value of the confirmed ion ratio with respect to%, and an upper limit line and a lower limit line showing an allowable width centered on the standard value of the confirmed ion ratio are also drawn (step S5). . Thereby, also about the compound which was not automatically identified, about the most likely peak on EIC, confirmation based on the waveform shape and confirmation ion ratio can be performed.

  In addition, if it is desired to perform the same confirmation for another compound different from the compound previously specified on the compound table, another compound may be specified on the compound table. As described above, according to the GC-MS system of the present example, the analyst was used to identify the target compound with a simple operation during the operation of component identification based on the already collected measurement data. It can be confirmed whether the peak on the EIC is appropriate in view of the ideal confirmation ion ratio.

  In the above embodiment, there is only one type of confirmation ion. However, when there are a plurality of types of confirmation ions, the measured EIC is displayed for all or part of the confirmation ions, and the confirmation ions of the displayed EIC are displayed. It is preferable to display the standard value and allowable width of the confirmed ion ratio in the display on the EIC. When there are a plurality of confirmation ions, the color of the line indicating the standard value of EIC or confirmation ion ratio may be different for each confirmation ion.

  Moreover, the said Example is only an example of this invention, and even if it changes suitably in the range along the meaning of this invention, correction, and addition, it is clear that it is included by the claim of this application.

1. Gas chromatograph (GC)
2. Mass spectrometer (MS)
3 ... Personal computer (PC)
4 ... Data processing unit 5 ... Measurement data storage unit 6 ... Standard data storage unit 7 ... Operation unit 8 ... Display unit 10 ... Data reanalysis screen 11 ... Mass spectrum display region 12 ... Chromatogram display region 13 ... Compound table display region 20 … Confirmation ion ratio screen

Claims (2)

In a data processor for chromatographic mass spectrometry that creates an extracted ion chromatogram for a specific mass-to-charge ratio and displays it on a display screen based on data repeatedly collected over time by chromatographic mass spectrometry,
a) For each component, the retention time, the mass-to-charge ratio of the quantitative ion for calculating the quantitative value, and the mass-to-charge ratio of the confirmed ion to confirm that the peak of the quantitative ion is derived from the target component on the chromatogram And standard information storage means for storing a standard value of the confirmation ion ratio indicating the ratio of the intensity of the confirmation ion to the quantitative ion,
b) Based on the actual measurement data of the target component designated as the confirmation target among the various components stored in the standard information storage means, the extraction ion chromatogram of the quantitative ion and the confirmation ion of the target component is created. Chromatogram display processing means for displaying the same graph frame in an overlapping manner;
c) A standard value of the confirmation ion ratio of the target component corresponding to the confirmation ion whose extracted ion chromatogram is displayed by the chromatogram display processing means is obtained from the standard information storage means, and the extracted ion chromatogram of the confirmation ion As an index for determining the peak height appearing above, additional display processing means for graphically displaying information indicating the standard value on the extracted ion chromatogram displayed in an overlapping manner ,
A data processing apparatus for chromatographic mass spectrometry, comprising: A data processing apparatus for chromatographic mass spectrometry according to claim 1,
The additional display processing means graphically displays, on a displayed extracted ion chromatogram, information indicating an allowable intensity range centered on a standard value of a confirmed ion ratio. Data processing device.

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