JP7105049B2 - Mass spectrometry data processing device and mass spectrometry data processing method - Google Patents

Description

The present invention relates to a mass spectrometry data processing apparatus and a mass spectrometry data processing method for processing mass spectrometry data obtained by sequentially performing mass spectrometry on sample components separated by chromatography.

In chromatographic mass spectrometry, the chromatographic method is used to sequentially ionize the components separated in time, and the ions are separated according to the mass-to-charge ratio [m/z] by a mass spectrometer and detected by a detector. It is an analytical method that allows quantitative analysis of known components and qualitative analysis of unknown components. A mass spectrometer that performs such analysis is equipped with a data processing device for data processing of the mass spectrum (mass spectrum) of each component detected by the chromatograph along with the elapsed time (retention time).

For example, in the case of qualitative analysis, this data processing device creates a total ion current chromatogram (total ion current chromatogram: hereinafter referred to as TICC) in which the signal intensity corresponding to the total amount of ions of an unknown component is plotted with retention time. do. Then, the mass spectrum at the peak position of the chromatogram obtained by peak search on TICC is extracted, and the sample component of the chromatogram peak is identified by comparing this mass spectrum with the library.

On the other hand, in the case of quantitative analysis, the data processor creates a chromatogram that plots the signal intensity of ions of known components against retention time, and calculates the concentration from the compound peak area obtained from this chromatogram and the calibration curve. Calculate and quantify known components.

Patent Document 1 discloses a technique for securing a longer monitoring time for target ions and necessary identified ions than in the conventional art by not executing the detection itself of the identified ions when the target ions to be identified do not appear. It is

JP 2006-189279 A

However, it was not possible to immediately determine whether or not the compound to be identified was detected only by the function of displaying the peak position of the compound to be identified on the display unit, which the conventional mass spectrometer has. For this reason, when using the functions of conventional mass spectrometers, it is necessary to start qualitative analysis software separate from the mass spectrometer and perform work to confirm the detected sample components, which places a burden on the operator. was

In addition, the function of matching with the National Institute of Standards and Technology (NIST) library in real time each time a chromatogram peak is detected, which is a feature of conventional mass spectrometers, does not leave the results after analysis on the display. Therefore, it was not possible to easily obtain analytical results.

Further, in the technique disclosed in Patent Document 1, identification ions (reference ions) are not detected unless target ions (quantitative ions) are detected. For this reason, target ions (quantitative ions) and identification ions (reference ions) cannot be detected at the same time, and it takes time to identify the compound to be identified.

SUMMARY OF THE INVENTION The present invention has been made in view of such circumstances, and an object of the present invention is to quickly obtain analysis results of sample components.

A mass spectrometry data processing apparatus according to the present invention is a mass spectrometry data processing apparatus for identifying sample components based on data obtained by sequential mass spectrometry of sample components separated according to retention times by a chromatograph. A chromatogram creation unit that creates a chromatogram corresponding to each mass-to-charge ratio of an integer mass from data obtained by mass spectrometry in a time width of a preset identification condition, and based on the identification condition , Identification processing for identifying whether or not the actually measured sample components obtained from the chromatogram are the target compounds to be identified is performed in real time according to the timing of the sample components being separated by the chromatograph and subjected to mass spectrometry. and an image data creation unit for creating image data for displaying the identification result indicating whether or not the target compound is detected by the identification processing.
Further, in the mass spectrometry data processing apparatus according to the present invention, after calculation of the peak detection time range of the target compound by the identification unit based on the image data, a predetermined time width centered on the retention time corresponding to the compound to be identified Displaying a first detection result display screen including a compound peak appearance prediction region for each target compound to be identified displaying the peak detection position of the spectrum extracted from the chromatogram peak in the region, and displaying the first detection result display. After the screen is displayed, if the identification unit detects the compound to be identified within a predetermined time span around the retention time corresponding to the target compound, the peak detection position of the extracted spectrum of the target compound to be identified is displayed. and a display unit for displaying a second detection result display screen including the expected compound peak appearance region of the target compound, wherein the image data created by the image data creation unit is displayed on the first detection result display screen and the second detection result display screen. is displayed on the display unit.

According to the present invention, when the sample component is identified as the compound to be identified based on the chromatogram, the identification result is displayed on the display unit. It is possible to quickly grasp whether or not
Problems, configurations, and effects other than those described above will be clarified by the following description of the embodiments.

BRIEF DESCRIPTION OF THE DRAWINGS It is a block diagram which shows the outline of the mass spectrometer based on the 1st Embodiment of this invention. FIG. 3 is an explanatory diagram showing a configuration example of data processed by a mass spectrometry data processing device; FIG. 3 is an explanatory diagram showing an example of a mass spectrum; FIG. 4 is an explanatory diagram showing an example of a method of extracting spectra from peaks of a chromatogram; FIG. 4A shows an example of peaks detected on the TICC, and FIG. 4B is an explanatory diagram showing an example of the spectrum at central position B (peak top position) in FIG. 4A. FIG. 4 is an explanatory diagram showing an example of a method of extracting spectra from peaks of a chromatogram; 5C shows an example of the spectrum at tail position A (position on the left side of the tail of the peak) in FIG. 4A, and FIG. 5D shows an example of the spectrum at tail position C (position on the right side of the tail of the peak) in FIG. 4A. 5E is an explanatory diagram showing an example of a mass spectrum extracted from the TICC peak in FIG. 4A. FIG. 4 is an explanatory diagram showing the contents of a quantification condition setting file used in the mass spectrometer according to the first embodiment of the present invention; FIG. 6A shows an example of compound information, FIG. 6B shows an example of peak detection conditions, and FIG. 6C is an explanatory diagram showing an example of compound identification conditions. FIG. 5 is an explanatory diagram showing a display example of a detection result display screen according to the first embodiment of the present invention; 4 is a flowchart (part 1) showing an example of main processing of the mass spectrometer according to the first embodiment of the present invention; 2 is a flowchart (part 2) showing an example of main processing of the mass spectrometer according to the first embodiment of the present invention; 4 is a flow chart showing an example of first identification processing for identifying a target compound based on retention time [RT] of quantification conditions according to the first embodiment of the present invention. 9 is a flowchart showing an example of main processing of the mass spectrometer according to the second embodiment of the present invention; FIG. 10 is a flow chart showing an example of second identification processing for identifying a target compound based on the I/Q ratio error rate according to the second embodiment of the present invention; FIG. FIG. 11 is a flow chart showing an example of main processing of the mass spectrometer according to the third embodiment of the present invention; FIG. FIG. 10 is a flow chart showing an example of third identification processing for identifying a target compound based on spectral similarity shown as a library search result according to the third embodiment of the present invention; FIG.

Embodiments for carrying out the present invention will be described below with reference to the accompanying drawings. In the present specification and drawings, constituent elements having substantially the same function or configuration are denoted by the same reference numerals, thereby omitting redundant description.

[First embodiment]
<Mass spectrometer>
FIG. 1 is a configuration diagram showing an outline of a mass spectrometer according to a first embodiment. The mass spectrometer 1 according to the first embodiment shown in FIG. 1 sequentially performs mass spectrometry on sample components separated by chromatography. The mass spectrometry data processing device 1a of the embodiment is provided. Details of these components are described below.

<Sample separation unit>
The sample separation unit 101 is an example of a chromatograph that separates a mixture sample to be analyzed for each component. The sample separation unit 101 includes a sample introduction unit 101a for introducing a mixture sample to be analyzed, and a column 101b for separating the components of the sample introduced from the sample introduction unit 101a. The column 101b is filled with a stationary phase through which the sample introduced from the sample introduction part 101a passes. The components temporally separated according to the speed of passage through the stationary phase are supplied to the mass spectrometer 102 with a retention time [RT: Retention Time] specific to each component.

As the sample separation unit 101, for example, a gas chromatograph is used, but the present invention is not limited to this, and a liquid chromatograph or other chromatographs may be used.

<Mass spectrometer>
The mass spectrometry unit 102 sequentially ionizes each component separated by the sample separation unit 101 and supplied with a time lag, and further separates the ions of the ionized components according to the mass-to-charge ratio [m/z]. to detect. Such a mass spectrometry unit 102 includes an ionization unit 102a, a mass separation unit 102b, and a detector 102c.

The ionization section 102a sequentially ionizes the components supplied from the sample separation section 101 . In the ionization section 102a, molecular ions of the component supplied from the sample separation section 101 and a plurality of fragment ions obtained by splitting the molecular ions are generated.

The mass separation unit 102b separates the ions supplied from the ionization unit 102a by mass-to-charge ratio [m/z], and allows only ions with a specific mass-to-charge ratio [m/z] to pass through and reach the detector 102c. Let In this mass separation unit 102b, by scanning the mass-to-charge ratio [m/z] of ions reaching the detector 102c, each ion reaches the detector 102c sequentially for each mass-to-charge ratio [m/z]. This process is repeated at regular intervals. Such a mass separation unit 102b is of an appropriate type depending on the combination with the ionization unit 102a.

The detector 102c detects the signal intensity [I] of the ions separated according to the mass-to-charge ratio [m/z] in the mass separator 102b. Then, the detector 102c obtains a mass spectrum signal for each scan by extracting the obtained signal intensity [I] corresponding to the scan of the mass-to-charge ratio [m/z]. A mass spectrum signal obtained by the detector 102c is supplied to the mass spectrometry data processing device 1a.

<Mass spectrometry data processor>
The mass spectrometry data processing device 1a identifies the sample components based on the data obtained by sequentially performing mass spectrometry on the sample components separated by the sample separation unit 101 according to the retention time. For this reason, the mass spectrometry data processing device 1a stores in the storage unit 11 data that associates the mass spectrum signal detected by the detector 102c with the retention time [RT], and based on this data, the sample to be analyzed conduct a qualitative analysis of

Such a mass spectrometry data processing apparatus 1a includes an input/output control unit 10, a storage unit 11, a mass spectrum extraction unit 12, a chromatogram creation unit 13, an identification unit 14, an image data creation unit 15, an operation unit 16, and a display unit. 17.

The input/output control unit 10 controls the operation timings of the other units according to a preset program and an operator's operation from the operation unit 16, thereby executing mass spectrometry data processing. The input/output control unit 10 is connected to other units constituting the mass spectrometry data processing device 1a and the detector 102c of the mass spectrometry unit 102. FIG.

As described above, the storage unit 11 stores data in which the mass spectrum signal detected by the detector 102c is associated with the retention time [RT].

FIG. 2 is an explanatory diagram showing a configuration example of data stored in the mass spectrometry data processing device. As shown in FIG. 2, the input/output control unit 10 receives the mass spectrum signals detected by the detector 102c for each repeated scan described above in order according to the retention time [RT]. The storage unit 11 stores chromatograms for each mass-to-charge ratio [m/z] created by the chromatogram creation unit 13, which will be described later. Here, as shown by the dashed line in FIG. 2, a graph of signal intensity [I] of ions having a specific mass-to-charge ratio versus retention time [RT] is called a mass chromatogram.

The chromatogram has a peak at a predetermined extraction time position [tp] within the retention time range [Tw] set for the retention time [RT]. A noise extraction time position [tn] is set around the extraction time position [tp]. The noise extraction time position [tn] is set to subtract the noise height from the peak height of the extraction time position [tp]. For example, the noise extraction time position [tn] is set near the bottom of the peak having the peak top at the extraction time position [tp], that is, at the edge of the baseline. However, the noise extraction time position [tn] is not limited to the edge of the baseline, and various positions can be selected by the operator of the mass spectrometer 1 .

Further, the storage unit 11 stores data in which mass spectra of known substances are associated with compound names and structural formulas as a library. FIG. 3 is a diagram showing an example of a mass spectrum. This data may be the same as the data stored in the NIST library.

Based on the data stored in the storage unit 11, the mass spectrum extraction unit 12 creates a total ion current chromatogram by integrating the signal intensity [I] detected by the detector 102c for each retention time [RT]. (See Figure 2).

After creating the TICC, the mass spectrum extraction unit 12 performs a series of TICC-based spectrum extractions according to a normal automatic peak detection (so-called peak search) program. In such automatic peak detection, noise component removal of the signal intensity [I] is also automatically performed. Noise component removal is typically performed by using the signal intensity [I] at the peak top of each mass-to-charge ratio [m/z] appearing at each peak position on the TICC, and the signal at the left and right tail positions of the peak top. It is carried out by subtracting the averaged value of the intensity [I] as the background. A specific example of noise component removal will be described later with reference to FIGS. 4 and 5. FIG. The mass spectrum extraction unit 12 extracts a mass spectrum for each retention time [RT] corresponding to each peak on TICC by such automatic peak detection.

Further, the chromatogram creation unit 13, for example, in a predetermined retention time range [Tw] set by input from the operation unit 16, based on the data stored in the storage unit 11, each mass-to-charge ratio of the integer mass Create a chromatogram corresponding to [m/z] (see Figure 2). In FIG. 2, only four chromatograms corresponding to four mass-to-charge ratios [m/z] are indicated by dashed lines for explanation.

The identification unit 14 performs identification processing for identifying that the actually measured sample component obtained from the chromatogram is the compound to be identified based on preset identification conditions. The identification unit 14 according to the present embodiment can identify sample components by using a plurality of identification processes (first to third identification processes) to be described later. Then, the identification unit 14 performs identification processing in real time in accordance with the timing when the sample components are mass-analyzed by the sample separation unit 101 . In addition, the identification unit 14 can perform identification processing at a timing different from that of the mass spectrometry after the sample component is mass-analyzed by the sample separation unit 101 .

The image data creation unit 15 creates image data for displaying the data created by the mass spectrum extraction unit 12 and the chromatogram creation unit 13 and the identification results of the identification unit 14 on the display unit 17 . The details of the image data will be described in the subsequent mass spectrometry data processing method.

The operation unit 16 inputs various settings related to data processing to be executed in the mass spectrometry data processing apparatus 1a. Various settings related to data processing are, for example, settings of a retention time range [Tw] for creating a chromatogram in the chromatogram creating unit 13 . The operation unit 16 may be, for example, a keyboard, a mouse, or a touch panel type operation unit integrally formed with the display unit 17 .

The display unit 17 displays an image based on the image data created by the image data creation unit 15 . As an image displayed on the display unit 17, for example, there is a detection result display screen 20 shown in FIG. 7, which will be described later.

<Mass spectrum extraction method>
Although any method of extracting a mass spectrum from a chromatogram peak can be used in this embodiment, an example of the extraction method will be described below.
4 and 5 are explanatory diagrams showing an example of a method for extracting mass spectra from chromatogram peaks.

FIG. 4A is an explanatory diagram showing an example of peaks detected on TICC. The horizontal axis of FIG. 4A is retention time [RT], and the vertical axis is signal intensity [I]. Peaks detected by TICC are displayed, for example, as shown in FIG. 4A. Here, the center of the peak where the retention time [RT] is "11.2" is called the center position B, the left tail position of the center position B is called the tail position A, and the right tail position of the center position B is called It is called a hem position C.

Inside the sample separation unit 101 and the mass spectrometry unit 102, components other than the sample (air components in the room where the mass spectrometer 1 is placed, rubber packing components, moisture components) and the like reach the ionization unit 102a. Sometimes. When these components are ionized by the ionization unit 102a, peaks are detected as background ions. Therefore, when extracting mass spectra from chromatogram peaks, it is necessary to remove the influence of background ions.

FIG. 4B is an explanatory diagram showing an example of a mass spectrum at center position B (peak top position) in FIG. 4A.
FIG. 5C is an explanatory diagram showing an example of the mass spectrum at tail position A (position on the left side of the tail of the peak) in FIG. 4A.
FIG. 5D is an explanatory diagram showing an example of the mass spectrum at tail position C (position on the right side of the tail of the peak) in FIG. 4A.
FIG. 5E is an explanatory diagram showing an example of a mass spectrum extracted from the TICC peak in FIG. 4A. The horizontal axis of FIGS. 4B to 5E is the mass-to-charge ratio [m/z], and the vertical axis is the signal intensity [I].

In FIG. 4B, when the peak of “129” with the largest mass-to-charge ratio [m / z] is set as the base peak, and the signal intensity [I] of this base peak is 100%, other mass-to-charge ratios [m /z] are shown. Similarly, in FIGS. 5C and 5D, when the signal intensity [I] of “57” having the largest mass-to-charge ratio [m/z] is 100%, other mass-to-charge ratios [m/z] The relative signal strength [I] at is shown.

Here, the mass spectrum extraction unit 12 averages the mass spectra of the tail positions of the left and right peaks (averages the intensity for each m / z) from the mass spectrum of the top positions of the peaks detected on the chromatogram. Subtract stuff as background. At this time, the following formula (1) is used.

B - (A + C) / 2 ... formula (1)

Specifically, the mass spectrum extraction unit 12 performs a process of subtracting the average of the mass spectra of FIGS. 5C and 5D from the mass spectrum of FIG. 4B. As a result, as shown in FIG. 5E, for example, the background of the mass spectrum with a mass-to-charge ratio [m/z] of "57" disappears. Mass spectra can thus be extracted from the chromatogram peaks.

FIG. 6 is an explanatory diagram showing the contents of a quantitative condition setting file used in the mass spectrometer 1. As shown in FIG. The quantitative condition setting file is stored in the storage unit 11, and items are added or information is edited by the operation unit 16 operated by the user. Based on the quantification condition setting file read out from the storage unit 11, the identification unit 14 selects a compound (also referred to as a “target compound”) corresponding to the quantification conditions set in the quantification condition setting file as a compound to be identified. identify.

FIG. 6A is an explanatory diagram showing an example of compound information. The compound information consists of fields of compound name, RT, quantification ion, reference ion, I/Q ratio, library name, and spectrum ID. These parameters can be set for each compound.

The compound name field stores the name of the target compound. In FIG. 6A, for example, information about compounds of chloroform and benzene is stored.
The RT field stores the retention time [RT] of the target compound in minutes.
The quantification ion field stores the mass-to-charge ratio [m/z] of the quantification ion of the target compound.
The reference ion field stores the mass-to-charge ratio [m/z] of the reference ion of the target compound. Note that the mass-to-charge ratios [m/z] of a plurality of reference ions may be stored with respect to the mass-to-charge ratio [m/z] of one quantitative ion.

The intensity ratio between the quantification ion and the reference ion is set in the I/Q ratio field. The I/Q ratio represents the ratio of the intensity of reference ions to the intensity of quantitation ions, as shown in the following equation (2).

I/Q ratio=(Intensity of reference ion)/(Intensity of quantification ion) Equation (2)

In formula (2), the ion with the highest intensity in one mass spectrum is taken as the quantified ion. If there are multiple reference ions, multiple I/Q ratios are set. All of the I/Q ratios are values smaller than one.

A library name of a library in which the mass spectrum of the target compound is registered is set in the library name field. When using the NIST library, the NIST library name is set. The identification unit 14 searches the library set in the library name field.

A unique ID of the mass spectrum of the target compound in the library is set in the spectrum ID field. When using the NIST library, the NISTID is set. However, if the mass spectrum can be uniquely determined, the CAS registration number may be set in the spectrum ID field without setting the library name field.

FIG. 6B is an explanatory diagram showing an example of peak detection conditions. The peak detection conditions are composed of fields of compound name and peak detection time width. These parameters can be set for each compound.

The compound name field stores the name of the target compound whose peak is to be detected.
In the peak detection time width field, the time width of the peak detection range (holding time range [Tw] described above) is set in units of minutes. The peak detection time is represented by RT±(peak detection range time width/2). For example, if RT=3 minutes and peak detection range time width=0.5 minutes (30 seconds), the peak detection time range is between 2 minutes 45 seconds and 3 minutes 15 seconds.

FIG. 6C is an explanatory diagram showing an example of compound identification conditions. The compound identification conditions are composed of fields of compound name, RT tolerance, I/Q ratio tolerance, and spectral similarity threshold.

The compound name field stores the name of the target compound to be identified.
In the RT tolerance field, the retention time [RT] of the top position of the peak detected from the chromatogram by the mass spectrum extraction unit 12 (the position with the highest intensity between the left end and the right end of the peak) and the quantification condition are set. The allowable range for the difference in retention time [RT] that is used is set in minutes as the RT Tolerance. For example, the RT tolerance is expressed as 0.083 minutes (5 seconds). The identification unit 14 determines that the target compound is detected when the retention time [RT] at the top position of the peak is within the RT tolerance. On the other hand, the identification unit 14 determines that the target compound is not detected when the retention time [RT] of the top position of the peak is not within the RT tolerance.

In the I/Q ratio allowable error field, the I/Q ratio allowable error in the mass spectrum extracted from the peak of the chromatogram by the mass spectrum extraction unit 12 is set in percentage. The I / Q ratio tolerance is the difference between the measured I / Q ratio (measured I / Q ratio) and the I / Q ratio set in the compound information of the quantitative condition setting file (set I / Q ratio) This is the value obtained by calculating the error using the following equation (2). Here, the value obtained by subtracting the set I/Q ratio from the measured I/Q ratio for the set I/Q ratio is calculated as the I/Q ratio error rate (%) by the following equation (3). Then, the identification unit 14 determines whether or not the target compound is detected based on whether or not the I/Q ratio error rate is within the allowable error range.

I/Q ratio error rate (%)=|actually measured I/Q ratio−set I/Q ratio|÷(set I/Q ratio)×100 Equation (3)

For example, if the measured I/Q ratio is "0.6" and the set I/Q ratio is "0.5", the I/Q ratio error rate is |0.6−0.5|/0.5 x100=20%. Then, the identification unit 14 determines that the target compound is detected when the I/Q ratio error rate obtained by the formula (3) is within the I/Q ratio tolerance range of the compound identification conditions. On the other hand, the identification unit 14 determines that the target compound is not detected when the I/Q ratio error rate obtained by Equation (3) does not fall within the I/Q ratio allowable error range.

In the spectral similarity threshold field, a spectral similarity threshold (referred to as a spectral similarity threshold) obtained by comparing an actually measured mass spectrum with a mass spectrum of a compound hit by library search is set. The spectral similarity score is, for example, 0.000 to 1.000, but may be 0 to 999. The spectral similarity has the highest value (1.000), for example, when the mass-to-charge ratio [m/z] completely matches the intensity of the mass spectrum. The identification unit 14 uses the mass spectrum extracted by the mass spectrum extraction unit 12 to perform a pattern search of, for example, mass spectra registered in the spectrum library of NIST, and finds compounds of mass spectra whose spectral similarity is equal to or higher than the spectral similarity threshold. Search for Pattern search is used to detect whether a target compound is contained in a sample component or to detect what compound is contained in a sample component.

Then, the identification unit 14 determines that the target compound is detected when the compound with the highest spectral similarity among the compounds hit by the library search matches the compound set in the quantification condition setting file. However, if a compound set in the quantification condition setting file is included in multiple mass spectra with spectral similarity thresholds or higher, even if it is not the compound with the highest spectral similarity, it will not be a sample component. It may be determined that the target compound is contained. Then, if the spectral similarity is less than the spectral similarity threshold, the identification unit 14 determines that the sample component does not contain the target compound.

In addition, when the mass spectrum of a compound that should not originally be contained in the sample components is detected as the mass spectrum with the highest spectral similarity, it may be determined that such a compound is not detected. In addition, even if a compound is hit by the library search using the spectral similarity threshold, if the hit compound does not include the compound set in the quantification condition setting file, the identification unit 14 does not identify the target compound. It may be determined as detection.

Further, the identification unit 14 does not have to use the pattern search of the actually measured mass spectra in the library search. For example, if the spectral similarity between the library name of the spectrum library and the mass spectrum extracted by the mass spectrum extraction unit 12 with respect to the spectrum of the library specified by the spectrum ID is less than the spectral similarity threshold may determine that the target compound is not detected.

In this way, the identification unit 14 determines that the target compound is detected when three conditions, ie, the RT tolerance, the I/Q ratio tolerance, and the spectrum similarity threshold, which are shown as compound identification conditions, are satisfied. However, the determination may be made based on only one or two conditions selected from the three conditions. As described below, the identification unit 14 according to the first embodiment determines the RT tolerance. The identification unit 14 according to the second embodiment determines RT tolerance and I/Q ratio tolerance. The identification unit 14 according to the third embodiment determines RT tolerance, I/Q ratio tolerance, and spectral similarity threshold.

Detailed information is required for the peak detection parameters used by the identification unit 14 to actually detect mass spectrum peaks and the library search parameters used by the identification unit 14 for library search. . However, since the present invention does not relate to the peak detection method or the library search method, only the minimum parameters necessary for realizing the present invention are listed in the present embodiment.

FIG. 7 is an explanatory diagram showing a display example of the detection result display screen 20. As shown in FIG. The detection result display screen 20 displays the identification result of the identification processing by the identification unit 14 on the display unit 17 .

The detection result display screen 20 includes a TICC display area 21, a compound peak appearance prediction area 22, and a list display area 23 that can be displayed on the display unit 17 as detection results. The TICC display area 21 , compound peak appearance prediction area 22 , and list display area 23 are all displayed on the display unit 17 based on the image data created by the image data creation unit 15 .

The detection result display screen 20 is displayed on the display unit 17 in real time at the same time when the mass spectrometry data processing device 1a analyzes the data. The mass spectrum extraction unit 12 extracts the mass spectrum near the peak of the target compound detected from the chromatogram based on the retention time [RT] read from the quantitative condition setting file stored in the storage unit 11 .

In the TICC display area 21, the TICC obtained by integrating the signal intensity [I] for each retention time [RT] by the mass spectrum extraction unit 12 is displayed.

In the compound peak appearance prediction area 22, mass spectrum peaks extracted from the chromatogram peaks are displayed in a predetermined time width area centered on the retention time [RT] corresponding to the target compound. The mass spectrum peak differs for each target compound. Therefore, the detection result display screen 20 displays a plurality of compound peak appearance prediction regions 22 for each target compound to be identified.

As described above, the retention time [RT] is set for each target compound in the quantitative condition setting file. For example, in FIG. 7, four compound peak appearance prediction regions 22 corresponding to DIBP (diisobutyl phthalate), DBP (dibutyl phthalate), BBP (butyl benzyl phthalate), and DEHP (bis(2-ethylhexyl) phthalate) are collectively displayed together with the retention time [RT] of each compound. The time width of the compound peak appearance prediction region 22 is, for example, 15 seconds before and after the retention time [RT], that is, 30 seconds. Here, an example is shown in which a mass spectrum having a peak in the DIBP compound peak appearance prediction region 22 is displayed. Note that the compound peak appearance prediction region 22 of each compound may be displayed in the order in which the elapsed time from the start of measurement reaches the retention time [RT] of each target compound.

When a mass spectrum including a peak is displayed in the compound peak appearance prediction region 22, the identification unit 14 further performs library search for this mass spectrum according to the quantification conditions read from the quantification condition setting file. At this time, the identification unit 14 identifies the target compound according to any one of RT tolerance, I/Q ratio tolerance, and spectral similarity threshold.

Then, the identification result by the identification unit 14 is displayed with a symbol of ◯ or x in the list display area 23, which is an example of the detection result display area. In the list display area 23, when the identifying unit 14 identifies the compound to be identified, information indicating that the compound to be identified has been identified is displayed. For example, when a DIBP is identified, the DIBP column in the list display area 23 displays a circle symbol indicating that the DIBP has been identified.

Next, a measuring method according to the first embodiment will be described with reference to FIGS. 8 to 10. FIG.
8 and 9 are flowcharts showing an example of main processing of the mass spectrometer 1. FIG.

When the user inputs the quantitative condition setting file , the mass spectrometer 1 starts measurement (S1). Then, the identification unit 14 reads the quantitative conditions from the quantitative condition setting file (S2). At this time, the identification unit 14 acquires the retention time [RT] from the compound information in FIG. 6A and the peak detection time width from the peak detection conditions in FIG. 6B set in the quantification condition setting file as the quantification conditions.

Next, the identification unit 14 calculates peak detection time ranges for all compounds included in the quantification conditions (S3). Then, the display unit 17 displays the detection result display screen 20 (S4). After that, the processing moves to FIG. The peak detection time range calculated in step S3 is supplied to step S10 of FIG.

In FIG. 9, three processes (first sub-process to third sub-process) operate in parallel. For this reason, the fork node 31 representing that the execution of the three processes is started simultaneously is connected to the connector A continued from FIG.

In the first sub-process shown on the left side of FIG. 9, the sample components are measured by the mass spectrometry unit 102 and the measurement results are stored in the storage unit 11 . Then, the mass spectrum extraction unit 12 extracts a mass spectrum from the TICC based on the data read from the storage unit 11, and obtains mass spectrum data of the extracted mass spectrum (S5). The mass spectrum data acquired by the mass spectrum extraction unit 12 is supplied to the chromatogram creation unit 13 in step S7.

After that, the mass spectrum extraction unit 12 determines whether or not the measurement by the mass spectrometry unit 102 has ended (S6). If the measurement has not finished, the process of step S5 is performed again. If the measurement has finished, the process moves to the join node 32 at the bottom of FIG. 9, which indicates waiting until all the other processes finish. . A join node 32 represents combining multiple processes into one.

In the second sub-processing shown in the center of FIG. 9, the chromatogram creating unit 13 creates a chromatogram for display on the display unit 17 based on the mass spectrum data supplied from the mass spectrum extracting unit 12 in step S5. A process is performed (S7).

Image data of the chromatogram created by the chromatogram creating unit 13 is created by the image data creating unit 15, and the chromatogram is displayed on the display unit 17 (S8). At this time, the detection result display screen 20 is displayed on the display unit 17 . After that, the chromatogram generator 13 determines whether or not the measurement by the mass spectrometer 102 has ended (S9). If the measurement has not ended, the process returns to step S7 and the process is performed.

In the third sub-process shown on the right side of FIG. 9, based on the peak detection time range supplied from step S3 in FIG. time) is searched for a target compound (S10). Then, the identification unit 14 determines whether or not there is a compound that satisfies the condition of step S10 (S11). In step S11, if there is no target compound that satisfies this condition (NO in S11), the process proceeds to the process of determining the end of measurement (S16).If there is a target compound (YES in S11), the process proceeds to the first identification process. (S12).

Here, the first identification processing in step S12 will be described.
FIG. 10 is a flow chart showing an example of the first identification process for identifying the target compound based on the retention time [RT] of the quantitative conditions. In the first identification process, the identification unit 14 sets the retention time [RT] of the peak of the chromatogram detected closest to the retention time [RT] set for each compound to be identified as the quantification condition, and the quantification condition. Find the difference from the calculated retention time [RT]. Then, when this difference satisfies the retention time [RT] tolerance set as the quantitative condition, the identification unit 14 identifies the sample component as the compound to be identified.

First, based on the chromatogram supplied from step S7, the identification unit 14 performs peak detection of the chromatogram within the peak detection time range supplied from step S3 of FIG. 8 (S21). Next, the identification unit 14 determines whether a chromatogram peak is detected (S22). If no chromatogram peak is detected (NO in S22), the first identification process is terminated and the process proceeds to step S13 in FIG.

If the chromatogram peak is detected (YES in S22), the identification unit 14 detects the peak detected from the chromatogram supplied from step S21 based on the retention time [RT] of the compound information shown in FIG. 6A. Among them, the peak closest to the retention time [RT] of the quantification condition is searched (S23).

Next, the identification unit 14 determines whether the following formula (4) is satisfied based on the peak closest to the retention time [RT] of the quantification conditions searched in step S23 and the RT tolerance of the compound identification conditions of FIG. 6C (S24), and the process moves to step S13 in FIG.

|Retention time [RT] of quantification conditions−RT of top position of chromatogram peak|≦RT tolerance of quantification conditions Equation (4)

Returning to the description of FIG. 9 again.
After step S12, the identification unit 14 determines whether or not the determination result of formula (4) is valid (S13). If the determination result is valid (OK), the target compound has been detected, and "detected" is displayed as the detection result on the display unit 17 (S14). For example, if it is "detected", a circle symbol is displayed in the column of the detected compound in the list display area 23 of the detection result display screen 20 .

On the other hand, if the determination result is unfair (NG), the target compound was not detected, so "not detected" is displayed on the display unit 17 as the detection result (S15). For example, if it is "non-detected", a cross symbol is displayed in the list display area 23 of the detection result display screen 20. FIG.

After that, the process returns to step S10 and repeats the process. When it is determined in step S11 that there is no target compound, the identification unit 14 determines whether or not the measurement is finished (S16). If more measurements are required (NO in S16), the process returns to step S10 to repeat the process. When all of the first to third sub-processes are finished and the process moves to the join node 32, the main process of the mass spectrometer 1 is finished.

In the first embodiment described above, when the target compound is detected based on the retention time [RT] and RT tolerance in the quantitative condition setting file, The peak detection position of the target compound is indicated, and the detection result is indicated in the list display area 23 . In this way, the mass spectrometry unit 102 performs mass spectrometry and simultaneously performs qualitative analysis in real time. Therefore, analysis results can be obtained without starting separate qualitative analysis software as in the conventional art.

Further, the detection result is immediately displayed on the detection result display screen 20 of the display unit 17 with a symbol of ◯ or x. Therefore, based on the display contents of the detection result display screen 20, the operator can grasp in real time whether or not the target compound has been detected.

[Second embodiment]
Next, an operation example of the mass spectrometer 1 according to the second embodiment of the present invention will be described with reference to FIGS. 11 and 12. FIG. In addition to the first identification process based on the RT tolerance shown in FIG. 10, the mass spectrometer 1 of this embodiment also performs a second identification process based on the I/Q ratio tolerance.

FIG. 11 is a flowchart showing an example of main processing of the mass spectrometer 1 according to the second embodiment.
In the mass spectrometer 1 of the present embodiment, after the main processing shown in FIG. 8 is performed, first to third sub-processings shown in FIG. 11 are performed. Among the steps of the first to third sub-processes, the same step numbers are given to the same parts as the steps shown in FIG. Then, when the determination result of the first identification process in step S13 is OK (YES in S13), the second identification process is performed (S17).

FIG. 12 is a flow chart showing an example of second identification processing for identifying a target compound based on the I/Q ratio error rate. In the second identification process, the identification unit 14 acquires the intensity of the quantified ion and the intensity of the reference ion set for each compound to be identified as the quantification condition based on the spectrum extracted from the peak of the chromatogram. Then, when the ratio of the intensity of the reference ion to the intensity of the quantitation ion is within the range of the error rate obtained in advance, the identification unit 14 identifies the sample component as the compound to be identified.

First, the mass spectrum extraction unit 12 extracts mass spectra from peaks of the chromatogram supplied from step S7 in FIG. 11 (S31). Next, the identification unit 14 acquires the intensity of the quantified ion of the compound obtained from the mass spectrum and the reference ion mass-to-charge ratio [m/z], and calculates the I/Q ratio by the above-described formula (2) (S32 ). As a result, the ratio of the intensity of the reference ion to the intensity of the quantitative ion of the compound actually measured is represented by the I/Q ratio.

Next, the identification unit 14, based on the measured I / Q ratio and the I / Q ratio preset in the quantification condition setting file, calculates the measured I / Q ratio error rate by the above equation (3). Calculate (S33). Next, the identification unit 14 determines whether the actually measured I/Q ratio error rate falls within the I/Q ratio allowable error range set in advance in the compound identification conditions of the quantitative condition setting file (S34), The process moves to step S18 in FIG.

Returning to the description of FIG. 11 again.
After step S17, the identification unit 14 determines whether or not the determination result in step S34 of the second identification process is appropriate (S18). If the determination result is valid (OK), "detected" is displayed as the detection result on the display unit 17 (S14). On the other hand, if the determination result is incorrect (NG), the display unit 17 displays "not detected" as the detection result (S15).
After that, the same processing as that shown in FIG. 9 is performed.

The identification unit 14 according to the second embodiment described above determines that the target compound has been detected when the I/Q ratio error rate is within the I/Q ratio allowable error range. Then, the detection result is displayed in the list display area 23 of the detection result display screen 20 . By continuously performing the first and second identification processes in this way, it is possible to obtain a more reliable result than the conventional analysis method.

Although the mass spectrometer 1 according to the second embodiment continuously performs the first and second identification processes, only the second identification process may be performed. Also, the order of the first identification process and the second identification process may be arbitrary.

[Third embodiment]
Next, an operation example of the mass spectrometer 1 according to the third embodiment of the present invention will be described with reference to FIGS. 13 and 14. FIG. The mass spectrometer 1 of this embodiment performs a third identification process in addition to the first identification process and the second identification process shown in FIG.

FIG. 13 is a flowchart showing an example of main processing of the mass spectrometer 1 according to the third embodiment.
In the mass spectrometer 1 of the present embodiment, after the main processing shown in FIG. 8 is performed, first to third sub-processings shown in FIG. 13 are performed. Among the steps of the first to third sub-processes, the same step numbers are given to the same parts as the steps shown in FIG. Then, when the determination result of the first identification process in step S13 is OK (YES in S13) and the determination result of the second identification process in step S18 is OK (YES in S18), the third identification process is performed. done.

FIG. 14 is a flow chart showing an example of third identification processing for identifying a target compound based on spectral similarities shown as library search results. In this third identification process, the identification unit 14 searches the library based on the spectrum extracted from the chromatogram peak, based on the spectral similarity between the search result and the spectrum extracted from the chromatogram peak. This is a process of identifying that the component contains the compound to be identified.

First, the identification unit 14 accesses the NIST library. Then, the identification unit 14 acquires the mass spectrum extracted by the mass spectrum extraction unit 12, the library name of the NIST spectrum library included in the compound information of the quantification condition setting file, the spectrum similarity threshold of the compound identification condition, and Based on this, mass spectrum library search is executed (S41). Then, the identification unit 14 obtains a mass spectrum searched from the spectrum library based on the spectrum ID and the library name of the spectrum library included in the compound information of the quantitative condition setting file as a library search result. Note that the identification unit 14 may access the library stored in the storage unit 11 to obtain the library search result.

Next, the identification section 14 compares the library search result with the mass spectrum extracted by the mass spectrum extraction section 12 . Then, the identification unit 14 determines whether the mass spectrum having the highest spectral similarity among the mass spectra having the spectral similarity equal to or higher than the spectral similarity threshold matches the spectrum set in the quantitative condition setting file. Determine (S42).

In step S42, if the mass spectrum represented as the library search result in S41 matches the spectrum of the compound set in the quantitative condition setting file, it is determined that the target compound is contained in the sample component. You may Alternatively, in step S42, the library search in step S41 may not be performed, and if the spectral similarity is equal to or higher than the spectral similarity threshold as described above, it may be determined that the target compound is contained in the sample component.

Returning to the description of FIG. 13 again.
After step S19, the identification unit 14 determines whether or not the determination result in step S42 of the third identification process is appropriate (S20). If the determination result is valid (OK), "detected" is displayed as the detection result on the display unit 17 (S14). On the other hand, if the determination result is incorrect (NG), the display unit 17 displays "not detected" as the detection result (S15).
After that, the same processing as that shown in FIG. 9 is performed.

The identification section 14 according to the third embodiment described above compares the mass spectrum of the library search result with the mass spectrum extracted by the mass spectrum extraction section 12 . Then, when the mass spectrum whose spectral similarity is equal to or higher than the spectral similarity threshold matches the spectrum set in the quantitative condition setting file, it is determined that the target compound has been detected. Then, the detection result is displayed in the list display area 23 of the detection result display screen 20 . In this way, by continuously performing the first to third identification processes, it is possible to obtain a more reliable result than the conventional analysis method.

In the mass spectrometer 1 according to the third embodiment, the first to third identification processes are continuously performed, but only the third identification process may be performed. Also, the first and third identification processes may be performed in succession, or the second and third identification processes may be performed in succession. Also, the order of the first to third identification processes may be arbitrary.

The present invention is not limited to the above-described embodiments, and can of course be applied and modified in various other ways without departing from the gist of the present invention described in the claims.
For example, each of the above-described embodiments is a detailed and specific description of the configuration of the apparatus in order to explain the present invention in an easy-to-understand manner, and is not necessarily limited to those having all the configurations described. Further, it is possible to replace part of the configuration of the embodiment described here with the configuration of another embodiment, and furthermore, it is possible to add the configuration of another embodiment to the configuration of one embodiment. It is possible. Moreover, it is also possible to add, delete, or replace a part of the configuration of each embodiment with another configuration.
In addition, the control lines and information lines indicate those considered to be necessary for explanation, and not all the control lines and information lines are necessarily indicated on the product. In practice, it may be considered that almost all configurations are interconnected.

DESCRIPTION OF SYMBOLS 1... Mass spectrometer, 1a... Mass spectrometry data processing apparatus, 10... Input-output control part, 11... Storage part, 12... Mass spectrum extraction part, 13... Chromatogram preparation part, 14... Identification part, 15... Image data preparation Part 16... Operation part 17... Display part 20... Detection result display screen 101... Sample separation part 102... Mass spectrometry part

Claims (5)

A mass spectrometry data processing device for identifying the sample components based on the data obtained by sequentially mass spectrometrically analyzing the sample components separated according to the retention time by a chromatograph,
a chromatogram creation unit that creates a chromatogram corresponding to each mass-to-charge ratio of an integer mass from the data obtained by the mass spectrometry in a preset identification condition time width;
Based on the identification conditions, an identification process for identifying whether the actually measured sample component obtained from the chromatogram is a target compound to be identified is performed.separated by said chromatographan identification unit that is performed in real time according to the timing of mass spectrometry;
an image data creation unit for creating image data for displaying an identification result indicating whether or not the target compound is detected by the identification process;
Based on the image data, After calculation of the peak detection time range of the target compound by the identification unit, peak detection of a spectrum extracted from the chromatogram peak in a region of a predetermined time width centered on the retention time corresponding to the compound to be identified. displaying a first detection result display screen including a predicted compound peak appearance region for each of the target compounds to be identified, which displays a position;
After the display of the first detection result display screen, if the identification unit detects the compound to be identified within a predetermined time span around the retention time corresponding to the target compound, the identification target compound is a display unit for displaying a second detection result display screen including the expected compound peak appearance region of the target compound indicating the peak detection position of the extracted spectrum of the target compound,
The image data created by the image data creation unit is for displaying the first detection result display screen and the second detection result display screen on the display unit.
Mass spectrometry data processor. The identification process includes the retention time of the peak of the chromatogram detected closest to the retention time set for each target compound to be identified as a quantification condition, and the retention time set as the quantification condition. 2. The mass spectrometry data processing apparatus according to claim 1 , wherein the sample component is identified as the target compound to be identified when the difference between and satisfies the retention time tolerance set as the quantification condition. In the identification process, based on the spectrum extracted from the peak of the chromatogram, the intensity of a quantification ion set for each target compound to be identified as a quantification condition and the intensity of a reference ion are obtained, and the intensity of the quantification ion is obtained. 3. The process of identifying the sample component as the target compound to be identified when the ratio of the intensity of the reference ion to the intensity of the reference ion falls within a range of a previously determined error rate. mass spectrometry data processor. The identification process is based on the similarity between a search result of searching a library based on the spectrum extracted from the chromatogram peak and the spectrum extracted from the chromatogram peak, and the sample component is identified as the target of identification. The mass spectrometry data processing device according to claim 1 or 2 , wherein the processing is to identify that the target compound is contained. A mass spectrometry data processing method for identifying the sample components based on the data obtained by sequentially mass spectrometrically analyzing the sample components separated according to the retention time by a chromatograph,
a step of creating a chromatogram corresponding to each mass-to-charge ratio of an integer mass from the data obtained by the mass spectrometry in the time width of a preset identification condition;
Based on the identification conditions, an identification process for identifying whether the actually measured sample component obtained from the chromatogram is a target compound to be identified is performed.separated by said chromatographa step performed in real time in accordance with the timing of mass spectrometry;
a step of creating image data for displaying an identification result indicating the presence or absence of the target compound by the identification process;
Based on the image data, After calculating the peak detection time range of the target compound by the identification process, peak detection of a spectrum extracted from the chromatogram peak in a region of a predetermined time width centered on the retention time corresponding to the compound to be identified. a step of displaying a first detection result display screen including a compound peak appearance predicted region for each of the target compounds to be identified that displays a position;
After the display of the first detection result display screen, if the identification target compound is detected within a predetermined time span around the retention time corresponding to the target compound, the identification target compound is displaying a second detection result display screen including the expected compound peak appearance region of the target compound indicating the peak detection position of the extracted spectrum of the target compound;
The image data created in the step of creating the image data is for displaying the first detection result display screen and the second detection result display screen.
Mass spectrometry data processing method.

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