JP2010071651A - Chromatograph/mass spectrometer - Google Patents

Abstract

<P>PROBLEM TO BE SOLVED: To grasp the data of the chromatogram peak top of a target component in scanning measurements, without fail. <P>SOLUTION: For example, the retention times of the target components are preliminarily calculated by SIM measurements to be stored in a holding time information memory part 33. When an interval is to be measured, measurement starting time, or the like, is set as the measuring parameters of scanning measurement from an input part 36; a scanning starting time operating part 32 uses the delay time of data acquisition, corresponding to the masses of the target components calculated from the measurement starting mass, measurement completing mass, or the like, in addition to the holding time of the target component and the measuring interval to correct the measurement starting time. As a result, the data of the peak top can be grasped, regardless of the masses of the target components, peak heights can be accurately calculated, and the reproducibility of analysis is improved. <P>COPYRIGHT: (C)2010,JPO&INPIT

Description

  The present invention relates to a chromatograph mass spectrometer such as a gas chromatograph mass spectrometer (GC / MS) and a liquid chromatograph mass spectrometer (LC / MS), and more specifically, a predetermined mass (strictly speaking, in a mass spectrometer). The present invention relates to a chromatograph mass spectrometer that performs scan measurement that repeats mass scanning in the range of m / z value.

  In a chromatograph mass spectrometer such as GC / MS, scan measurement and SIM (selected ion monitoring) measurement are known as typical measurement modes. Scan measurement is a technique for acquiring the signal intensity of ions while continuously scanning between two set masses, and is mainly used for acquiring a mass spectrum for the purpose of qualitative analysis. On the other hand, SIM measurement is a method for acquiring only the ion signal intensity of a specific mass or masses, and is mainly used for obtaining a highly sensitive chromatogram for the purpose of quantitative analysis.

  In the SIM measurement, it is necessary to specify the mass of the measurement target in advance, and basically a known substance is the measurement target. On the other hand, since the scan measurement can obtain signal intensity even for a substance whose mass is unknown, it is often used for analysis of a sample whose content is unknown. However, due to the rapid performance improvement of mass spectrometers in recent years, it has become possible to perform sufficiently high-sensitivity measurements even in scan measurement, and unintended substances other than the substances to be measured have been included in the sample. Even in this case, there is an advantage that it can be detected without missing, so that scan measurement is often used for quantitative analysis.

  The main measurement parameters set by the user when performing the scan measurement are a measurement start time Ts, a measurement end time Te, a measurement start mass Ms, a measurement end mass Me, a measurement interval Ti, and the like. FIG. 2 shows the state of mass scanning over time when these parameters are set (see, for example, Patent Document 1). As can be seen from the figure, mass scanning from the measurement start mass Ms to the measurement end mass Me is repeatedly executed from the measurement start time Ts to the measurement end time Te. The repetition period of mass scanning is the measurement interval Ti, and the scanning speed is determined by the measurement interval Ti, the measurement start mass Ms, and the measurement end mass Me.

  For example, in GC / MS, sample components separated in the GC section have a continuous distribution in time, so it is ideal to take continuous data to observe the temporal intensity change of a certain component. Is. In the case of creating a mass chromatogram by repeatedly acquiring ion intensity data for only one mass in SIM measurement, the data acquisition interval is determined by the sampling time interval for sampling the detection signal, so this interval can be considerably shortened. . On the other hand, in the scan measurement, as shown in FIG. 2, the ion intensity data obtained for a certain mass (for example, Mmc in the figure) becomes the time interval of the measurement interval Ti, and the interval is quite wide.

  3 (a) and 4 (a) are diagrams showing a relationship between a virtual chromatogram and a data acquisition point based on a temporally continuous intensity distribution of a certain sample component, and FIG. 3 (b) and FIG. FIG. 4B is a diagram showing a polygonal chromatogram that can be actually created by connecting the respective data acquisition points. In GC / MS, the number of data points in the appearance period of one chromatogram peak is generally about 10 at the most. Therefore, as shown in FIG. 3, there are cases where data of the chromatogram peak top can be collected, and as shown in FIG. 4, only data on a curve out of the chromatogram peak top can be collected.

  The height of the chromatogram peak is originally defined by the maximum signal intensity value, but in the case of the example in FIG. 4, the maximum signal intensity value is missed, so an accurate peak height is required. I can't ask for it. In addition, when performing multiple GC / MS analyzes on the same sample, the position at which data is collected on the chromatogram curve of the same component changes from analysis to analysis, which may impair the reproducibility of repeated analysis. .

  In order to reduce the missed peak top data as described above, it is desirable to make the measurement interval Ti as short as possible. However, the shorter the measurement interval Ti, the shorter the measurement time per m / z value, which is disadvantageous in terms of analysis sensitivity.

JP 2002-25498 A

  The present invention has been made in view of the above problems, and an object of the present invention is to provide a chromatographic mass spectrometer that can reliably capture peak top data of a chromatogram in scan measurement. .

In order to solve the above problems, the present invention is a chromatograph mass spectrometer that introduces sample components separated in a time direction in a chromatograph unit into a mass analyzer and performs mass analysis in a scan measurement mode.
It is characterized by comprising timing determination means for determining the start time of the scan measurement based on the retention time of the target component in the chromatograph section and the measurement interval of the scan measurement repetition.

  The retention time of the target component can be obtained from, for example, a mass chromatogram obtained in advance in the SIM measurement mode under the same chromatographic analysis conditions.

  The measurement interval may be set directly by the user using a measurement condition setting means described later, or may be calculated from another measurement parameter such as a scanning speed. . In particular, the measurement interval consists of a measurement period in which a substantial mass scan is performed and a preparation period in which no substantial mass scan necessary for voltage stabilization is performed, and the time width of the preparation period is within the mass scan range. For example, a measurement interval calculated from another measurement parameter is used.

  Conventionally, the scan measurement start time is generally determined arbitrarily by the user's setting, that is, regardless of other measurement parameters, the retention time of the target component, and the like. On the other hand, in the chromatograph mass spectrometer according to the present invention, the timing determination means uses the retention time of the target component, that is, the time when the peak top of the target component appears on the chromatogram as a reference, and sets the measurement interval to a predetermined value. The timing for starting the scan measurement is determined based on the point in time that goes back by several minutes. In short, the timing of the start of the scan measurement is determined retrospectively so that the peak top data of the target component whose peak appearance time is known can be acquired.

As one aspect of the chromatograph mass spectrometer according to the present invention,
It further comprises measurement condition setting means for setting scan measurement parameters including at least the measurement interval and scan measurement start time, and the timing determination means uses the scan measurement start time set by the measurement condition setting means as a target. It can be set as the structure corrected based on the holding time of a component, and a measurement interval.

  In this configuration, the user sets the measurement interval and the scan measurement start time as scan measurement parameters by the measurement condition setting means, and the timing determination means has a maximum measurement interval period before and after the set measurement start time. Within this range, the measurement start time is adjusted so that the data acquisition point comes at the retention time of the target component. Therefore, since scan measurement is actually started near the measurement start time set by the user, there is little operational discomfort for the user, and data (mass spectrum, mass chromatogram) in the time range intended by the user is collected. can do.

  Further, in the chromatograph mass spectrometer according to the present invention, in order to more accurately capture the peak-top data of the target component, the timing determination means includes the target component during the measurement interval period in addition to the target component retention time and the measurement interval. It is preferable to determine the start time of the scan measurement in consideration of the delay time of data acquisition with respect to the mass of the component.

  That is, since it takes a certain amount of time to scan the mass between two preset masses (measurement start mass and measurement end mass), it depends on where the mass of the target component is located in the mass scan range. Data acquisition timing is different. Therefore, the timing determination means, for example, measurement start mass, measurement end mass, measurement interval, and when there is a preparation period that is not substantially mass scan in the measurement interval, the time width of the preparation period, Based on the mass of the target component, a delay time for data acquisition of the target component during the measurement interval is calculated, and the start time of the scan measurement is determined including this delay time. Thereby, it is possible to capture peak top data almost accurately for any mass target component.

  According to the chromatograph mass spectrometer according to the present invention, it is possible to collect data by reliably capturing the top of the chromatogram peak for a target component having a known retention time in the chromatograph section. For this reason, accuracy in calculating the peak height is improved, and data reproducibility in the case where the same component is analyzed a plurality of times is also improved. In addition, since the maximum peak data can be obtained, the maximum sensitivity can be achieved, and it is also effective for detecting and quantifying trace components.

  When multiple target components exist in one sample, scan measurement can be performed after setting different measurement parameters for each target component separated in the time direction in the chromatograph section. However, also in this case, the optimum measurement start time can be determined for each target component, and the top data of the chromatogram peak of each target component can be acquired.

  A GC / MS according to an embodiment of the present invention will be described with reference to the accompanying drawings. FIG. 1 is a configuration diagram of a main part of the GC / MS according to the present embodiment.

  In the GC unit 1, a carrier gas such as helium is supplied to the column 12 through the sample vaporizing chamber 10 at a substantially constant flow rate. In this state, when a small amount of liquid sample is injected into the sample vaporizing chamber 10 by the injector 11, the sample is vaporized in a short time, and is sent to the column 12 on the carrier gas flow. Various components in the sample are separated in the time direction while passing through the column 12, and the various components sequentially flow out of the column 12 and are introduced into the MS unit 2 as time elapses from the time of sample injection.

  In the MS unit 2, components in the introduced sample gas are ionized by an ion source 20 by, for example, an electron ionization method, and the generated ions are sent to a quadrupole mass filter 21. A voltage obtained by superimposing a DC voltage and a high frequency voltage is applied to each rod electrode of the quadrupole mass filter 21 from the quadrupole drive unit 24, and only ions having a mass (m / z value) corresponding to the voltage are applied. Selectively passes through the quadrupole mass filter 21 and reaches the ion detector 22. The ion detector 22 outputs an ion current corresponding to the number of ions that reached within a unit time as a detection signal, and the A / D converter 23 digitizes the detection signal and sends it to the data processing unit 35.

  The voltage applied from the quadrupole drive unit 24 to the quadrupole mass filter 21 is controlled by the quadrupole control unit 31. That is, the quadrupole control unit 31 applies a voltage to the quadrupole mass filter 21 in an appropriate pattern based on the measurement mode such as the scan measurement mode and the SIM measurement mode and the measurement parameters set for each measurement mode. As described above, a control signal is sent to the quadrupole drive unit 24. The control unit 34 comprehensively controls the operations of the quadrupole control unit 31 and other units. The control unit 34, quadrupole control unit 31, data processing unit 35, and the like are configured with a personal computer 30 provided with an input unit 36 and a display unit 37, and dedicated control / processing installed in the personal computer 30. Control and processing as described later are achieved by software.

  In the GC / MS of this embodiment, the quadrupole control unit 31 uses a scan start time calculation unit (corresponding to the timing determination means in the present invention) 32 as a functional block in order to execute characteristic control / processing described later. In addition, the scan start time calculation unit 32 calculates the measurement start time at the time of scan measurement using the hold time information stored in the hold time information storage unit 33.

  The GC / MS according to the present embodiment is characterized by a control operation for driving the quadrupole mass filter 21 when mass analysis is executed in the scan measurement mode. Next, this control operation will be described with reference to FIGS. 5 and 6 in addition to FIG.

  In order to perform this control operation, the component to be measured (hereinafter referred to as the following) under the same GC separation conditions (the same column, the same gas flow rate, etc.) as when performing the GC / MS analysis in the scan measurement mode. The retention time Tr of the target component) is obtained in advance and stored in the retention time information storage unit 33. A typical method for obtaining the retention time of a component with a known mass (m / z value) with high accuracy is to perform a SIM measurement specifying the mass of the target component, create a mass chromatogram, It is effective to obtain the retention time (retention time) from the peak top position corresponding to the target component appearing on the gram. In the SIM measurement, especially the SIM measurement in which the measurement object is limited to one mass, the ion intensity data can be collected at a much shorter time interval (that is, densely) than the scan measurement. The holding time can be obtained with high accuracy. When it is desired to analyze a plurality of target components in the scan measurement mode, the retention time of each target component is obtained and stored in the retention time information storage unit 33.

  Prior to the execution of analysis specifying the scan measurement mode, the operator (user) inputs and sets analysis conditions from the input unit 36. The analysis conditions include measurement start time Ts, measurement end time Te, measurement start mass Ms, measurement end mass Me, measurement interval Ti, and the like as measurement parameters in the scan measurement mode. As described above, the measurement interval Ti is a repetition period of mass scanning. However, as shown in FIG. 6, the measurement interval Ti is substantially the same as the measurement period Tmes during which mass scanning is performed. And a preparation period Tset during which no mass scan is performed. The preparation period Tset is provided for a certain period of time for the voltage to stabilize when the voltage is lowered from the voltage value corresponding to the measurement end mass Me to the voltage value corresponding to the measurement start mass Ms in the quadrupole drive unit 24. Is required.

  In the description of this embodiment, the time width of the preparation period Tset is constant, but the time width of the preparation period Tset depends on the mass range (difference between the measurement end mass Me and the measurement start mass Ms). In some cases, the time width of the preparation period Tset is variable. When such control is performed, for example, the measurement period Tmes rather than the measurement interval Ti is set as one of the measurement parameters, and the preparation period Tset determined from the measurement end mass Me and the measurement start mass Ms is added to the measurement period Tmes. As a result, the measurement interval Ti is calculated. When the scanning speed is set as one of the measurement parameters, the measurement period Tmes is calculated from the scanning speed, the measurement end mass Me, and the measurement start mass Ms, and the measurement period Tmes and the preparation period Tset are added. As a result, the measurement interval Ti is calculated.

  When the measurement parameter of the scan measurement is set as described above, the scan start time calculation unit 32 in the quadrupole control unit 31 that has received the measurement parameter via the control unit 34 stores the target component retention time from the retention time information storage unit 33. Ttr is read out, and the measurement start time Ts is calculated from the holding time Ttr and the measurement interval Ti. Specifically, as shown in FIG. 5, the time when the top of the chromatogram peak of the target component appears is the holding time Ttr, and data can be acquired only at the time interval of the measurement interval Ti. Adjust the measurement start time so that the top position becomes the data acquisition point.

Assuming that data is acquired at the end of one measurement interval, the scan start time calculation unit 32 may obtain the measurement start time Ts ′ by the following equation (1).
Ts ′ = Ttr−n · Ti (1)
Here, n is an arbitrary integer. FIG. 5 shows the concept of the above equation (1). In other words, the measurement start time Ts ′ is defined as a time that is a predetermined multiple of the measurement interval Ti, that is, a time point that is back by n · Ti, starting from the retention time Ttr of the target component. However, here, since the measurement start time Ts is set by the user as one of the measurement parameters, the value of n is determined so that the above Ts ′ is closest to the measurement start time Ts. As a result, the measurement start time Ts set as the measurement parameter is corrected to the actual measurement start time Ts ′ within the time width of the measurement interval at the maximum before and after the measurement parameter.

Actually, “data is not acquired at the end of one measurement interval”, and the timing at which data is acquired in the measurement interval Ti differs depending on the mass of the measurement target. Therefore, in order to reliably acquire the chromatographic peak top data of the target component, it is necessary to consider the time delay at which the data for the mass of the target component is acquired. As described above, when the measurement interval Ti is considered to be divided into the measurement period Tmes and the preparation period Tset, the time delay Tx within the measurement period for acquiring data for the mass Mmc (Ms ≦ Mmc ≦ Me) is From FIG.
Tx = Tmes × [(Mmc−Ms) / (Me−Ms)] (2)
It is. Therefore, equation (1) takes into account the time delay Tx of equation (2),
Ts ′ = Ttr−n · Ti + Tmes × [(Mmc−Ms) / (Me−Ms)] (3)
It can be.

  In the calculation by the equation (3), the measurement start time Ts ′ is determined in consideration of the delay time corresponding to the mass Mmc of the target component. Therefore, when analyzing any target component, the measurement start time Ts ′ can be determined so as to capture the chromatogram peak top data of the target component. When the measurement start time Ts ′ is determined in this way, the quadrupole control unit 24 uses this and other measurement parameters to determine a voltage application pattern as shown in FIG. Control of the multipole drive unit 24 is executed. As a result, the data processing unit 35 can reliably acquire the chromatogram peak top data of the target component.

  It should be noted that a single set of measurement parameters (Ts, Te, Ms, etc.) is constrained by the limitation that the scan measurement execution periods determined by the measurement start time Ts and the measurement end time Te do not overlap for one GC / MS analysis. It is also possible to set Me, Ti). FIG. 7 shows an example in which scan measurement is performed with an appropriate mass range in which the mass of the target component enters in accordance with the vicinity of the time when two different target components appear. Measurement start time Ts1, measurement end time Te1, measurement start mass Ms1, measurement end mass Me1, and measurement interval Ti1 are set as measurement parameters for one target component, and measurement start time Ts2, as measurement parameters for another target component, Measurement end time Te2, measurement start mass Ms2, measurement end mass Me2, and measurement interval Ti2 are set. Even in such a case, if the retention time of each target component is given, the measurement start time Ts1 ′ () that allows capturing the chromatogram peak top data of each target component based on the retention time and the measurement parameter. Ts1 correction value) and Ts2 ′ (Ts2 correction value) can be obtained.

  In the description of the above embodiment, the actually measured retention time for the target component is used as the target component retention time Ttr. However, the retention of the target component from the retention time Tref of another component serving as an index of the retention time of the target component is used. It is also possible to predict and calculate the time Ttr. This is useful when a sample containing the target component can be analyzed only once (that is, SIM measurement cannot be performed in advance).

For example, when the retention index of the target component is known, if the sample containing n-alkane is analyzed in the SIM measurement mode to obtain an accurate retention time, the target is determined from this retention time and the retention index of the target component. The component retention time Ttr can be calculated. Now, if the peak of the target component in the chromatogram appears between the _{n-C n} alkane peaks and _n-C n _{+ 1} alkane peaks, _{n-C n} peak appearance time of the alkane _{t n, n-C n +} 1 The target component retention index ix is defined by the following equation (4) using the alkane peak appearance time t _{n + 1} and the target component retention time Ttr.
ix = 100 · (Ttr−t _n ) / (t _{n + 1} −t _n ) + n (4)
Thus, if you know the retention index ix pre target component Conversely, using n-C _n peak appearance time of the alkane _{t n, n-C n +} 1 time of appearance alkane peaks t _{n + 1,} the following (5 The retention time Ttr of the target component can be calculated from the equation
Ttr = {(ix / 100) -n}. (T _{n + 1} -t _n ) + t _n (5)

  Of course, a substance other than n-alkane can be used as a reference substance for the retention index. It is also clear that a relative retention ratio or the like can be used instead of the retention index.

  The above embodiment is an example of the present invention, and it is obvious that the present invention is encompassed in the scope of claims of the present application even if appropriate changes, corrections and additions are made within the scope of the present invention. For example, in the above embodiment, the present invention is applied to GC / MS, but it is obvious that the present invention can be applied to LC / MS.

The block diagram of the principal part of GC / MS by one Example of this invention. The figure which shows the mode of mass scanning with the time passage in the case of scan measurement mode. The figure which shows the chromatogram actually created and the data acquisition point when the data of peak top can be caught. The figure which shows the data acquisition point when the data of a peak top cannot be caught, and the chromatogram actually created. The figure which shows the relationship between the chromatogram peak of the target component in GC / MS of a present Example, and a measurement start time. Explanatory drawing of the measurement start time determination method in GC / MS of a present Example. The figure which shows the mode of mass scanning in case a some target component exists in a sample.

Explanation of symbols

DESCRIPTION OF SYMBOLS 1 ... GC part 10 ... Sample vaporization chamber 11 ... Injector 12 ... Column 2 ... MS part 20 ... Ion source 21 ... Quadrupole mass filter 22 ... Ion detector 23 ... A / D converter 24 ... Quadrupole drive part 30 ... Personal computer 31 ... quadrupole control unit 32 ... scan start time calculation unit 33 ... holding time information storage unit 34 ... control unit 35 ... data processing unit 36 ... input unit 37 ... display unit

Claims (3)

In the chromatograph mass spectrometer that introduces the sample components separated in the time direction in the chromatograph section into the mass spectrometer section and performs mass analysis in the scan measurement mode,
A chromatograph mass spectrometer comprising: timing determination means for determining a start time of scan measurement based on a retention time of a target component in a chromatograph section and a measurement interval of scan measurement repetition. The chromatograph mass spectrometer according to claim 1,
A measurement condition setting means for setting a scan measurement parameter including at least the measurement interval and a scan measurement start time;
The timing determination unit corrects the scan measurement start time set by the measurement condition setting unit based on the retention time of the target component and the measurement interval. The chromatograph mass spectrometer according to claim 1 or 2,
The timing determining means determines the start time of scan measurement in consideration of the retention time of the target component and the measurement interval, and also the delay time of data acquisition with respect to the mass of the target component during the measurement interval period. Chromatograph mass spectrometer.

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