JP7077481B2 - Mass spectrometer and mass spectrometry method - Google Patents

Description

The present invention relates to a mass spectrometer and a mass spectrometry method.

When quantifying sample components with a mass spectrometer, focus on the m / z value of ions derived from the target component, and select ion monitoring (SIM: Selected Ion Monitoring) or selective reaction monitoring to measure the change in the amount of ions over time. A measurement method called (SRM: Selected Reaction Monitoring) is generally used.

In these methods, since the control conditions of the apparatus are fixed to the target m / z value, the sensitivity to the target ion is good, but the deviation of the m / z value cannot be directly measured.

It is necessary to measure a sample with a known m / z value and calibrate the device in advance, but changes in temperature and humidity affect the electrode members and electric circuits, and the calibrated m / z value shifts. In some cases.

Therefore, before and after the measurement by SIM or SRM, the sample itself or the component whose m / z value is known is scanned and measured, and it is confirmed that the m / z value does not deviate. Alternatively, during the quantitative measurement, information on the m / z value is obtained by temporally dividing the measurement by SIM or SRM and the scan measurement near the m / z value of the known component. Both methods indirectly try to prove that the m / z value measured by SIM or SRM will not deviate.

For example, Patent Document 1 describes "a method for correcting a deviation in mass accuracy of a quadrupole mass filter using an external calibration substance or a reference compound" by a method called rock mass (here, external calibration). A substance or a reference compound is a component having a known m / z value, and a deviation in mass accuracy means a deviation from the true value of the m / z value (not variation)).

Japanese Patent Publication No. 2014-508937

When measuring by SIM or SRM, the control conditions of the device are fixed to the m / z value of the ions derived from the sample component. Therefore, it is not possible to obtain a voucher that the sample component is correctly measured at the specified m / z value.

In the technique described in Patent Document 1, a method for correcting a deviation in mass accuracy is disclosed, but it is directly determined from the measurement results of SIM or SRM whether or not the measurement can be performed correctly at a specified m / z value. Can't be done. That is, when the device control conditions for the target m / z value change due to changes in temperature and humidity, it is difficult to directly recognize them.

When the device control conditions for the m / z value change, ions that should be able to be measured are missed, resulting in a decrease in sensitivity. Furthermore, there may be situations where the quantitative measurement itself is wasted.

An object of the present invention is to detect a deviation of the m / z value due to a change in control conditions, to provide a voucher for the deviation of the m / z value while maintaining the sensitivity required for quantitative analysis, and to obtain a voucher for the deviation of the m / z value. It is to realize a mass spectrometer and a mass spectrometry method that can compensate for the reduced amount of ions.

In order to achieve the above object, the present invention is configured as follows.

An ionization unit that ionizes sample components, a mass analysis unit that selects the ions supplied by the ionization unit, a detection unit that measures the intensity of the ions selected by the mass analysis unit, the ionization unit, and the mass analysis. In a mass analyzer including a unit and a control unit that controls the operation of the detection unit, the control unit selects m / z values at a plurality of locations near the m / z value derived from the target component. A mass analysis control unit that switches the control conditions of the mass analysis unit, an ion intensity detection unit that detects the ion intensity of the m / z value selected by the mass analysis control unit, and a change in the ion intensity detected by the ion intensity detection unit. Based on the neighborhood pattern calculation unit that calculates the ratio of the ion intensity of the m / z values at the plurality of locations in a state where the component amount is constant, and the neighborhood pattern calculation unit that calculates the neighborhood pattern. It is provided with an ion intensity correction unit for compensating for the insufficient ion intensity measured, and measures the change over time in the ion intensity of the m / z value derived from the target component.

Further, in a mass analysis method in which a sample component is ionized, ionized ions are selected, and the intensity of the selected ions is measured, ions having m / z values at a plurality of locations near the m / z value derived from the target component are used. A neighborhood search step that continuously detects the intensity, a component amount change calculation step that calculates the change in the detected ion intensity, and a plurality of vicinitys of the m / z value derived from the target component in a state where the component amount is constant. It is provided with a neighborhood pattern calculation step for obtaining the ratio of the ion intensity of the m / z value at each location and an ion intensity correction step for compensating for the shortage of the ion intensity measured based on the neighborhood pattern, and the m / z derived from the target component. Measure the change in ionic intensity of the value over time.

Detects m / z value deviations due to changes in control conditions, provides vouchers for m / z value deviations while maintaining the sensitivity required for quantitative analysis, and compensates for the amount of ions reduced due to m / z value deviations. It is possible to realize a mass spectrometer and a mass spectrometry method that can be used.

It is a schematic block diagram of a mass spectrometer. It is explanatory drawing of the calibration of the mass spectrometry part. It is explanatory drawing of the control of a quadrupole mass filter. It is an operation flowchart of a control unit. It is a schematic block diagram of a control part. It is a figure which illustrates the mass spectrum at the time of calibration of a quadrupole mass filter. It is explanatory drawing of the change calculation of the component amount. It is a figure explaining the change of the m / z value and the neighborhood pattern. It is a figure which shows the deviation of m / z value and the calculation example of a score. It is a figure which shows the relationship between the score and the deviation of m / z value. It is a figure which shows the example of the condition setting screen. It is a figure which shows the example of the log output which shows the result of correction. It is explanatory drawing of the neighborhood search by scan measurement. It is explanatory drawing of the change calculation of the component amount by a scan measurement. It is a figure explaining the change of the m / z value and the neighborhood pattern by a scan measurement. It is explanatory drawing of the change calculation of the component amount by a tangent line.

A mode for carrying out the present invention will be described with reference to the drawings. The embodiments of the present invention are not limited to the examples shown here.

(Example 1)
As Example 1, a mass spectrometer and a mass spectrometry method that focus on both ends of the m / z value of an ion derived from a target component in the neighborhood search will be disclosed.

FIG. 1 is a schematic configuration diagram of the mass spectrometer of the first embodiment.

In FIG. 1, the sample supply device 110 supplies sample components to the mass spectrometer 120. For example, a liquid chromatograph, a gas chromatograph, a device for vaporizing components by heating a sample, and the like are sample supply devices. A mechanism for holding a sample in imaging mass spectrometry is also a kind of sample supply device.

The mass spectrometer 120 includes an ionization unit 121, a mass spectrometry unit 122, a detection unit 123, and a control unit 124. The sample component supplied from the sample supply device 110 is ionized by the ionization unit 121, and the mass spectrometry unit 122 selects ions having a predetermined m / z value from the ions supplied from the ionization unit 121, and the detection unit 123. It is measured as an ion intensity in.

The control unit 124 controls the mass spectrometry unit 122 to select a predetermined m / z value according to the instruction from the input / output device 130, and returns the ionic strength data corresponding to the m / z value to the input / output device 130. ..

Here, a method of obtaining an arrangement of m / z value and ionic strength, that is, a mass spectrum while scanning the m / z value in a predetermined range is called scan measurement. Further, it is a quantitative measurement called SIM or SRM to fix the m / z value selected by the mass spectrometer 122 and obtain a change with time of ionic strength, that is, a chromatogram.

FIG. 2 is a diagram illustrating calibration of the mass spectrometer 122.

Generally, in the calibration of the mass spectrometer 122, a sample component having a known m / z value is measured, and the control conditions of the mass spectrometer 122 are adjusted so that the measured value and the known m / z value match. In FIG. 2, the peak obtained by scanning the range of peaks giving M to the sample component having an m / z value of M (for example, M ± 2Da) is the peak 210 before calibration, and the m / z value obtained from the peak 210. Was set to M'.

Here, the peak obtained by adjusting the control value of the mass spectrometer 122 so that the m / z value becomes M is the peak 220 after calibration. Further, the width indicated by the straight line 230 with arrows at both ends is the half-value width of the peak 220 after calibration, that is, the width of the peak at the half-value of the peak height.

At the time of calibration, it is necessary that the supply amount of the sample component having a known m / z value and the efficiency in the ionization unit 121 are constant. When the amount of the sample component to be ionized changes, the ionic strength obtained by the detection unit 123 changes, and the values of M'and M in FIG. 2 cannot be measured correctly.

Next, assuming a case where a quadrupole mass filter is adopted as the mass spectrometer 122, an outline of control will be described.

In the case of a quadrupole mass filter, it consists of a pair of counter electrodes. The voltage Φ (phi) applied to these is given by the following equation (1).

However, in equation (1), Φ is the voltage applied to the quadrupole, U is the DC voltage (DC), V is the maximum value of the AC voltage (RF), cos is a trigonometric function, ω is the angular frequency, and t is the time. Is.

In the formula (1), the control values adjusted by calibration are the DC voltage U and the maximum value V of the AC voltage.

Next, the control of the quadrupole mass filter will be described with reference to FIG. FIG. 3 is a graph showing the relationship between M ₁ , M ₂ , and M ₃ (M ₁ <M ₂ <M ₃ ), which are the m / z values of the calibration points, and RF and DC obtained by calibration.

In FIG. 3, the control unit 124 of the mass spectrometer 120 refers to the line segment (calibration curve) 310 connecting the calibration points, and controls the calibration points M ₁ , M ₂ , and M ₃ by interpolation or extrapolation. Find the point corresponding to the m / z value to be, and determine the RF and DC values. Since the m / z value of the target component for quantification is generally known, the quantification component itself may be used for calibration.

In addition, calibration of the device is the work of adjusting the m / z value of the target peak or the peak shape represented by the full width at half maximum to the target value by adjusting the values of RF and DC. Become.

FIG. 4 is an operation flowchart of the control unit 124, and FIG. 5 is a schematic block diagram of the control unit 124.

Hereinafter, the details of the control operation will be described with reference to FIG. 5 and the like according to the operation flowchart of FIG.

(1) Initial setting step 410
As initial settings, the conditions for quantitative analysis, the conditions for neighborhood search, and the like are set in the input / output device 130 and transferred to the control unit 124. Each processing block in the control unit 124 of FIG. 5 proceeds with processing using the initially set value.

The details of the initial setting are included in the description after the neighborhood search step 420.

Further, FIG. 11 shows an example of a condition setting screen in the display unit of the input device 130. Details will be described after the explanation of the operation flowchart.

(2) Neighborhood search step 420
The neighborhood search replaces the conventional quantitative measurement such as SIM and SRM. The processing is carried out by the mass filter control unit (mass spectrometry control unit) 510 and the ion intensity detection unit 520 of FIG.

Since the mass filter control unit 510 selects two or a plurality of m / z values corresponding to the search points in the vicinity of the m / z value derived from the target component, the control conditions of the mass spectrometric unit 122, which is a mass filter. Are switched sequentially. Further, the mass filter control unit (mass spectrometry control unit) 510 can also scan and measure the search point of the neighborhood search in the range of the m / z value of −0.5 to +0.5 derived from the target component. ..

The ion intensity detection unit 520 detects ions having an m / z value selected by the mass filter control unit 510 from the detection unit 123.

First, the search points and the basic idea in the neighborhood search will be described with reference to FIG.

The neighborhood search is a process for obtaining a change over time in ionic strength with respect to the m / z value in the vicinity thereof, instead of the m / z value of the target component to be measured by the conventional SIM or SRM. Here, an example is shown in which three points including the m / z value of the target component are set as search points. The first embodiment is a method of paying attention to both ends of a plurality of search points, and the search points corresponding to the m / z values are not always required.

FIG. 6 is a diagram illustrating a mass spectrum 610 at the time of calibration of a quadrupole mass filter. This is obtained by scanning and measuring before and after the m / z value M of the target component, and is shown in FIG. 6 focusing on the vicinity of the peak top.

From the mass spectrum 610, search for three m / z values of M-Δ corresponding to the point 620 on the left side of the peak top 630, M of the peak top 630, and M + Δ corresponding to the point 640 on the right side of the peak top 630. Set as a point.

That is, as a neighborhood search, the change with time of the ionic strength corresponding to the three points of M−Δ, M, and M + Δ is obtained. Here, Δ (for example, 0.1 Da) and the search point are initially set in the vicinity of the peak top of the mass spectrum with reference to the peak width and the like. The optimum value of Δ depends on the peak shape, such as setting a large value for Δ if the width of the peak at the time of calibration is wide and a small value if it is narrow. Of the m / z values in the vicinity of the m / z value (search point) derived from the target component, the m / z values located at both ends of the m / z value derived from the target component are ideally peaks. It is desirable that the m / z value is a few percent lower than the top and is at least half the peak value.

For example, in the former example, at the peak with a half width of 0.7, the ionic strength of M is 100%, and the ionic strength of m / z value (M−Δ) is 98.6%. adopt. Further, in the latter example, a Δ value of 0.5 Da at which the ionic strength of the m / z value M−Δ is 50% at the peak of the half width of 1.0 is adopted.

In the neighborhood search, the process of sequentially obtaining the ionic strength of a set of search points (M−Δ, M, M + Δ in this example) specified in advance in the initial setting is set as one cycle, and the process is repeated.

At the time of calibration, the amount of components is basically constant, but when measuring an actual sample, the amount of components changes.

Therefore, an example in which the amount of the component increases during the measurement of each point in one cycle is shown at points 660 (P ₁ ), 670 (P ₂ ), and 680 (P ₃ ) in FIG. Each point is connected by a line segment 690 to clarify the corresponding cycle. Here, P _j indicates a measurement point, and j is the number of the search point in the cycle and the measurement order in the cycle.

As a reference, the mass spectrum obtained by scanning measurement in a situation where the amount of components is increasing is shown by a dotted line 650 (actually, scanning measurement is not performed). It can be seen that the mass spectrum 650 is higher on the right side than the mass spectrum 610 due to the rising component amount, and the ionic strength of P ₃ is higher than that of P ₁ . That is, if the amount of components is not constant, the deviation of the m / z value of the device cannot be detected correctly.

Here, the amount of components when the mass spectrum 610 is obtained is Q0, and the ionic strength of the peak top 630 is IB. Further, for each search point j in the mass spectrum 610, the ionic strength ratio with the peak top is R _j .

For example, the ionic strength ratio of search point 1 (ionic strength of point 620 / IB) is R ₁ , the ionic strength ratio of search point 2 (ionic strength of point 630 / IB) is R ₂ (= 1), and the search point 3 Ionic strength ratio ₍ ion strength at point 640 / IB) is R3. Assuming that the component amount is Q _j and the ionic strength ratio is I _j at each search point P _j , the following equation (2) holds on the premise that the ionic strength is proportional to the component amount.

However, in the formula (2), Q0 is the component amount at the time of calibration, IB is the ionic strength of the peak top at the time of calibration, the subscript j is the number of the search point, and R _j is the ion intensity ratio (component amount) of the search point j. The peak top ratio of the ionic strength at a constant level), I _j is the ionic strength of the search point j, and Q _j is the component amount of the search point j.

Here, R _j can be obtained at the time of calibration, and is registered so that it can be referred to in a later process in the initial setting. When the m / _z value of the device deviates, the value of Rj also changes according to the deviation. In that case, since (I _j / Q _j ) and R _j are proportional, it is necessary that the number of search points is sufficient and the peak top is _{included .} R _j can be recalculated.

(3) Change calculation step 430 of component amount
Step 430, which is a process of calculating the change in the amount of components from the ionic strength of each search point obtained in the neighborhood search cycle, will be described. This is carried out in the change calculation unit 530 of the component amount in FIG. The component amount change calculation unit 530 calculates the ion intensity change detected by the ion intensity detection unit 520. The details will be described with reference to FIG. 7. The component amount change calculation unit 530 calculates the change in ionic strength by a plurality of cycles, and calculates the change in the component amount by a quadratic expression or the like from the cycles before and after.

FIG. 7 is an explanatory diagram of the change calculation of the component amount, and is a diagram showing a state in which the neighborhood search of three points in one cycle is continuously performed. The horizontal axis of FIG. 7 is time and the vertical axis is ionic strength, and the measurement points in one cycle are connected by a straight line. Further, the dotted lines 710, 720, and 730 indicate changes with time of the search points 1, 2, and 3, respectively. In addition, numbers from 1 were given to each cycle in the order of measurement, and they were described as C ₁ to C ₅ .

In the first embodiment of the present invention, the deviation of the m / z value of the apparatus is detected, and in the example shown in FIG. 7, the peak top is shifted from P ₂ to the P ₁ side for explanation. ..

Since the above-mentioned ion intensity ratio _Rj is obtained under a constant condition for the amount of components, it indicates the measurement efficiency of ions at each search point, that is, the m / z value. When the m / z value of the device is deviated, the value of R _j also changes according to the amount of deviation, but the value of R _j is larger at the search point closer to the m / z value of the deviated peak top. Considering that the value of _Rj is maintained in a series of cycles, it can be said that the search point that measured the largest number of ions in a certain time domain is the closest to the peak top.

For example, in FIG. 7, considering the area given by the dotted lines 710, 720, and 730, it is obvious that the order is P ₂ , P ₁ , and P ₃ , where P ₂ is the closest to the peak top.

Here, if R _j is the measurement efficiency of ions at the m / z value, the ratio of the area A _j and the ratio of R _j in the same time range at each search point are the same. Focusing on this, the method of Example 1 is to obtain R _j from the area A _j .

As mentioned above, the area cannot be determined by the ionic strength of each search point. Here, the function showing the change in ionic strength is obtained in the time range for each cycle, and the area is obtained from the integrated value.

For example, focusing on the k-th cycle (C _k ), the change in the amount of ions at the search point j also focuses on each point in the previous and next cycles (T _{j, k-1,} I _{j, k-1} ). A quadratic equation can be obtained from the three points (T _{j, k,} I _{j, k} ) and (T _{j, k + 1,} I _{j, k + 1} ). Here, T _{j and k} are the searched time, and I _{j and k} are the ionic strength.

For the quadratic equation obtained for each search point j in this way, the integral value in the time interval of C _k is obtained.

Next, an example of the quadratic equation (3) showing the change of the search point j in the kth cycle is shown.

However, in the equation (3), the subscript j is the search point number, the subscript k is the cycle number, T _{j and k} are the time at the search point j cycle k, and I _{j and k} are the search point j cycle k. Ionic strength, t is time, and f (j, k, t) is a function indicating the ionic strength at the search point j, cycle k, and time t.

Here, Lagrange interpolation is adopted and a quadratic equation is used as an example, but the use of a linear equation is also conceivable. That is, the points before and after are connected by a straight line (linear equation) to obtain a function f (j, k, t) indicating the change in ionic strength. Further, other interpolation methods may be adopted.

For the function f (j, k, t), let A _j be the area in the time range of cycle k. This _Aj is obtained by, for example, the equation (4).

However, in the equation (4), t _Ckmax is the maximum value in the time range of the cycle k, t _Ckmin is the minimum value in the time range of the cycle k, and A _j is the area corresponding to the search point j (of the cycle k).

The ratio of the area A _j thus obtained corresponds to the ratio of R _j . For example, when there are three search points, A ₁ : A ₂ : A ₃ = R ₁ : R ₂ : R ₃ . Further, when the m / z value of the apparatus deviates, R _j indicates the ionic strength ratio at each search point.

When the ionic strength value is small, the area ratio is unstable, and when the ionic strength increases, it approaches the true value. Therefore, the values of _Aj in a plurality of cycles are sequentially added to _Sj and used in the subsequent neighborhood pattern calculation 450. S _j is an integrated value of the area A _j .

(4) Neighborhood pattern confirmation determination step 440
In step 440, it is determined whether or not the integrated value _Sj of the area _Aj obtained in the change calculation step 430 of the component amount is stable.

For example, when the total value of all the integrated values S _j exceeds the threshold value for determining the neighborhood pattern, it is considered that the neighborhood pattern is stable and it is determined as Y, and the process proceeds to the ion intensity correction step 460. If the threshold value for the neighborhood pattern determination determination is not exceeded in the neighborhood pattern determination determination step 440, the neighborhood pattern is regarded as unstable and determined to be N, and the process proceeds to the neighborhood pattern calculation step 450.

Alternatively, instead of the integrated value S _j , the integrated value of the ionic strength I _j can be used. Further, a method of obtaining the absolute value of the difference between S _{j of the cycle and S j obtained} in the previous cycle for each search point and determining the total value is equal to or less than the threshold value can be considered.

(5) Neighborhood pattern calculation step 450
The neighborhood pattern calculation step 450 is performed by the neighborhood pattern calculation unit 540 in FIG.

In the neighborhood pattern calculation step 450, the neighborhood pattern calculation unit 540 calculates the neighborhood pattern, which is the ratio thereof, based on the integrated value _Sj of the area Aj at the search point _j obtained by the change calculation unit 530 of the component amount. Alternatively, the neighborhood pattern calculation unit 540 obtains the ratio of the ionic strength of the m / z value in the vicinity (m / z values at a plurality of locations near the m / z value derived from the target component) in a state where the component amount is constant. , Calculate the neighborhood pattern. Further, the neighborhood pattern calculation unit 540 can also set the ionic strength per unit component amount as the neighborhood pattern from the change in the component amount calculated by the quadratic equation. Further, the score is obtained from the neighborhood pattern, and the deviation of the corresponding Rj and m / _z values is obtained.

For the sake of simplicity, the case where the neighborhood search has two points will be described with reference to FIG.

FIG. 8 is a graph showing the relationship between the deviation of the m / z value of the quadrupole mass filter and the ionic strength, and is a diagram for explaining the change between the m / z value and the neighborhood pattern.

In FIG. 8, the mass spectrum 810 with the m / z value M immediately after calibration, the mass spectrum 820 with the m / z value deviated by 0.05, and the mass spectrum 830 with the m / z value deviated by 0.10 are searched in the vicinity. The two obtained points (point 840 and point 850) were plotted and connected by a straight line. In this way, as the deviation of the m / z value increases, the difference in ionic strength between the two points also increases.

That is, when the shape of the mass spectrum near the peak top is stable, the deviation of the m / z value can be obtained from the neighborhood pattern. In particular, it is possible to focus on both ends of the neighborhood pattern and associate the score obtained from the ratio with the deviation of the m / z value.

The shape of the mass spectrum is determined when the quadrupole mass filter is calibrated. Therefore, it is possible to calculate the relationship between the difference in the neighborhood pattern and the deviation of the m / z value at the time of calibration.

FIG. 9 is a diagram showing a deviation of the m / z value and a calculation example of the score. When the peak of the mass spectrum has a half width of 0.7, the score with respect to the deviation of the m / z value (m / z Error) 910 is shown. It is a table exemplifying the calculation method of.

In FIG. 9, in the ionic strength (I: Ion Integrity) 920, the upper row 1 is the search point 1 having an m / z value of M-0.05, and the lower row 2 is the search point 2 having an m / z value of M + 0.05. It shows the value of the ionic strength with respect to the deviation of each m / z value. For the sake of explanation, the value standardized with the maximum value of ionic strength as 100 is described.

Here, when the deviation of the m / z value is 0.00, 0.05, 0.10, it corresponds to the mass spectra 810, 820, and 830 in FIG. Such a numerical value can be obtained from the mass spectrum actually measured at the time of calibration. Alternatively, the relationship between the m / z value and the ionic strength can be determined by applying the Gaussian function obtained from the full width at half maximum.

Further, as shown in FIG. 8, by assuming a mass spectrum in which the m / z value is deviated, the ratio of the m / z value deviation and the ionic strength of each point obtained by the neighborhood search can be obtained.

In FIG. 9, the ionic strength ratio (R: Ion Integrity Ratio) 930 is a numerical value obtained by normalizing the ionic strength value at the maximum intensity (100 in this case). Further, the expected measurement ratio (R') 940 of the ionic strength was standardized with the larger one as ₁ and the value of _R'max -R'1 as the difference (Dif), paying attention to the ionic strength of the search points at both ends. Since this example has two points, the max of R'is 2. Further, the difference (Dif) is multiplied by 1000 to obtain a score (Score) of 950.

In FIG. 9, R'is a ratio that can be calculated from the measured value, and it is shown that the deviation of the m / z value and R _j can be determined from the score obtained from the ratio.

FIG. 10 shows the relationship between the score and the deviation of the m / z value obtained in this way. The horizontal axis of FIG. 10 is the score (Score) in FIG. 9, and the vertical axis is the deviation of the m / z value (m / z Error). In addition, the line segment 1010 is an interpolated or extrapolated plot of each. FIG. 10 showing the graph thus obtained and created shows the relationship between the score and the deviation of the m / z value in the half width of 0.7.

To summarize here, in the initial setting, the deviation between the score and the m / _z value shown in FIG. 9, and the relationship between Rj are registered. Furthermore, by calculating the score from the ionic strength ratios ( _{R'1 and R'max )} at both ends obtained by the neighborhood pattern calculation, the deviation of the _Rj and m / z values registered in the initial settings is determined, which will be described later. It is referred to in the ion intensity correction step 460 and the m / z value correction step 470. Further, S _j is returned to the initial value before integration.

In this example, the case where the value is shifted to the high m / z value side is mentioned, but of course, the calculation can be performed even on the low m / z value side. Further, if the peak top portion for neighborhood search is symmetrical, only one side can be calculated. By reversing the sign of the score, it is possible to determine which side is deviated.

(6) Ionic strength correction step 460
Subsequently, the ionic strength correction step 460 will be described. This corresponds to the processing in the ion intensity correction unit 550 in FIG. The ionic strength correction unit 550 compensates for the lack of ionic strength measured based on the neighborhood pattern calculated by the neighborhood pattern calculation unit 540.

Here, a method of correcting the ionic strength measured based on the value of the ionic strength ratio _Rj will be described.

The original ionic strength with respect to the search point j can be obtained by I _j / R _j . That is, the total ionic strength in the cycle can be expressed as the total of all search points, Σ (I _j / R _j ). This value corresponds to the ionic strength of one point on the chromatogram of SIM or SRM in a general quantitative measurement.

The value of each R _j is set as an initialization value in the initial setting step 410, and is updated in the neighborhood pattern calculation step 450. Further, when the m / z value correction is applied, it is returned to the initial value.

(7) m / z value correction step 470
The m / z value correction step 470 is carried out by the m / z value correction unit 560 in FIG.

In the m / z value correction step 470, the m / z value is corrected based on the deviation of the m / z value obtained in the neighborhood pattern calculation step 450. That is, the control conditions of the mass spectrometry control unit 510 are modified based on the neighborhood pattern obtained in the neighborhood pattern calculation step 450. If the neighborhood pattern has not been calculated, the m / z value correction is not performed.

Specifically, from the next measurement, according to the relationship between the m / z value obtained by calibration as shown in FIG. 3 and RF and DC shown in FIG. 3, the shifted m / z that will correspond to the peak top. The RF and DC values corresponding to the values are output from the input / output device 130. Further, for the correction of the m / z value, it is conceivable to set a threshold value according to the specifications such as the mass accuracy of the quadrupole mass filter.

When the deviation of the m / z value is corrected, the value of the ion intensity ratio Rj referred to in the ion intensity correction step 460 (processing by the ion intensity correction unit 550) is returned to the value immediately after calibration without the deviation of the m / _z value. ..

(8) End determination step 480
Although the operation flowchart of FIG. 4 has the end determination step 480, the first embodiment of the present invention corresponds to the deviation of the m / z value in the quantitative measurement of the target component, and the effect is that the peak shape does not change significantly. For example, it can be continued as long as a series of quantitative measurements continues. When the quadrupole mass filter is newly calibrated and the initial setting step 410 is performed, the process is substantially completed.

The first embodiment of the present invention has been described above according to the operation flowchart. In the first embodiment, the condition setting screen (display screen of the input / output device 130) used in the initial setting step 410 will be described with reference to FIG. FIG. 11 is a diagram showing an example of a condition setting screen. In the example shown in FIG. 11, the target component for quantitative measurement is limited to one for the sake of explanation. On the actual condition setting screen, applications such as setting conditions for each of a plurality of target components can be considered.

In FIG. 11, the condition setting screen is roughly classified into Target 1110 that defines the mass spectrum of the target component, Search 1120 that defines the conditions for neighborhood search, and Direction 1130 that defines the conditions for m / z value correction. The meaning of each parameter will be described in detail.

Target 1110 indicates a display area for defining the target component for quantification, and Top 1111 is the m / z value of the peak top of the target component. Further, Wide 1112 is the half width at the peak of the mass spectrum of the target component, and Dwell Time 1113 is the uptake time of the ionic strength of the target component, which gives a value of one point in the chromatogram when performing quantitative processing.

The Search 1120 indicates a region for setting the neighborhood search condition, the Point Number 1121 is the score of the search point of the neighborhood search, and the Dwell Time / Point Number is the capture time of one point of the neighborhood search. Further, Delta1122 is an interval of m / z values of search points. Further, Threshold 1123 is a threshold value for determining the neighborhood pattern, and in Example 1, when the total value of all S _js exceeds this value, it is considered to be stable.

Direction 1130 indicates an area for setting a correction condition for the m / z value. Further, Step 1131 indicates a step of m / z value correction, and when the deviation of the m / z value becomes greater than or equal to this value, the correction is performed. Further, Maximum1132 is the maximum value of m / z value correction, and is a threshold value for which any further correction is treated as an error with respect to the m / z value immediately after calibration.

The relationship between the Score 950, the m / _z Error 910, and the ionic strength ratio Rj shown in FIG. 9 is obtained from the values such as Wide and Delta set under the conditions shown in FIG. As the mass spectrum used here, the one obtained by calibration of the quadrupole mass filter can be used. When the peak shape of the mass spectrum is substituted by the Gaussian function, the standard deviation σ corresponding to the peak of the half width W and the Gaussian function at that time are the following equations (5) and (6). Can be expressed in.

However, in equations (5) and (6), σ is the standard deviation, W is the half-value width, ln is the natural logarithm, x is the m / z value of the search point, y is the ion intensity, and M is the target component m /. The z value and E are the deviations of the m / z value, π is the pi, and e is the Napier number.

If the ionic strength y is obtained from the above equations (5) and (6) and standardized with the maximum value set to 100, a value corresponding to the ionic strength (I: Ion Integrity) 920 shown in FIG. 9 can be obtained. can.

In the initial setting step 410 shown in FIG. 4, the input set by the screen shown in FIG. 11 is received, and for example, the mass spectrum 610 and the search point in FIG. 6 are displayed, and the simulation result as shown in FIG. 8 is displayed. Therefore, the parameters can be set more effectively.

Further, FIG. 12 is a diagram showing an example of log output showing the status of correction.

In FIG. 12, the first line 1210 shows the title of the log, and the second line 1220 shows the m / z value of the target component. The third line 1230 indicates the log item, and means the deviation of the log date / time, the score, the m / z value, and the m / z value in order from the left. The fourth line below 1240 indicates the substance of the log.

In the example shown in FIG. 12, the m / z value specified by Step in FIG. 11 is set on 2018/09/13 from the situation where the m / z value 693.10 of the target component is not deviated from 2018/09/01. Since the score 55 corresponding to the deviation of 0.05 was exceeded, the target m / z value was corrected to 693.10 from 693.15. From the situation of 2018/09/18 with almost no error, it is corrected because it deviates to the low m / z value side in the opposite direction on 2018/09/25. When corrections are made, an asterisk is added next to the score to identify them.

Since the first embodiment of the present invention is configured as described above, it detects the deviation of the m / z value due to the change of the control condition, maintains the sensitivity required for quantitative analysis, and with respect to the deviation of the m / z value. It is possible to realize a mass spectrometer and a mass spectrometry method that can provide a voucher and compensate for the amount of ions reduced due to the deviation of the m / z value.

Further, according to the first embodiment, it is possible to realize a mass spectrometer and a mass spectrometry method that can automatically correct the deviation of the m / z value.

(Example 2)
Next, Example 2 of the present invention will be described.

The second embodiment is an example of scanning and measuring the vicinity of the peak top in the neighborhood search. The first embodiment can be applied by paying attention to both ends of the scan measurement. Here, it is assumed that the search point corresponding to the peak top is included in the scan measurement, and a method of obtaining the deviation of the Rj and m / _z values from the mass spectrum obtained by the scan measurement will be described.

The schematic configuration and operation flowchart of the mass spectrometer in the second embodiment are the same as those in the first embodiment. Here, the difference between the first embodiment and the second embodiment will be mainly described.

(1) Initial setting step 410
The same initial settings as in Example 1 are carried out. However, in the second embodiment, in the condition setting screen shown in FIG. 11, the m / z value interval Delta (Δ) is read as the difference between the m / z values of the start point and the end point of the scan measurement used for the search.

(2) Neighborhood search step 420
FIG. 13 shows the concept of the search point of the neighborhood search. FIG. 13 is an explanatory diagram of neighborhood search by scan measurement.

In FIG. 13, when the mass spectrum 1310 in which the amount of components at the time of calibration can be obtained by scanning is measured from the m / z value M−Δ / 2 to M + Δ / 2 of the target component, ideally from the point 1320. A mass spectrum of 1340 up to point 1330 can be obtained. The search range is from this scan range M−Δ / 2 to M + Δ / 2.

Further, the score of the search point is the one specified in the initial setting, and the acquisition time is the same as the designated capture time (Dwell Time) divided by the score. When the number of search points (Point Number) is as small as 2 or 3, it can be regarded as equivalent to that of the first embodiment, but here, it is assumed that a larger value is set. For example, when Δ is 0.2, the score is 200, and the Dwell Time is 100 ms, 500 μs per point, and the m / z value step of each search point is 0.001 (0.2 / 200) Da.

In addition, one scan measurement is regarded as one cycle, and it is repeated. Further, as in the first embodiment, in the mass spectrum 1350 obtained when the amount of components increases, the mass spectrum 1380 from the point 1360 to the point 1370 is obtained in the neighborhood search. Here, P ₁ is the first search point and P _max is the last search point. In the above example, max is 200. Here, let I _j be the ionic strength of the search point j.

In the case of Example 2, since the measurement time per point is short, the ionic strengths of the mass spectra 1340 and 1380 have large variations. Therefore, the mass spectra 1340 and 1380 may be replaced with an approximate expression such as a quadratic function obtained by regression analysis or the like.

In Example 2, the ionic strength ratio _Rj can be calculated as in Example 1. Assuming that the ionic strength of the peak top of the mass spectrum 1340 is IB, the amount of the obtained component is C0, and the ionic strength ratio with the peak top is Rj for each search point _j of the mass spectrum 1340, the formula of Example 1 is used. (2) can be obtained. That is, the basic idea of the first embodiment can be applied to the second embodiment as well.

(3) Change calculation step 430 of component amount
The change calculation step 430 of the component amount in Example 2 will be described with reference to FIG.

FIG. 14 is an explanatory diagram of calculation of change in the amount of components by scan measurement.

In FIG. 14, P ₁ to P _max of each cycle are the results of the neighborhood search. Further, the dotted line 1410 shows the change with time of the search point 1 (P ₁ ), and the dotted line 1420 shows the change with time of the last search point (P _max ).

In the first embodiment, the temporal changes of P ₁ and P _max at both ends of the search point are interpolated by a quadratic equation or the like, and the areas A ₁ and A _max are sequentially added to S ₁ and S _max , and later. It is used for neighborhood pattern calculation.

In the second embodiment, a method focusing on the dotted line 1430 having the maximum area value is provided. Here, the maximum area value means that the value of the ionic strength ratio Rj becomes the maximum ( ₌ 1), that is, the point corresponding to the m / z value corresponding to the beak top when the component amount is constant. It is nothing but a tied thing. That is, the dotted line 1430 shows the change in the amount of components. Further, since the contact point between the scan measurement result and the dotted line 1430 in a series of cycles corresponds to the m / z value of the target component at the time of measurement, the deviation of the m / z value can be detected. Further, by obtaining R _j from the change in the component amount Q _j and the ionic strength I _j of the mass spectrum, the ionic strength can be corrected.

FIG. 15 is a diagram illustrating changes in the m / z value and the neighborhood pattern by scan measurement for reference. Comparing the example shown in FIG. 8 with the example shown in FIG. 15, it can be seen that the example shown in FIG. 15 captures the relationship between the m / z value and the ionic strength at a higher density. In the case of scan measurement, since the measurement time per point is shortened, there is a feature that the variation in ionic strength becomes large.

Next, a method of obtaining a change in the amount of the component corresponding to the dotted line 1430 by the tangent line will be described with reference to FIG.

FIG. 16 is an explanatory diagram of the calculation of the change in the amount of components due to the tangent line. The change calculation unit 530 of the component amount obtains the change of the component amount by the tangent line circumscribing the mass spectrum by the scan measurement.

FIG. 16 shows the change in the amount of components in cycle k by two tangents 1610 and 1620. That is, the tangent line 1610 tangent to the mass spectrum of cycle k-1 (C _k-1 ) and cycle k (C _k ) (mass spectrum measured by scan measurement), and the tangent to the mass spectrum of cycle k and cycle k + 1 (C _{k + 1} ). Draw tangents 1620 to obtain their intersections 1630.

In this way, as the cycle progresses, the line segment connecting the intersections of the close battles of the spectrum can be determined. It corresponds to the dotted line 1430 in FIG. 14, that is, the change in the component amount _Qj .

Here, the ionic strength I _j / Q _j of the mass spectrum becomes the ionic strength under the condition that the amount of components is constant, and the ionic strength ratio R _j with the peak top as 1 can be obtained.

It is considered that the value of _Rj obtained in this process is unstable. Therefore, instead of A _j in Example 1, the value obtained by multiplying the value of I _j / Q _j obtained in each cycle by the ionic strength at the intersection in that cycle is _taken as the weight. The value of A _j in a plurality of cycles is sequentially added to S _j and used in the later neighborhood pattern calculation.

Although the method of obtaining the tangent line is shown here, for example, in cycle k, a quadratic function circumscribing the mass spectrum (mass spectrum measured by scan) of cycle k-1, cycle k, and cycle k + 1 may be adopted. A quadratic function is assumed with three points as the first candidates that give the maximum value of the mass spectrum corresponding to the cycle k-1, the cycle k, and the cycle k + 1. If it enters within the peak of the mass spectrum in the same cycle and exits from another location, a point in the middle of those points is used as a new contact candidate, and finally a quadratic equation that contacts the mass spectrum of 3 cycles. Ask for.

(4) Neighborhood pattern confirmation determination step 440
In the neighborhood pattern determination determination step 440, it is determined whether or not the integrated value _Sj obtained in the component amount change calculation step 430 in Example 2 is stable.

For example, if the total value of all the integrated values S _j exceeds the threshold value of the neighborhood pattern determination determination step 440, it is considered that the neighborhood pattern is stable, Y (Yes), and if not, N (No). Is determined.

Alternatively, instead of the integrated value S _j , the integrated value of the ionic strength I _j can be used. Further, a method of obtaining the absolute value of the difference between S _{j of the cycle and S j obtained} in the previous cycle for each search point and determining the total value is equal to or less than the threshold value can be considered.

(5) Neighborhood pattern calculation step 450
In the neighborhood pattern calculation step 450, for S _j obtained by the calculation of the change in the amount of components, the value rated with the maximum value of 1 is obtained and used as R _j . Further, the m / z value corresponding to the value of j corresponding to the maximum value is the current m / z value, and the deviation from the m / z value of the target component can be obtained. Further, R _j can be used in the ionic strength correction step 460, and the deviation of the m / z value is used in the m / z value correction step 470.

Here, the value of S _j is cleared.

(6) Ionic strength correction step 460
The ionic strength correction step 460 is performed in the same manner as in Example 1. The ionic strength _Ij of each point used after the correction may be a value before being approximated by a quadratic equation or the like.

(7) m / z value correction step 470
The m / z value correction step 470 is the same as that of the first embodiment. When the m / z value is corrected, Rj referred to in the ion intensity correction step 460 is returned to the value immediately after calibration in which the m / _z value is not deviated.

(8) End determination step 480
The end determination step 480 is the same as that of the first embodiment.

As described above, the example in which the scan measurement is adopted for the neighborhood search of the m / z value M of the target component is shown as Example 2.

In Example 2, the same effect as in Example 1 can be obtained.

(Example 3)
Next, Example 3 of the present invention will be described.

Example 3 is another method of Example 2 in which the vicinity of the peak top is scanned and measured in the neighborhood search.

(1) Initial setting step 410
It is the same as Example 2.

(2) Neighborhood search step 420
It is the same as Example 2.

(3) Change calculation step 430 of component amount
As shown in Example 1, the area ratio of each cycle corresponds to the ratio of _Rj . Therefore, also in the third embodiment, the area A _j and the integrated value S _j of A _j in a plurality of cycles are obtained for each search point j in the same manner as in the first embodiment. Here, the m / z value corresponding to j that maximizes S _j corresponds to the beak top at that time. Further, S _j corresponds to R _j .

(4) Neighborhood pattern confirmation determination step 440
In the neighborhood pattern determination determination step 440, it is determined whether or not the integrated value _Sj of the area _Aj obtained in the change calculation step 430 of the component amount is stable.

For example, if the total value of all the integrated values S _j exceeds the threshold value in the neighborhood pattern determination determination step 440, it is determined that the neighborhood pattern is stable and Y (Yes), otherwise it is determined as N (No). do.

Alternatively, instead of the integrated value S _j , the integrated value of the ionic strength I _j can be used. Further, a method of obtaining the absolute value of the difference between S _{j of the cycle and S j obtained} in the previous cycle for each search point and determining the total value is equal to or less than the threshold value can be considered.

(5) Neighborhood pattern calculation step 450
In the neighborhood pattern calculation step 450, for S _j obtained by the calculation of the change in the amount of components, the value rated with the maximum value of 1 is obtained and used as R _j . Further, the m / z value corresponding to the value of j corresponding to the maximum value is the current m / z value, and the deviation from the m / z value of the target component can be obtained. Further, R _j can be used in the ionic strength correction step 460, and the deviation of the m / z value is used in the m / z value correction step 470.

Here, the value of S _j is cleared.

(6) Ionic strength correction step 460
The ionic strength correction step 460 is performed in the same manner as in Example 2.

(7) m / z value correction step 470
The m / z value correction step 470 is performed in the same manner as in the second embodiment.

(8) End determination step 480
The end determination step 480 is performed in the same manner as in the second embodiment.

In Example 3, the same effect as in Example 1 can be obtained.

The above-mentioned Examples 1, 2 and 3 relate to the detection of ions derived from the target component, respectively. If the amount of the target component is small, the present invention may be applied to other components having the same deviation of the m / z value as the target component, and the m / z value of the target component may also be corrected. Will be.

For example, carbon 13 (composed of 6 protons and 7 neutrons), which is a stable isotope, is used as an internal standard to replace some of the carbons that make up the target component, and it is measured at the same time as the target component in quantitative measurement. do. At that time, the ions derived from the target component are measured by SIM or SRM as before, and the present invention is applied to the ions of the internal standard substance to correct the ionic strength and the m / z value. At that time, the deviation of the m / z value of the ion derived from the target component is regarded as the same as that of the internal standard substance, and the ionic strength correction and the m / z value correction corresponding to the deviation of the m / z value of the ion corresponding to the target component are considered. To apply.

The above-mentioned example is an example in which an internal standard substance is used, but it is not always necessary to use an internal standard substance. That is, without using the internal standard substance, the ionic strength detection unit 520 searches for the vicinity of the ion showing the same deviation as the m / z value of the target component, and the neighborhood pattern calculation unit searches for the vicinity of the ionic strength of the searched ion. A pattern can be obtained, and based on the result, the ionic strength of the target component can be corrected by the ionic strength correction unit 550, and the m / z value can be corrected by the m / z value correction unit 560.

According to Examples 1 to 3 of the present invention described above, the following effects can be obtained in quantitative measurement by SIM or SRM.

(1) Compensation for the ionic strength reduced due to the deviation of the m / z value In the original quantitative measurement, it is ideal to obtain the time course of the ionic strength of the m / z value corresponding to the peak top of the target component. According to the present invention, even if the m / z value of the device is deviated due to the influence of temperature, humidity, etc., the deviated situation can be detected from the pattern of the search points near the m / z value being measured. Further, the measured ionic strength can be converted into the ionic strength that should be able to be measured originally. It is important to prevent the fluctuation of the ionic strength per unit amount of the sample component due to the deviation of the m / z value in maintaining the quantifiable concentration range and accuracy.

(2) Acquisition of voucher that does not deviate from m / z value In quantitative measurement by SIM or SRM, a voucher that does not deviate from m / z value can be directly obtained together with the quantitative value.

(3) Automatic correction of m / z value deviation The m / z value deviation can be detected from the neighborhood pattern of the target component. That is, it is possible to correct the deviation of the m / z value in real time. Even when the m / z value of the device gradually deviates, it is possible to maintain more optimum quantitative performance.

As a side effect, for example, since the process of inserting a scan measurement during quantitative measurement becomes unnecessary, it becomes possible to devote more time to the device to detect ions derived from the target component, and the sensitivity of quantitative measurement. It also contributes to improvement.

In the above-mentioned example, the deviation of the m / z value is automatically corrected, but the present invention is established even if the deviation of the m / z value is omitted.

That is, according to the present invention, the deviation of the m / z value due to the change of the control condition is detected, the sensitivity required for the quantitative analysis is maintained, and the voucher for the deviation of the m / z value is given, and the deviation of the m / z value is given. It is possible to realize a mass spectrometer and a mass spectrometry method that can compensate for the amount of ions reduced due to the displacement.

110: Sample supply device, 120: Mass analyzer, 121: Ionization section, 122: Mass analyzer, 123: Detection section, 124: Control section, 130: Input / output device, 210: Peak before calibration, 220: After calibration Peak, 230: Half price width, 310: Calibration curve, 410: Initial setting step, 420: Neighborhood search step, 430: Component amount change calculation step, 440: Neighborhood pattern determination determination step, 450: Neighborhood pattern calculation step, 460 : Ion intensity correction step, 470: m / z value correction step, 480: End determination step, 510: Mass filter control unit, 520: Ion intensity detection unit, 530: Component amount change calculation unit, 540: Neighborhood pattern calculation unit 550: Ion intensity correction unit, 560: m / z value correction unit, 610: Mass spectrum at the time of calibration, 620: M / z value M-Δ search point (search point 1), 630: m / z value M Search point (peak top) (search point 2), 640: search point with m / z value M + Δ (search point 3), 650: example of mass spectrum when the amount of components increases, 660: measured value at search point 1. , 670: measured value of search point 2 (measured value of peak top), 680: measured value of search point 3, line segment connecting search points in 690: 1 cycle, 710: change of search point 1, 720: Change of search point 2, 730: Change of search point 3, 810: Mass spectrum immediately after calibration, 820: 0.05 deviation to the high m / z value side, 830: 0.10 to the high m / z value side Displaced state, 840: measured value at search point 1, 850: measured value at search point 2, 910: m / z Error (deviation of m / z value), 920: I (ion intensity), 930: R (ion). Intensity ratio), 940: R'(expected measurement ratio of ion intensity), 950: Score (score), 1010: Line line showing the relationship between Score and m / z value deviation 1110: Target (definition region of target component) ), 1111: Top (m / z value of pea top), 1112: Wide (half price width of peak), 1113: Dwell Time (uptake time), 1120: Search (definition area of neighborhood search condition), 1121: Point Number. (Score of search points), 1122: Delta (interval of search points), 1123: Threat (threshold value for determination of neighborhood pattern determination), 1130: Direction (definition area of m / z value correction condition), 1131: Step. (Correction step) 1132: Maximum (maximum correction value), 1210: Log Title, 1220: m / z value of target component, 1230: log item, 1240: log substance, 1310: mass spectrum when component amount is constant, 1320: search point of m / z value M-Δ / 2. (Search point 1), 1330: Search point with m / z value M + Δ / 2 (search point max), 1340: Mass spectrum measured when the component amount is constant, 1350: Mass spectrum when the component amount increases, 1360: Measured value of search point 1, 1370: Measured value of search point max, 1380: Mass spectrum measured when the amount of components increases, 1410: Change of search point 1, 1420: Change of search point max, 1430: Change of search point corresponding to peak top, 1510: Mass spectrum immediately after calibration, 1520: 0.05 deviation to high m / z value side, 1530: 0.10 deviation to high m / z value side, 1540: measured value of search point 1, 1550: measured value of search point 2, 1560: peak top, 1610: tangent line 1, 1620: tangent line 2, 1630: intersection of tangent line 1 and tangent line 2.

Claims (15)

An ionization unit that ionizes sample components, a mass spectrometry unit that selects ions supplied by the ionization unit, a detection unit that measures the intensity of ions selected by the mass spectrometry unit, an ionization unit, and the mass spectrometry. In a mass spectrometer including a unit and a control unit that controls the operation of the detection unit.
The control unit
A mass spectrometric control unit that switches the control conditions of the mass spectrometric unit in order to select multiple m / z values in the vicinity of the m / z value derived from the target component.
An ion intensity detecting unit that detects the ion intensity of the m / z value selected by the mass spectrometry control unit, and an ion intensity detecting unit.
A change calculation unit for the amount of components that calculates the change in ionic strength detected by the ion intensity detection unit, and a change calculation unit.
A neighborhood pattern calculation unit that calculates the ratio of the ionic strength of the m / z values at the plurality of locations in a state where the amount of components is constant and calculates the neighborhood pattern.
An ionic strength correction unit that compensates for the lack of ionic strength measured based on the neighborhood pattern, and
A mass spectrometer that measures the change over time in the ionic strength of the m / z value derived from the target component. In the mass spectrometer according to claim 1,
The control unit is a mass spectrometer including an m / z value correction unit that corrects the control conditions of the mass spectrometry control unit based on the neighborhood pattern. In the mass spectrometer according to claim 1,
Of the m / z values in the vicinity of the m / z value derived from the target component, the m / z values at both ends of the m / z value derived from the target component are located at positions lowered by several percent from the peak top. A mass spectrometer characterized by having a maximum of more than half of the peak. In the mass spectrometer according to claim 1,
Since the mass spectrometric control unit selects m / z values at a plurality of locations near the m / z value derived from the target component, the m / z value derived from the target component is −0.5 to +0.5. A mass spectrometer characterized by being capable of scan measurement within the range of. In the mass spectrometer according to claim 1,
The component amount change calculation unit is a mass spectrometer characterized in that the change in ionic strength is calculated by a plurality of cycles and the change in the component amount is calculated from the previous and next cycles by an interpolation method. In the mass spectrometer according to claim 5,
The neighborhood pattern calculation unit is a mass spectrometer characterized in that the ionic strength per unit component amount is set as a neighborhood pattern from the change in the component amount calculated by the interpolation method. In the mass spectrometer according to claim 2,
The neighborhood pattern calculation unit determines the score by referring to the relationship between the registered neighborhood pattern, the score, and the deviation of the m / z value, and the ion intensity correction unit determines the ion intensity from the ion intensity ratio corresponding to the score. The m / z value correction unit corrects the mass spectrometer, and corrects the deviation of the m / z value corresponding to the score. In the mass spectrometer according to claim 4,
The component amount change calculation unit is a mass spectrometer characterized in that the change in the component amount is obtained by a tangent line tangent to the mass spectrum obtained by the scan measurement. In the mass spectrometer according to claim 4,
The component amount change calculation unit is a mass spectrometer characterized in that the change in the component amount is obtained by a quadratic function circumscribing the mass spectrum obtained by the scan measurement. In the mass spectrometer according to claim 2,
The ion intensity detection unit searches for the vicinity of ions showing the same deviation as the m / z value derived from the target component, and the neighborhood pattern calculation unit calculates the vicinity pattern of the ion intensity of the searched ions. A mass spectrometer characterized in that the ion intensity of a target component is corrected by the ion intensity correction unit and the m / z value is corrected by the m / z value correction unit. In a mass spectrometry method in which a sample component is ionized, ionized ions are selected, and the intensity of the selected ions is measured.
A neighborhood search step that continuously detects the ionic strength of m / z values at multiple locations near the m / z values derived from the target component, and
The change calculation step of the component amount to calculate the change of the detected ionic strength, and
A neighborhood pattern calculation step for obtaining the ratio of the ionic strength of the m / z value at a plurality of locations near the m / z value derived from the target component in a state where the component amount is constant, and
An ionic strength correction step that compensates for the lack of ionic strength measured based on the neighborhood pattern, and
A mass spectrometric method comprising the above, and measuring the change with time of the ionic strength of the m / z value derived from the target component. In the mass spectrometry method according to claim 11,
A mass spectrometric method further comprising an m / z value correction step for correcting a detected m / z value based on a deviation of m / z values at a plurality of nearby locations. In the mass spectrometry method according to claim 11,
Of the m / z values in the vicinity of the m / z value derived from the target component, the m / z values at both ends of the m / z value derived from the target component are located at positions lowered by several percent from the peak top. A mass spectrometric method characterized by having a maximum of more than half of the peak. In the mass spectrometry method according to claim 11,
Since the m / z values in the vicinity of the m / z value derived from the target component are selected, the m / z value derived from the target component can be scanned and measured in the range of -0.5 to +0.5. A mass spectrometric method characterized by being. In the mass spectrometry method according to claim 11,
A mass spectrometric method characterized in that changes in ionic strength are calculated by a plurality of cycles, and changes in the amount of components are calculated by a quadratic equation from the cycles before and after.

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