Detection method of triple quadrupole mass spectrometer

Abstract

The invention belongs to a mass spectrometry technology, and particularly provides a detection method of a triple quadrupole mass spectrometer, which comprises the following steps: A1, setting basic parameters of the mass spectrometer, and establishing compound acquisition initial parameters; the basic parameters comprise detection window time T11 and target detection time T12, and the initial parameters comprise names of compounds, parent ions and channel ion pairs; a2, method parameters are optimized according to the basic parameters and the initial parameters, and the method parameters comprise method time T21, the fragment number M and fragment scanning time T22; and A3, performing ionization, ion screening, collision and detection by the mass spectrometer according to the parameters of the method. The method has the advantages of good accuracy, high throughput and the like.

Description

Technical Field

[0001] This invention relates to mass spectrometry, and particularly to a detection method using a triple quadrupole mass spectrometer. Background Technology

[0002] A triple quadrupole mass spectrometer is a high-precision analytical instrument based on quadrupole mass analysis technology, characterized by high resolution and high sensitivity. By connecting three quadrupoles in series and simultaneously controlling different operating modes of each quadrupole, ions with suitable mass-to-charge ratios can pass through, while other ions are destroyed by collision, thus enabling qualitative and quantitative detection of compounds.

[0003] One operating mode of a triple quadrupole mass spectrometer is multiple reaction monitoring (MRM), which detects reactions by selecting precursor and daughter ion pairs. It offers high selectivity and can simultaneously monitor multiple ion pairs, enabling the detection of multiple compounds. This mode can achieve a speed of up to 500 channels / second. However, this method has the following drawbacks: 1. Lowest detection limit. To increase throughput, the scan time has been shortened. For example, with 500 channels / second, the actual scan time is 1 millisecond, which is far lower than the minimum detection limit requirement of 10 milliseconds (determined by the capability of the triple quadrupole mass spectrometer).

[0004] 2. Low throughput. If the scan time is adjusted to 10 milliseconds, then the actual number of channels per second = 1 × 1000 / (10 + 1) = 90. In the detection of complex matrix samples, the number of substances to be detected often exceeds 200, and each substance must monitor more than 2 ion pairs. Sometimes an internal standard is also required. The actual requirement is more than 500 channels / second, which is far from meeting the requirements of complex matrix sample detection. Summary of the Invention

[0005] To address the shortcomings of the existing technical solutions, this invention provides a detection method using a triple quadrupole mass spectrometer.

[0006] The objective of this invention is achieved through the following technical solution: The detection method of triple quadrupole mass spectrometer includes the following steps: A1. Set the basic parameters of the mass spectrometer and establish the initial parameters for compound acquisition; the basic parameters include the detection window time T. 11 And target detection time T 12 The initial parameters include the name of the compound, the parent ion, and the channel ion pair; A2. Based on the aforementioned basic parameters and initial parameters, optimize the method parameters, including the method time T. 21 Number of segments M and segment scan time T 22 ; A3. The mass spectrometer performs ionization, ion screening, collision, and detection according to the parameters of the method described above.

[0007] Compared with the prior art, the present invention has the following beneficial effects.

[0008] 1. This application utilizes the retention time characteristic to control the corresponding channels to be scanned only at appropriate times, which greatly improves throughput.

[0009] Taking the most extreme case as an example, assuming the method time is 30 minutes, the detection window time is 10 seconds, the target detection time is 1 second, the clear time is 1 millisecond, and the minimum scan time is 10 milliseconds, with the instrument throughput remaining unchanged at 90 per second, the actual instrument throughput is increased by approximately 30·60 / 10=180 times.

[0010] 2. Dynamically adjust the scanning time to ensure high throughput while maintaining an effective signal-to-noise ratio.

[0011] The scanning time is dynamically adjusted based on the number of channels in the current time segment. For example, if the current number of channels is 40, the scanning time is 1·1000 / 40=25 milliseconds, which effectively improves the signal-to-noise ratio and greatly enhances the accuracy of the instrument.

[0012] 3. Sort and scan data in a reasonable manner to ensure data validity.

[0013] All channels are scanned at the most appropriate time, which greatly improves throughput and data validity. Attached Figure Description

[0014] The disclosure of this invention will become more readily understood with reference to the accompanying drawings. It will be readily understood by those skilled in the art that these drawings are merely illustrative of the technical solutions of this invention and are not intended to limit the scope of protection of this invention. In the drawings: Figure 1 This is a schematic flowchart of the detection method in Embodiment 1 of the present invention. Detailed Implementation

[0015] Figure 1 The following description illustrates optional embodiments of the invention to teach those skilled in the art how to implement and reproduce the invention. Some conventional aspects have been simplified or omitted to teach the technical solutions of the invention. Those skilled in the art should understand that variations or substitutions derived from these embodiments will be within the scope of the invention. Those skilled in the art should understand that the following features can be combined in various ways to form multiple variations of the invention. Therefore, the invention is not limited to the optional embodiments described below, but is defined only by the claims and their equivalents.

[0016] Example 1

[0017] The detection method of the triple quadrupole mass spectrometer in this embodiment, such as... Figure 1 As shown, the steps include: A1. Set the basic parameters of the mass spectrometer, such as: Detection window time T 11 The width of the detection window for each compound ranges from 10 to 60 seconds, with 20 seconds generally recommended.

[0018] Target detection time T 12 The total time for scanning all channels in the segment once, ranging from 1 second to 10 seconds.

[0019] Ion clearance time T 13 The time for clearing between each channel scan is determined by the capability of the triple quadrupole mass spectrometer; the shorter the time, the greater the capability.

[0020] Minimum scan time T 14 The minimum scan time for each channel is used to meet the signal-to-noise ratio requirements. This time is determined by the capability of the triple quadrupole mass spectrometer; the shorter the time, the stronger the capability, such as T. 14 =10ms.

[0021] Maximum scan time T 15 The maximum scan time for each channel, used to control the scan speed, such as T. 15 =250ms.

[0022] Establish initial parameters for compound acquisition, such as: Establish the name of the compound being detected, the parent ion, the daughter ion, and the RT time T. 17 Set the initial parameters and save them.

[0023] Channel ion pairs: At least two ion pairs are required for each compound.

[0024] Retention time: The retention time T of a compound 17 This time is the time it takes for a compound to pass through a separation module (such as a chromatographic column), and this time is relatively fixed.

[0025] A2. Based on the aforementioned basic and initial parameters, optimize the method parameters, specifically as follows: Method time T 21 =(T 17 ) max +T 11 / 2; Fragment time T 22 =T 12 ×10.

[0026] Number of fragments M = [(T 17 ) max +T 21 / 2] / (T12 ×10). If M>360, recalculate T. 22 And M, first set M=360, T 22 =T 21 / M.

[0027] Obtain the start and end times of each segment. The segment start time = the end time of the previous segment, and the segment end time = start time + segment time.

[0028] Calculate the channel time range, channel start time = T 17 -T 12 / 2, Channel end scan time = T 17 +T 12 / 2.

[0029] Divide each segment into channels, loop through each segment, then loop through each channel, comparing the start and end times of the segment with the start and end times of the channel. If the end time of the segment is greater than the start time of the channel, and the end time of the segment is less than or equal to the end time of the channel, the channel is included in the loop.

[0030] Fragment scan time T 22 =T 12 ×1000 / N, where N is the number of channels contained in the segment.

[0031] If N=0, then T 22 =T 15 .

[0032] If T 22 <T 14 Then T 22 =T 14 .

[0033] If T 22 >T 15 Then T 22 =T 15 .

[0034] If T 22 If the time is not an integer, adjust the start and end times of the segment: End time of the current segment = T 22 Round down by N, and the start time of the next segment equals the end time of the previous segment (part of the time is included in the next segment, and so on to complete the scan time calculation for all segments).

[0035] Optimize the method time. Based on the calculation results above, the method is divided into several segments, and the channel scan time in each segment equals the segment scan time. To ensure effective detection of channels in the last segment, the time for one channel needs to be extended (i.e., the 360th segment needs to be scanned twice), T 22 =End time of the last segment +Segment time of the last segment.

[0036] A3. The mass spectrometer performs ionization, ion screening, collision, and detection according to the parameters of the method described above.

[0037] Example 2

[0038] This is an application example of the detection method in Example 1 of this embodiment.

[0039] like Figure 1 As shown, the detection method includes the following steps: A1. The processor accepts parameter settings, including: T 11 =10s, T 12 =1s.

[0040] T 13 =0s,T 14 =10ms, T 15 =250ms, both determined by the capabilities of the mass spectrometer.

[0041] Channel ion pairs: 36,000.

[0042] Retention time: 36,000 items, starting from 5, increasing by 10 seconds for every 100 items. For example: [5, 5, 5, 5, ……], a total of 100.

[0043] [15,15,15,15,……], a total of 100.

[0044] [25,25,25,25,……], a total of 100.

[0045] ... [3595, 3595, 3595, 3595, ...], a total of 100.

[0046] A2. Processor optimization methods; T 21 =3595 + 10 / 2 = 3600(s), T 22 =1*10=10(s).

[0047] M = 3600 / 10 = 360.

[0048] Segment start time = [0, 10, 20, ..., 3600].

[0049] Segment end time = [10, 20, 30, ..., 3600].

[0050] Channel start time = [0,0,0,……,10,10,10,…,3590].

[0051] Channel end time = [10,10,10,……,20,20,20,…,3600].

[0052] N=[100,100,100,……,100].

[0053] T 22 =[10,10,10,……,10].

[0054] The number of loops in the segment = T 22 / N*scan time, found that the number of cycles for each channel = 10×1000 / (100×10) = 10 times, which is exactly divisible, so no dynamic adjustment is needed at this time.

[0055] Optimize the workflow. Divide the workflow into 360 segments. The first segment includes 100 channels from 0 to 99, and this segment is scanned from 0s to 10s, with a total scan time of 10ms for all channels. The second segment includes 100 channels from 100 to 199, and this segment is scanned from 10s to 20s, with a total scan time of 10ms for all channels. This continues until the last segment, which requires two scans. Therefore, the workflow is divided into 361 segments, and the workflow time is 3610s.

[0056] The optimized working method parameters are sent to the mass spectrometer.

[0057] S3: After receiving the method, the mass spectrometer performs detection and simultaneously starts the separation module and ion source.

[0058] The separation module separates the compounds from the sample at the retention time point.

[0059] The ion source receives and ionizes various compounds from the separation module.

[0060] Example 3

[0061] This is an application example of the detection method in Example 1 of this embodiment.

[0062] like Figure 1 As shown, the detection method includes the following steps: A1. The processor accepts parameter settings, including: T 11 =20s, T 12 =1s.

[0063] T 13 =0s,T 14 =10ms, T 15 =250ms, both determined by the capabilities of the mass spectrometer.

[0064] Channel ion pairs: 36,000.

[0065] Retention period: 36,000, starting from 5, increasing by 10 for every 100, e.g.: [5, 5, 5, 5, ……], a total of 100.

[0066] [15,15,15,15,……], a total of 100.

[0067] [25,25,25,25,……], a total of 100.

[0068] ... [3595, 3595, 3595, 3595, ...], a total of 100.

[0069] A2. Processor optimization methods; T 21 =3595 + 20 / 2 = 3605s, T 22 =1*10=10s.

[0070] M = 3605 / 10 = 360.5; Since M > 360, the segment time and number of segments need to be recalculated, i.e., T. 23 =3605 / 360=10.01s.

[0071] Segment start time = [0, 10.01, 20.02, ..., 3594.99].

[0072] Segment end time = [10.01, 20.02, 30.03, ..., 3605].

[0073] Channel start time = [0,0,0,……,15,15,15,…,3595,3595,3595,……,3695].

[0074] Channel end time = [15,15,15,……,25,25,25,……,3605,3605,3605,……,3605].

[0075] M=[200,200,200,……,200].

[0076] T 22 =[10,10,10,……,10].

[0077] The number of loops in the segment = T 22 / N*scan time, the cycle count for channels 1 to 99 is 10.01×1000 / (200×10)=5.005, which is not divisible. Therefore, dynamic adjustment is needed: For the first segment, the number of loops is 10.01 × 1000 / (200 × 10) = 5.005. Rounding down 5 times, the segment time is 5 × 200 × 10 / 1000 = 10 seconds. Any excess 0.01 seconds is carried over to the next segment.

[0078] For the second segment, the number of loops is 10.02 × 1000 / (200 × 10) = 5.01. Rounding down 5 times, the segment time is 5 × 200 × 10 / 1000 = 10 seconds. The extra 0.02 seconds is carried over to the next segment.

[0079] The third segment has a loop count of 10.03 × 1000 / (200 × 10) = 5.015. Rounding down 5 times, the segment duration is 5 × 200 × 10 / 1000 = 10 seconds. Any excess 0.03 seconds is carried over to the next segment.

[0080] And so on.

[0081] For the 100th segment, the number of loops is 11 × 1000 / (200 × 10) = 5.5. After rounding down 5 times, the segment time is 5 × 200 × 10 / 1000 = 10 seconds. The extra 1 second is discarded.

[0082] After dynamic adjustment: Segment start time = [0, 10, 20, ..., 3584, 3594].

[0083] Segment end time = [10, 20, 30, ... 3594, 3604].

[0084] Optimized working method: The method is divided into 360 segments. The first segment includes channels 0 to 199 (200 channels), and scanning is performed from 0s to 10s, with a scan time of 10ms for all channels in this segment. The second segment includes channels 100 to 299 (200 channels), and scanning is performed from 10s to 20s, with a scan time of 10ms for all channels in this segment. This continues until the last segment, which requires two scans. Therefore, the method is divided into 361 segments, with a total method time of 3614s. The optimized working method is then sent to the mass spectrometer.

[0085] The optimized working method parameters are sent to the mass spectrometer.

[0086] S3: After receiving the method, the mass spectrometer performs detection and simultaneously starts the separation module and ion source.

[0087] The separation module separates the compounds from the sample at the retention time point.

[0088] The ion source receives and ionizes various compounds from the separation module.

Claims

1. A detection method using a triple quadrupole mass spectrometer, characterized in that, The detection method includes the following steps: A1. Set the basic parameters of the mass spectrometer and establish the initial parameters for compound acquisition; the basic parameters include the detection window time T. 11 And target detection time T 12 The initial parameters include the name of the compound, the parent ion, and the channel ion pair; A2. Based on the aforementioned basic parameters and initial parameters, optimize the method parameters, including the method time T. 21 Number of segments M and segment scan time T 22 ; A3. The mass spectrometer performs ionization, ion screening, collision, and detection according to the parameters of the method described above.

2. The detection method according to claim 1, characterized in that, The basic parameters also include ion clearance time T. 13 Minimum scan time T 14 and maximum scan time T 15 ; The initial parameters also include retention time T. 17 .

3. The detection method according to claim 2, characterized in that, The parameters of the method are: T 21 =(T 17 ) max +T 11 / 2; Fragment time T 22 =T 12 ×10;M=[(T 17 ) max +T 11 / 2] / (T 12 ×10); Obtain the start and end times of each segment. The start time of a segment = the end time of the previous segment, and the end time of a segment = start time + segment time. Calculate the channel time range, channel start time = T 17 -T 12 / 2, Channel end scan time = T 17 +T 12 / 2; Divide each segment into channels, loop through each segment, then loop through each channel again, and compare the start and end times of the segment with the start and end times of the channel. If the end time of the segment is greater than the start time of the channel and the end time of the segment is less than or equal to the end time of the channel, then the segment contains the channel. T 22 =T 12 ×1000 / N, where N is the number of channels contained in the segment; If N=0, then T 22 =T 15 ; If T 22 <T 14 Then T 22 =T 14 ; If T 22 >T 15 Then T 22 =T 15。 4. The detection method according to claim 3, characterized in that, If M > 360, recalculate T. 23 And M, first set M=360, T 22 =T 21 / M.

5. The detection method according to claim 3, characterized in that, If T 22 If the time is not an integer, adjust the start and end times of the segment: End time of the current segment = T 22 Round down by N, and the start time of the next segment equals the end time of the previous segment.

6. The detection method according to claim 5, characterized in that, T 22 =End time of the last segment +Segment time of the last segment.

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