Chromatogram processing method, device, equipment and medium

Abstract

The invention discloses a chromatogram processing method, device and equipment and a medium. The method comprises the following steps: acquiring a standard sample chromatogram and a to-be-detected sample chromatogram; judging whether the chromatogram of the sample to be detected can be quantitatively analyzed or not by utilizing the chromatogram of the standard sample; and correcting the chromatogram of the to-be-detected sample by using the chromatogram of the standard sample in response to the situation that quantitative analysis cannot be performed on the chromatogram of the to-be-detected sample. Therefore, based on a known standard sample chromatogram, whether the chromatogram possibly containing matrix interference can be applied to quantitative calculation or not is evaluated, interference information of a matrix on a chromatographic peak is corrected and eliminated, and the precision in the quantitative process is improved.

Description

Technical Field

[0001] The present application relates to the field of mass spectrometry technology, and in particular to a chromatogram processing method, device, equipment and medium. Background Art

[0002] Liquid chromatography-mass spectrometry is usually used for qualitative and quantitative analysis of organic samples. Its analysis process covers the steps of separation, ionization, mass spectrometry scanning, spectrum integration and quantitative calculation of mixed samples. Among them, quantitative calculation is the last key link, which involves using the existing standard curve equation to calculate the concentration of unknown samples to be tested. However, when the chromatogram of the unknown concentration sample being calculated is in extremely poor condition, the calculation result may have a large deviation, resulting in distortion of the calculation result.

[0003] In order to avoid distortion of the calculation results, it is necessary to evaluate the spectra involved in the calculation to determine whether they are suitable for quantitative calculation. The commonly used method is relatively cumbersome: by replacing the injection method and re-injecting, the influence of the matrix on the peak shape can be reduced. When performing quantitative calculations, the spectrum data may be partially biased due to the interference of the matrix. At this time, various means are used for correction, such as smoothing or manual selection of the integration peak area. Such operations usually require manual processing. When the sample size is small, manual processing is acceptable, but once the sample size increases, manual processing will become time-consuming and laborious.

[0004] Therefore, how to provide a reliable and stable automated processing method to cope with the deviation effect caused by the matrix is ​​a technical problem that technical personnel in this field urgently need to solve. Summary of the invention

[0005] Based on the above problems, the present application provides a chromatogram processing method, device, equipment and medium.

[0006] In some embodiments, the method comprises:

[0007] Obtaining a chromatogram of a standard sample and a chromatogram of a sample to be tested;

[0008] Using the standard sample chromatogram, determining whether the sample chromatogram to be tested can be quantitatively analyzed;

[0009] In response to the chromatogram of the sample to be tested being unable to be quantitatively analyzed, the chromatogram of the sample to be tested is corrected using the chromatogram of the standard sample.

[0010] As a possible implementation, the method further includes:

[0011] In response to the chromatogram of the sample to be tested meeting the basic requirements of the quantitative analysis, the chromatogram of the standard sample is used to suppress matrix interference on the chromatogram of the sample to be tested.

[0012] As a possible implementation manner, the use of the standard sample chromatogram to determine whether the chromatogram of the sample to be tested can be quantitatively analyzed includes:

[0013] Obtaining the overflow area, wherein the overflow area is the peak area of ​​the portion where the waveform of the chromatogram of the sample to be tested is higher than the waveform of the chromatogram of the standard sample;

[0014] Obtaining a standard sample peak area, wherein the standard sample peak area is a peak area of ​​a chromatogram waveform of the standard sample;

[0015] It is determined whether the area of ​​the overflow portion does not exceed a preset proportion of the peak area of ​​the standard sample.

[0016] As a possible implementation manner, in response to the chromatogram of the sample to be tested being unable to perform quantitative analysis, the chromatogram of the sample to be tested is corrected using the chromatogram of the standard sample, including:

[0017] In response to the overflow portion area exceeding a preset ratio of the standard sample peak area, the chromatogram of the sample to be tested is corrected using the standard sample chromatogram.

[0018] As a possible implementation manner, the use of the standard sample chromatogram to calibrate the sample chromatogram to be tested includes:

[0019] The portion of the chromatogram waveform of the sample to be tested that is higher than the waveform of the chromatogram waveform of the standard sample is corrected to the waveform of the chromatogram waveform of the standard sample at the corresponding portion.

[0020] As a possible implementation manner, the use of the standard sample chromatogram to suppress matrix interference in the chromatogram of the sample to be tested includes:

[0021] The portion of the chromatogram waveform of the sample to be tested that is higher than the waveform of the chromatogram waveform of the standard sample is corrected to the waveform of the chromatogram waveform of the standard sample at the corresponding portion.

[0022] In some embodiments, the apparatus comprises:

[0023] An acquisition module, used for acquiring a chromatogram of a standard sample and a chromatogram of a sample to be tested;

[0024] A judgment module, used to judge whether the chromatogram of the sample to be tested can be quantitatively analyzed by using the chromatogram of the standard sample;

[0025] The correction module is used for correcting the chromatogram of the sample to be tested by using the chromatogram of the standard sample in response to the chromatogram of the sample to be tested being unable to be quantitatively analyzed.

[0026] As a possible implementation manner, the device further includes:

[0027] The interference suppression module is used to suppress matrix interference of the chromatogram of the sample to be tested by using the chromatogram of the standard sample in response to the chromatogram of the sample to be tested meeting the basic requirements of the quantitative analysis.

[0028] In some embodiments, the chromatogram processing device comprises: a memory and a processor;

[0029] The memory is used to store program code and transmit the program code to the processor;

[0030] The processor is used to execute the steps of the chromatogram processing method according to the program code.

[0031] In some embodiments, the computer-readable storage medium stores a computer program, and when the computer program runs on a chromatogram processing device, the chromatogram processing device performs the steps of chromatogram processing.

[0032] Compared with the prior art, this application has the following beneficial effects:

[0033] This application can evaluate whether a chromatogram that may contain matrix interference can be used for quantitative calculation based on a known standard sample chromatogram, correct and eliminate the interference information of the matrix on the chromatographic peak, and improve the accuracy of the quantitative process. BRIEF DESCRIPTION OF THE DRAWINGS

[0034] In order to more clearly illustrate the embodiments of the present application or the technical solutions in the prior art, the drawings required for use in the embodiments or the description of the prior art will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present application. For ordinary technicians in this field, other drawings can be obtained based on these drawings without paying creative work.

[0035] Figure 1 A chromatogram of a sample to be tested provided in an embodiment of the present application;

[0036] Figure 2 A flow chart of a chromatogram processing method according to an embodiment of the present application;

[0037] Figure 3 A chromatogram of a standard sample provided in an embodiment of the present application;

[0038] Figure 4 A chromatogram of a standard sample of another embodiment provided in the embodiment of the present application;

[0039] Figure 5A chromatogram calibration diagram of a sample to be tested provided in an embodiment of the present application;

[0040] Figure 6 A comparison chart of the chromatogram of a sample to be tested before and after calibration in an embodiment provided in the present application;

[0041] Figure 7 A structural diagram of a chromatogram processing device according to an embodiment of the present application;

[0042] Figure 8 A structural diagram of a chromatogram processing device according to an embodiment of the present application. DETAILED DESCRIPTION

[0043] The chromatogram processing method, device, equipment and medium provided in the present application can be used in the field of mass spectrometry. The above is only an example and does not limit the application field of the chromatogram processing method, device, equipment and medium provided in the present application.

[0044] High performance liquid chromatography-tandem mass spectrometry (LC-MS / MS) has been widely used in many detection fields due to its high sensitivity, strong specificity and rapid analysis capabilities. However, for samples with complex matrices, the matrix effect in the detection process becomes a key factor affecting the accuracy and precision of the analysis results. Therefore, analysts should pay great attention to the matrix effect problem.

[0045] In LC-MS / MS analysis, non-target analytes, as co-elutants in the sample, will affect and interfere with the ionization process of the target analyte. These effects and interferences are collectively referred to as matrix effects. The matrix effect occurs because non-target analytes compete with the target substance for charge when passing through the spray needle together, causing them to adsorb the droplets produced tightly together, preventing the droplets from splitting into smaller droplets, thereby changing the surface tension of the charged droplets. This change will cause the ionization efficiency of the target substance to decrease or increase, causing the response signal to decrease or increase, thereby producing a matrix suppression effect or a matrix enhancement effect. See Figure 1 , the matrix peak shape will affect the peak search results of the experimental data, and then affect the calculation of the chromatogram of the analyte and its quantitative results.

[0046] The present application is particularly suitable for data processing of high performance liquid chromatography triple quadrupole mass spectrometer (LC-MS for short). LC-MS is usually used for qualitative and quantitative analysis of organic samples, and its analysis process includes steps such as separation, ionization, mass spectrometry scanning, spectrum integration and quantitative calculation of mixed samples; among them, quantitative calculation is the last key link. The accuracy of quantitative calculation depends on the accuracy of peak shape calculation. If the influence of matrix (components other than analyte in sample) on chromatographic peak cannot be effectively excluded during quantitative analysis, it will directly affect the accuracy of analysis results.

[0047] The terms "first", "second", "third" and "fourth" etc. in the specification, claims and drawings of this application are used to distinguish different objects rather than to limit a specific order.

[0048] In the embodiments of the present application, the words "as an example" or "for example" are used to indicate examples, illustrations or explanations. Any embodiment or design described as "as an example" or "for example" in the embodiments of the present application should not be interpreted as being more preferred or more advantageous than other embodiments or designs. Specifically, the use of the words "as an example" or "for example" is intended to present the relevant concepts in a specific way.

[0049] The terms used in the implementation section of this application are only used to explain the specific embodiments of this application and are not intended to limit this application.

[0050] In order to enable those skilled in the art to better understand the solution of the present application, the technical solution in the embodiments of the present application will be clearly and completely described below in conjunction with the drawings in the embodiments of the present application. Obviously, the described embodiments are only part of the embodiments of the present application, not all of the embodiments. Based on the embodiments in the present application, all other embodiments obtained by ordinary technicians in this field without creative work are within the scope of protection of this application.

[0051] Method Embodiment

[0052] See also Figure 2 , which is a chromatogram processing flow chart provided in an embodiment of the present application, the process 200 includes:

[0053] Step 201, obtaining a chromatogram of a standard sample and a chromatogram of a sample to be tested.

[0054] The chromatogram of the sample to be tested can be Figure 1 The peak shape diagram with matrix interference is shown, for example, a chromatogram of a patient's blood sample. In the figure, the matrix peak shape has an impact on the peak finding results of the experimental data.

[0055] The standard sample chromatogram is purer than the sample to be tested, and its chromatogram is smoother and has obvious peak characteristics. Figure 3 , Figure 4 , two possible standard sample chromatograms are shown.

[0056] Step 202: using the standard sample chromatogram, determine whether the sample chromatogram to be tested can be quantitatively analyzed.

[0057] Quantitative calculation is the process of calculating the concentration of unknown samples using the existing standard curve equation. When the chromatogram of the unknown concentration sample is in a very poor state, the calculated result will be very poor, which will lead to distortion of the calculated result. Therefore, before conducting quantitative analysis, it is necessary to determine whether the chromatogram of the sample to be tested can be quantitatively analyzed.

[0058] When the peak shape of the chromatogram of the sample to be tested and the peak shape of the chromatogram of the standard sample meet a certain relationship, it can be determined that the peak shape of the chromatogram of the sample to be tested meets the integration requirements and quantitative analysis can be performed. The specific relationship that needs to be met is not limited here.

[0059] For example, the peak shape can be limited by the fluctuation range of the peak shape to determine whether it meets the integration requirements, and the peak shape of the chromatogram of the test sample and the peak shape of the chromatogram of the standard sample can be compared. When the ratio of the peak area of ​​the chromatogram of the test sample to the peak area of ​​the chromatogram of the standard sample meets the preset relationship, it can be determined that the peak shape of the test sample meets the requirements and can be used for quantitative analysis.

[0060] As a possible implementation, the above step 202 may include the following steps 2021 to 2023:

[0061] Step 2021, obtaining the overflow area.

[0062] The overflow area is the peak area of ​​the portion where the waveform of the chromatogram of the sample to be tested is higher than the waveform of the chromatogram of the standard sample.

[0063] Step 2022, obtaining the peak area of ​​the standard sample.

[0064] The standard sample peak area is the peak area of ​​the standard sample chromatogram waveform.

[0065] Step 2023, determining whether the overflow area does not exceed a preset proportion of the standard sample peak area.

[0066] If it exceeds, quantitative analysis cannot be performed. If it does not exceed, quantitative analysis can be performed. For example, it can be determined whether the overflow area does not exceed 20% of the standard sample peak area.

[0067] In summary, through steps 2021 to 2023, it can be determined whether the chromatogram of the sample to be tested can be quantitatively analyzed.

[0068] Step 203: in response to the chromatogram of the sample to be tested being unable to be quantitatively analyzed, the chromatogram of the sample to be tested is corrected using the chromatogram of the standard sample.

[0069] Compare the peak shape of the chromatogram of the sample to be tested with the peak shape of the chromatogram of the standard sample. Correct the portion of the waveform of the chromatogram of the sample to be tested that is higher than the waveform of the chromatogram of the standard sample to correct it to the waveform of the chromatogram of the standard sample in the corresponding portion. Figure 6 , Figure 6 Correct the upper curved part of the circle to the lower curved part.

[0070] After testing, the above method is used, such as Figure 6 The sample chromatogram shown above can be corrected to Figure 6 In the chromatogram shown below, the matrix interference of the uncorrected peak is particularly obvious. After the peak shape is corrected, the interference factor can be effectively removed, which shows that the above method can effectively suppress the matrix interference factor. The difference in the calculated peak area of ​​the matrix interference peak before and after correction is shown in Table 1 below:

[0071] Table 1

[0072] Internal standard peak area Has interference peak area Corrected peak area 434602.114 338725.054 402402.213 453807.710 327041.522 412705.630 437100.198 316050.716 405204.103 466514.415 330396.845 423917.355 442858.819 316202.337 409938.213

[0073] By comparing the corrected data and the interference peak area data in the third column of the table, it can be concluded that the chromatogram processing method in this embodiment can effectively improve the accuracy of matrix interference peaks.

[0074] As a possible implementation, the method further includes:

[0075] Step 204: in response to the chromatogram of the sample to be tested meeting the basic requirements of the quantitative analysis, the chromatogram of the standard sample is used to suppress matrix interference on the chromatogram of the sample to be tested.

[0076] For the chromatogram of the sample to be tested that meets the basic requirements of the quantitative analysis, the analysis accuracy of the chromatogram of the sample to be tested can be further improved by using a processing method similar to step 203. Therefore, similar to step 203, for the chromatogram of the sample to be tested that meets the basic requirements of the quantitative analysis, the part of the waveform of the chromatogram of the sample to be tested that is higher than the waveform of the chromatogram of the standard sample can also be corrected to the waveform of the chromatogram of the standard sample in the corresponding part.

[0077] In summary, the present application can evaluate whether those chromatograms that may contain matrix interference are suitable for quantitative calculation by comparing known standard sample chromatograms. By correcting and eliminating the interference information of the matrix on the chromatographic peak, the accuracy of the quantitative process can be improved. In addition, the present application can automatically identify and remove the matrix peak, and more accurately obtain the chromatographic peak shape information of the analyte, so as to be better applied to quantitative analysis and the calculation of the standard curve.

[0078] See also Figure 7 , which is a chromatogram processing device provided in an embodiment of the present application, the device 700, comprises: an acquisition module 701, a judgment module 702 and a correction module 703;

[0079] Wherein, the acquisition module 701 is used to obtain the chromatogram of the standard sample and the chromatogram of the sample to be tested;

[0080] A judgment module 702 is used to judge whether the chromatogram of the sample to be tested can be quantitatively analyzed by using the chromatogram of the standard sample;

[0081] The correction module 703 is used to correct the chromatogram of the sample to be tested by using the chromatogram of the standard sample in response to the chromatogram of the sample to be tested being unable to be quantitatively analyzed.

[0082] As a possible implementation manner, the device 700 further includes:

[0083] The interference suppression module 704 is used to suppress matrix interference on the chromatogram of the sample to be tested by using the chromatogram of the standard sample in response to the chromatogram of the sample to be tested meeting the basic requirements of the quantitative analysis.

[0084] As a possible implementation, the determination module 702 includes:

[0085] A first area acquisition unit is used to acquire the overflow area, where the overflow area is the peak area of ​​the portion where the waveform of the chromatogram of the sample to be tested is higher than the waveform of the chromatogram of the standard sample;

[0086] A second area acquisition unit, used to acquire a standard sample peak area, wherein the standard sample peak area is a peak area of ​​a chromatogram waveform of the standard sample;

[0087] The judging unit is used to judge whether the area of ​​the overflow portion does not exceed a preset proportion of the peak area of ​​the standard sample.

[0088] As a possible implementation, the correction module 703 includes:

[0089] The correction unit is used to correct the chromatogram of the sample to be tested by using the chromatogram of the standard sample in response to the area of ​​the overflow portion exceeding a preset proportion of the peak area of ​​the standard sample.

[0090] As a possible implementation manner, the correction unit includes:

[0091] The correction component is used to correct the part of the chromatogram waveform of the sample to be tested that is higher than the waveform of the chromatogram waveform of the standard sample to the waveform of the chromatogram waveform of the standard sample in the corresponding part.

[0092] As a possible implementation, the interference suppression module 704 includes:

[0093] The interference suppression unit is used to correct the part of the chromatogram waveform of the sample to be tested that is higher than the waveform of the chromatogram waveform of the standard sample to the waveform of the chromatogram waveform of the standard sample in the corresponding part.

[0094] See also Figure 8 , this figure is a structural diagram of a chromatogram processing device provided in an embodiment of the present application, and the device includes: a memory 801 and a processor 802.

[0095] Memory 801: used to store program codes and transmit the program codes to the processor.

[0096] Processor 802: used to execute the steps of the above chromatogram processing method according to the instructions in the program code.

[0097] In addition, the present application also provides a computer-readable storage medium, in which computer instructions are stored. When the computer instructions are executed on a chromatogram processing device, the chromatogram processing device executes the steps of the above-mentioned chromatogram processing method.

[0098] It should be noted that each embodiment in this specification is described in a progressive manner, and the same or similar parts between the embodiments can be referred to each other, and each embodiment focuses on the differences from other embodiments. In particular, for the device embodiment, since it is basically similar to the method embodiment, the description is relatively simple, and the relevant parts can be referred to the partial description of the method embodiment. The device embodiment described above is merely schematic, in which the unit described as a separate component may or may not be physically separated, and the component prompted as a unit may or may not be a physical unit, that is, it may be located in one place, or it may be distributed on multiple network units. Some or all of the modules can be selected according to actual needs to achieve the purpose of the scheme of this embodiment. Ordinary technicians in this field can understand and implement it without paying creative work.

[0099] The above is only a specific implementation of the present application, but the protection scope of the present application is not limited thereto. Any changes or substitutions that can be easily thought of by a person skilled in the art within the technical scope disclosed in the present application should be included in the protection scope of the present application. Therefore, the protection scope of the present application should be based on the protection scope of the claims.

Claims

1. A chromatogram processing method, characterized in that: The method comprises: Obtaining a chromatogram of a standard sample and a chromatogram of a sample to be tested, wherein the chromatograms are: Using the standard sample chromatogram, determining whether the sample chromatogram to be tested can be quantitatively analyzed; In response to the chromatogram of the sample to be tested being unable to be quantitatively analyzed, the chromatogram of the sample to be tested is corrected using the chromatogram of the standard sample.

2. The method according to claim 1, characterized in that The method further comprises: In response to the chromatogram of the sample to be tested meeting the basic requirements of the quantitative analysis, the chromatogram of the standard sample is used to suppress matrix interference on the chromatogram of the sample to be tested.

3. The method according to claim 1, characterized in that The step of using the standard sample chromatogram to determine whether the chromatogram of the sample to be tested can be quantitatively analyzed includes: Obtaining the overflow area, wherein the overflow area is the peak area of ​​the portion where the waveform of the chromatogram of the sample to be tested is higher than the waveform of the chromatogram of the standard sample; Obtaining a standard sample peak area, wherein the standard sample peak area is a peak area of ​​a chromatogram waveform of the standard sample; It is determined whether the area of ​​the overflow portion does not exceed a preset proportion of the peak area of ​​the standard sample.

4. The method according to claim 3, characterized in that In response to the chromatogram of the sample to be tested being unable to be quantitatively analyzed, the chromatogram of the sample to be tested is corrected using the chromatogram of the standard sample, comprising: In response to the overflow portion area exceeding a preset ratio of the standard sample peak area, the chromatogram of the sample to be tested is corrected using the standard sample chromatogram.

5. The method according to claim 1 or 4, characterized in that: The method of using the standard sample chromatogram to calibrate the sample chromatogram to be tested comprises: The portion of the chromatogram waveform of the sample to be tested that is higher than the waveform of the chromatogram waveform of the standard sample is corrected to the waveform of the chromatogram waveform of the standard sample at the corresponding portion.

6. The method according to claim 2, characterized in that The method of using the standard sample chromatogram to suppress matrix interference on the chromatogram of the sample to be tested comprises: The portion of the chromatogram waveform of the sample to be tested that is higher than the waveform of the chromatogram waveform of the standard sample is corrected to the waveform of the chromatogram waveform of the standard sample at the corresponding portion.

7. A chromatogram processing device, characterized in that: The device comprises: An acquisition module, used for acquiring a chromatogram of a standard sample and a chromatogram of a sample to be tested; A judgment module, used to judge whether the chromatogram of the sample to be tested can be quantitatively analyzed by using the chromatogram of the standard sample; The correction module is used for correcting the chromatogram of the sample to be tested by using the chromatogram of the standard sample in response to the chromatogram of the sample to be tested being unable to be quantitatively analyzed.

8. The device according to claim 7, characterized in that The device also includes: The interference suppression module is used to suppress matrix interference of the chromatogram of the sample to be tested by using the chromatogram of the standard sample in response to the chromatogram of the sample to be tested meeting the basic requirements of the quantitative analysis.

9. A chromatogram processing device, characterized in that: The device comprises: a memory and a processor; The memory is used to store program codes and transmit the program codes to the processor; The processor is used to execute the steps of the chromatogram processing method according to any one of claims 1 to 6 according to the program code.

10. A computer-readable storage medium, characterized in that: The computer-readable storage medium stores a computer program. When the computer program runs on a chromatogram processing device, the chromatogram processing device performs the steps of chromatogram processing according to any one of claims 1 to 6.

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