Method and device for determining MRM ion pair, electronic equipment and storage medium

Abstract

The invention relates to the field of liquid chromatography and mass spectrometry methods, and provides a method and device for determining an MRM ion pair, electronic equipment and a storage medium. The method for determining the MRM ion pair comprises the following steps: inputting known information of a mixture into a prediction model to obtain predicted parent ions and predicted fragment ions of each substance in the mixture output by the prediction model, and obtaining a measurement instrument to perform single sampling and measurement on the mixture, obtaining a plurality of chromatographic peaks and actually measured parent ions and actually measured fragment ions corresponding to each chromatographic peak; matching the predicted parent ions with the actually measured parent ions, and matching the predicted fragment ions with the actually measured fragment ions; a target substance and an MRM ion pair corresponding to the target substance are determined, the target substance is a substance successfully matched with one of the chromatographic peaks, and the MRM ion pair comprises actually measured parent ions and actually measured fragment ions. Therefore, the MRM ion pairs of various substances in the mixture can be determined through single measurement on the mixture, and the measurement efficiency is improved.

Description

TECHNICAL FIELD

[0001] The present application belongs to the field of liquid mass analysis methods, and particularly relates to a method and device for determining MRM ion pairs, an electronic device, and a storage medium. BACKGROUND

[0002] In the development process of liquid mass analysis methods, it is necessary to establish a liquid mass quantitative method to determine multiple reaction monitoring (MRM) ion pairs of multiple standard samples. The existing detection method needs to sample and measure each standard sample (substance) respectively to determine the MRM ion pair of each standard sample, and the measurement efficiency is low. SUMMARY

[0003] Therefore, the embodiments of the present application provide a method and device for determining MRM ion pairs, an electronic device, and a storage medium, which can improve the measurement efficiency of MRM ion pairs of multiple substances.

[0004] A first aspect of the embodiments of the present application provides a method for determining MRM ion pairs, comprising: inputting known information of a mixture into a prediction model to obtain predicted parent ions and predicted fragment ions of each substance in the mixture output by the prediction model, wherein the known information comprises an identification of each of the substances, a molecular weight of each of the substances, and a measurement parameter of a measurement instrument; obtaining multiple chromatographic peaks and measured parent ions and measured fragment ions corresponding to each of the chromatographic peaks obtained by single sampling and measurement of the mixture by the measurement instrument; matching the predicted parent ions and the measured parent ions, and matching the predicted fragment ions and the measured fragment ions; determining a target substance and an MRM ion pair corresponding to the target substance, wherein the target substance is a substance successfully matched with one of the chromatographic peaks, the successful matching of the target substance with the chromatographic peak means that the predicted parent ions are matched with the corresponding measured parent ions, and the predicted fragment ions are matched with the corresponding measured fragment ions, and the MRM ion pair comprises the measured parent ions and the measured fragment ions.

[0005] In an embodiment, the prediction model further outputs predicted chromatographic peak retention times corresponding to each of the substances under preset chromatographic conditions, and after matching the predicted parent ions and the measured parent ions, and matching the predicted fragment ions and the measured fragment ions, the method further comprises: if there are more than one substance successfully matched with the chromatographic peaks, obtaining measured chromatographic peak retention times corresponding to the multiple chromatographic peaks obtained by the measurement instrument measuring the mixture; According to the predicted chromatographic peak retention time and the measured chromatographic peak retention time, a corresponding MRM ion pair of each of the substances is determined.

[0006] In an embodiment, after the predicted parent ions and the measured parent ions are matched, and the predicted fragment ions and the measured fragment ions are matched, the method further comprises: If there is a case that the predicted parent ions and the measured parent ions are matched, and the predicted fragment ions and the measured fragment ions are not matched, the predicted fragment ions corresponding to the substances are updated to the measured fragment ions.

[0007] In an embodiment, the predicted parent ions and the corresponding measured parent ions are matched, which means that the difference between the mass-to-charge ratios of the predicted parent ions and the corresponding measured parent ions is within a preset error range; the predicted fragment ions and the corresponding measured fragment ions are matched, which means that the similarity between the secondary mass spectra of the predicted fragment ions and the corresponding measured fragment ions is greater than a preset value.

[0008] In an embodiment, the measuring instrument is a liquid chromatograph-mass spectrometer.

[0009] In an embodiment, the measuring instrument is a liquid chromatograph-mass spectrometer. The measuring instrument is instructed to perform full scanning according to a scanning range, and the scanning range covers the signal range of each of the predicted parent ions. When the signal of the measured parent ion exceeding a preset threshold is scanned, the measuring instrument is instructed to trigger secondary fragment scanning to determine the corresponding measured fragment ion.

[0010] In an embodiment, after the predicted parent ions and the measured parent ions are matched, and the predicted fragment ions and the measured fragment ions are matched, the method further comprises: According to the number of target substances, a matching success rate is output.

[0011] A second aspect of the embodiments of the present application provides a device for determining MRM ion pairs, comprising: A prediction module is configured to input known information of a mixture into a prediction model, to obtain predicted parent ions and predicted fragment ions of each substance in the mixture output by the prediction model, and the known information comprises an identifier of each of the substances, a molecular weight of each of the substances, and a measurement parameter of a measuring instrument. A measurement module is configured to acquire a plurality of chromatographic peaks and corresponding measured parent ions and measured fragment ions of each of the chromatographic peaks obtained by single sampling and measurement of the mixture by the measuring instrument. a matching module configured to match the predicted parent ions and the measured parent ions, and match the predicted fragment ions and the measured fragment ions; a determining module configured to determine a target substance and an MRM ion pair corresponding to the target substance, the target substance being a substance matched successfully with one of the chromatographic peaks, the target substance being matched successfully with the chromatographic peak indicating that the predicted parent ions and the corresponding measured parent ions are matched, and the predicted fragment ions and the corresponding measured fragment ions are matched, the MRM ion pair including the measured parent ions and the measured fragment ions corresponding to the target substance.

[0012] A third aspect of the embodiments of the present application provides an electronic device, including a memory, a processor, and a computer program stored in the memory and executable on the processor, and the processor implements the method for determining an MRM ion pair according to the first aspect.

[0013] A fourth aspect of the embodiments of the present application provides a computer readable storage medium, which stores a computer program, and the computer program is executable by a processor to implement the method for determining an MRM ion pair according to the first aspect.

[0014] A fifth aspect of the embodiments of the present application provides a computer program product, which, when executed on an electronic device, causes the electronic device to perform the method for determining an MRM ion pair according to any one of the first aspect.

[0015] Compared with the prior art, the embodiments of the present application have the beneficial effects that: the known information of the mixture is input into a prediction model to obtain predicted parent ions and predicted fragment ions of each substance in the mixture output by the prediction model, and then a measuring instrument is used to perform single sampling and measurement on the mixture to obtain a plurality of chromatographic peaks and measured parent ions and measured fragment ions corresponding to each chromatographic peak. The predicted parent ions and the measured parent ions are matched, and the predicted fragment ions and the measured fragment ions are matched. According to a target substance matched successfully with each chromatographic peak, a target substance and an MRM ion pair corresponding to the target substance are determined. The target substance is matched successfully with the chromatographic peak, indicating that the predicted parent ions and the corresponding measured parent ions are matched, and the predicted fragment ions and the corresponding measured fragment ions are matched. Therefore, the target substance matched successfully with the chromatographic peak indicates that the substance corresponding to the chromatographic peak is the target substance, and the measured parent ions and the measured fragment ions corresponding to the chromatographic peak are the measured parent ions and the measured fragment ions of the target substance. The measured parent ions and the measured fragment ions are the MRM ion pair. Therefore, by performing single measurement on the mixture, the MRM ion pairs corresponding to a plurality of substances in the mixture can be determined, and the measurement efficiency is improved compared with measuring each substance respectively. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of this application, the accompanying drawings used in the description of the embodiments or the prior art will be briefly introduced below.

[0017] Figure 1 This is a schematic diagram illustrating the implementation flow of a method for determining MRM ion pairs provided in an embodiment of this application; Figure 2 This is a schematic diagram of the prediction information output by the prediction model provided in the embodiments of this application; Figure 3 This is a schematic diagram of matching chromatographic peaks provided in an embodiment of this application; Figure 4 This is a schematic diagram of an apparatus for determining MRM ion pairs provided in an embodiment of this application; Figure 5 This is a schematic diagram of the structure of the electronic device provided in the embodiments of this application. Detailed Implementation

[0018] In the following description, specific details such as particular system architectures and techniques are set forth for illustrative purposes and not for limitation, in order to provide a thorough understanding of the embodiments of this application. However, those skilled in the art will understand that this application may also be implemented in other embodiments without these specific details. In other instances, detailed descriptions of well-known systems, apparatuses, circuits, and methods have been omitted so as not to obscure the description of this application with unnecessary detail.

[0019] It should be understood that, when used in this specification and the appended claims, the term "comprising" indicates the presence of the described features, integrals, steps, operations, elements and / or components, but does not exclude the presence or addition of one or more other features, integrals, steps, operations, elements, components and / or collections thereof.

[0020] It should also be understood that the terminology used in this specification is for the purpose of describing particular embodiments only and is not intended to limit the scope of the application. As used in this specification and the appended claims, the singular forms “a,” “an,” and “the” are intended to include the plural forms unless the context clearly indicates otherwise.

[0021] It should also be further understood that the term “and / or” as used in this application specification and the appended claims means any combination of one or more of the associated listed items and all possible combinations, and includes such combinations.

[0022] As used in the present specification and the accompanying claims, the term “if’ can be interpreted as meaning “when,” or “upon,” or “in response to a determination,” or “in response to a detection” depending on the context. Similarly, the phrase “if it is determined” or “if [the recited condition or event] is detected” can be interpreted as meaning “upon determining” or “in response to a determining” or “upon detecting [the recited condition or event]” or “in response to a detection of [the recited condition or event],” depending on the context.

[0023] The method for determining MRM ion pairs provided in the present application is exemplarily described below.

[0024] A liquid chromatography-mass spectrometry (LC-MS) method is used to detect target substances in a liquid. Before the LC-MS method is applied to routine substance testing or scientific research, the analysis method needs to be developed and verified. For example, when establishing an LC-MS method in a laboratory, all analysis steps (such as mass spectrometry conditions, chromatography conditions, sample pretreatment, etc.) in the analysis method need to be optimized during the development process to ensure that the established analysis method can detect the target substance. Before the LC-MS method is applied to actual substance detection and scientific research, the analysis method also needs to be strictly and comprehensively verified to ensure that the performance of the analysis method meets the requirements and to ensure the accuracy and reliability of the detection results.

[0025] The conventional process for establishing an LC-MS method at least includes the following steps. First, the target substance to be detected is determined, and a standard substance including the target substance is prepared. Then, the mass spectrometry method and the liquid chromatography method used to detect the target substance are determined. The mass spectrometry method includes determining the MRM ion pair of the target substance and optimizing the mass spectrometry parameters used in the mass spectrometry method. The liquid chromatography method includes determining the chromatographic retention time of the target substance, determining the chromatographic column, determining the mobile phase, and optimizing the peak separation degree, etc. After the mass spectrometry method and the liquid chromatography method are determined, the pretreatment method needed when detecting the target substance in the sample also needs to be determined to remove the interfering substances in the sample. After the LC-MS method is initially determined, the LC-MS method also needs to be verified, including the verification of accuracy, precision, and the verification of matrix effect and linear range.

[0026] The method for determining MRM ion pairs provided in the embodiments of the present application is mainly used to determine the MRM ion pairs of target substances. In the development process of the LC-MS method, the MRM ion pairs of multiple target substances need to be determined. In the prior art, the MRM ion pairs of each target substance need to be detected respectively, and the detection frequency is high and the detection efficiency is low. The method for determining MRM ion pairs provided in the embodiments of the present application can obtain the MRM ion pairs of multiple target substances through single detection of a mixture including the multiple target substances, thereby improving the detection efficiency.

[0027] Please refer to the accompanying drawings Figure 1The method for determining an MRM ion pair provided in an embodiment of the present application comprises the following steps: S101: inputting known information of a mixture into a prediction model to obtain predicted parent ions and predicted fragment ions of each substance in the mixture output by the prediction model, wherein the known information comprises an identity of each substance, a molecular weight of each substance, and a measurement parameter of a measurement instrument.

[0028] The mixture refers to a substance obtained by mixing a plurality of substances. For example, the mixture is a mixture of caffeine and benzoic acid, or a mixture of glucose, cholesterol, creatine, vitamins, etc.

[0029] The prediction model is obtained by pre-training a machine learning algorithm. For example, the training sample comprises an identity of each substance in the mixture, a molecular weight of each substance, a measurement parameter of a measurement instrument, and parent ions and fragment ions corresponding to each substance. The training sample is input into a machine learning model, the machine learning model searches a human metabolome database (HMDB), METLIN, etc., to obtain ion information of each substance, and trains the machine learning model according to the ion information of each substance, the molecular weight of each substance, the measurement parameter of the measurement instrument, and the parent ions and fragment ions corresponding to each substance, so as to optimize the parameters of the machine learning model. The machine learning model after optimization is the prediction model.

[0030] The identity of the substance can be the name, number, or digital identifier (for example, CAS number) of the substance. The measurement parameter of the measurement instrument refers to the relevant parameter of the measurement instrument when measuring the measured parent ions and measured fragment ions in the mixture. For example, the measurement instrument comprises a liquid chromatograph, and the measurement parameters comprise a column model, a mobile phase composition, and a chromatographic gradient during the measurement process of the liquid chromatograph.

[0031] In addition to the identity of each substance, the molecular weight of each substance, and the measurement parameter of the measurement instrument, the known information can also comprise known parent ions and fragment ions of part of the substances, so as to improve the prediction accuracy of the prediction model.

[0032] S102: obtaining a plurality of chromatographic peaks and measured parent ions and measured fragment ions corresponding to each chromatographic peak obtained by single sampling and measurement of the mixture by the measurement instrument.

[0033] Specifically, a plurality of substances to be measured are mixed to obtain a mixture. The mixture enters the measurement instrument through a sample injector, the measurement instrument measures the mixture, and outputs a plurality of chromatographic peaks, each chromatographic peak corresponding to a measured parent ion and a measured fragment ion.

[0034] In an embodiment, the measuring instrument is a liquid chromatography tandem mass spectrometer (e.g., a triple quadrupole liquid chromatography mass spectrometer or a quadrupole tandem flight tube liquid chromatography mass spectrometer), which includes a liquid chromatography system and a mass spectrometry detection system. After the mixture enters the liquid chromatography tandem mass spectrometer, the mixture first enters the liquid chromatography system, which includes a chromatographic column. The plurality of substances in the mixture are separated in the chromatographic column according to differences in polarity and interactions. The separated substances sequentially flow out of the liquid chromatography column and enter the mass spectrometry detection system. For each substance, the mass spectrometry detection system ionizes the substance to obtain charged ions, performs a first mass spectrometry (MS1) scan on the charged ions, and obtains a measured parent ion corresponding to each substance. After obtaining the measured parent ion, the mass spectrometry detection system collides the measured parent ion, and performs a second mass spectrometry (MS2) scan on the collided ions to obtain a measured ion fragment corresponding to the measured parent ion.

[0035] The first mass spectrometry scan is mainly to quickly obtain the mass-to-charge ratio (m / z) and signal intensity of all ions in the sample, so as to determine the molecular weight or preliminarily screen the components. The second mass spectrometry scan focuses on structural analysis, generates a daughter ion spectrum by selecting a specific parent ion for fragmentation (such as electron activated dissociation technology), and then analyzes the specific chemical structure according to the spectrum.

[0036] In an embodiment, after determining the predicted parent ions in the mixture, the measuring instrument is instructed to perform a full scan according to a scan range, so that the scan range covers the signal range of each predicted parent ion, so that the signals corresponding to all predicted parent ions can be detected, and the measurement accuracy of the measuring instrument is improved. For example, after ionizing the substance, the mass analyzer in the measuring instrument is instructed to perform a full scan according to a scan range, so that the scan range covers the signal range of each predicted parent ion. When the measuring instrument scans a signal of a measured parent ion that exceeds a preset threshold, it is determined that the measured parent ion is detected, the measuring instrument is instructed to collide the measured parent ion, and a secondary fragment (second mass spectrometry) scan is triggered, and the corresponding measured fragment ion is determined according to the scan result. The detection accuracy is improved by determining the measured parent ion and the measured fragment ion in the above information-dependent manner.

[0037] It can be understood that if the substances in the mixture have the same charge (positive or negative), the mixture only needs to be injected into the measuring instrument once, and the measured parent ion and the measured fragment ion corresponding to each chromatographic peak can be measured. If the substances in the mixture have different charges, the mixture needs to be injected into the measuring instrument twice to measure each substance with different charges.

[0038] S103: match the predicted parent ion and the measured parent ion, and match the predicted fragment ion and the measured fragment ion.

[0039] Specifically, for each chromatographic peak, the measured parent ion corresponding to the chromatographic peak and each predicted parent ion are matched to obtain a predicted parent ion matched with the measured parent ion. If the predicted parent ion is matched with the measured parent ion, it is further determined whether the predicted ion fragment of the predicted parent ion and the measured ion fragment of the measured parent ion are matched. If the predicted parent ion is matched with the measured parent ion, and the predicted ion fragment of the predicted parent ion and the measured ion fragment of the measured parent ion are matched, it is determined that the substance corresponding to the chromatographic peak and the substance corresponding to the predicted parent ion are possibly the same. If the predicted parent ion is not matched with the measured parent ion, it is determined that there is no predicted parent ion matched with the chromatographic peak, that is, the substance corresponding to the chromatographic peak cannot be determined.

[0040] In an embodiment, the matching of the predicted parent ion and the corresponding measured parent ion means that the difference between the mass-to-charge ratios of the predicted parent ion and the corresponding measured parent ion is within a preset error range. The matching of the predicted fragment ion and the corresponding measured fragment ion means that the similarity of the secondary spectrum of the predicted fragment ion and the corresponding measured fragment ion is greater than a preset value. The horizontal coordinate of the secondary spectrum is the mass-to-charge ratio, and the vertical coordinate is the relative abundance of each fragment ion. The similarity of the secondary spectrum of the predicted fragment ion and the corresponding measured fragment ion being greater than the preset value means that the predicted fragment ion and the measured fragment ion are the same.

[0041] S104: determining a target substance and an MRM ion pair corresponding to the target substance, the target substance being the substance matched successfully with one of the chromatographic peaks.

[0042] The MRM ion pair includes the measured parent ion and the measured fragment ion corresponding to the target substance. The successful matching of the target substance with one of the chromatographic peaks means that the predicted parent ion of the target substance is matched with the measured parent ion corresponding to one of the chromatographic peaks, and the predicted fragment ion of the target substance is matched with the measured fragment ion corresponding to the chromatographic peak. That is, for any target substance, only one chromatographic peak is matched successfully with the target substance, and the chromatographic peak is the chromatographic peak of the target substance. The MRM ion pair of the target substance is the MRM ion pair corresponding to the chromatographic peak.

[0043] After obtaining each chromatographic peak, if there is only one target substance matched successfully with each chromatographic peak, that is, the chromatographic peak and the target substance are one-to-one, the MRM ion pairs of all substances in the mixture can be obtained. If only part of the chromatographic peaks have only one target substance matched successfully, the MRM ion pairs of part of the substances in the mixture can be obtained. Compared with measuring each substance respectively to obtain the corresponding MRM ion pair, the measurement efficiency is improved.

[0044] In an embodiment, after matching the predicted parent ions and the measured parent ions, and matching the predicted fragment ions and the measured fragment ions, the substances that are successfully matched with each chromatographic peak are determined. For any substance, if there is only one chromatographic peak that is successfully matched with the substance, the substance is determined as the target substance, and the MRM ion pair of the chromatographic peak that is successfully matched with the target substance is the MRM ion pair of the target substance. For any substance, if there are multiple chromatographic peaks that are successfully matched with the substance, the chromatographic peak that is successfully matched with the substance is determined by failing the matching or by further determining the chromatographic peak that is successfully matched with the substance by other conditions.

[0045] In another embodiment, the prediction model further outputs the predicted chromatographic peak retention time of each substance under the preset chromatographic condition. For any substance, if there is more than one chromatographic peak that is successfully matched with the substance, the measured chromatographic peak retention time of each chromatographic peak obtained by measuring the mixture by the measuring instrument is obtained, and the MRM ion pair corresponding to each substance is determined according to the predicted chromatographic peak retention time and the measured chromatographic peak retention time. Specifically, for any substance, the chromatographic peak retention time can be the time interval from injecting the mixture into the measuring instrument to detecting the chromatographic peak of the substance by the measuring instrument, or can be the arrangement order of the time interval in all time intervals corresponding to the substances. For any substance, if there is more than one chromatographic peak that is successfully matched with the substance, the chromatographic peak corresponding to the measured chromatographic peak retention time that is consistent with the predicted chromatographic peak retention time of the substance is further determined from the more than one chromatographic peak, and the MRM ion pair corresponding to the chromatographic peak is determined as the MRM ion pair of the substance, and the measured chromatographic peak retention time corresponding to the chromatographic peak is determined as the chromatographic peak retention time of the target substance. After determining the target substance and the MRM ion pair corresponding to the target substance, the target substance, the MRM ion pair corresponding to the target substance, and the chromatographic peak retention time of the target substance can be output simultaneously.

[0046] It can be understood that, after matching the predicted parent ions and the measured parent ions, and matching the predicted fragment ions and the measured fragment ions, and determining the chromatographic peak that is uniquely matched with the substance, the matching result can also be verified according to the predicted chromatographic peak retention time and the measured chromatographic peak retention time. For any substance, if there is a chromatographic peak that is uniquely matched with the substance, and the predicted chromatographic peak retention time corresponding to the substance is consistent with the measured chromatographic peak retention time corresponding to the chromatographic peak, the MRM ion pair of the substance is determined as the MRM ion pair of the chromatographic peak.

[0047] In one embodiment, after matching the predicted parent ions and the measured parent ions, and matching the predicted fragment ions and the measured fragment ions, if there is a match between the predicted parent ions and the measured parent ions, and there is no match between the predicted fragment ions and the measured fragment ions, the predicted fragment ions of the corresponding substance are updated to the measured fragment ions. For any chromatographic peak, if the measured parent ions match one of the predicted parent ions, and the measured chromatographic peak retention time is consistent with the corresponding predicted chromatographic peak retention time, and there is no match between the predicted fragment ions and the measured fragment ions, the predicted fragment ions are updated to the measured fragment ions, the MRM ion pair of the chromatographic peak is taken as the MRM ion pair of the substance matched with the chromatographic peak, and the prediction model is corrected according to the measured fragment ions.

[0048] For example, the prediction model outputs the parent ions, the fragment ions and the predicted chromatographic peak retention time of six substances. As shown in the following table. Figure 2 The predicted parent ion of substance A is A1, the predicted fragment ion is A2, the predicted parent ion of substance B is B1, the predicted fragment ion is B2, the predicted parent ion of substance C is C1, the predicted fragment ion is C2, the predicted parent ion of substance D is D1, the predicted fragment ion is D2, the predicted parent ion of substance E is E1, the predicted fragment ion is E2, the predicted parent ion of substance F is F1, and the predicted fragment ion is F2. The size relationship of the predicted chromatographic peak retention time of each substance is A < C < D < E < F < B.

[0049] As shown in the following table. Figure 3As shown, the measurement instrument measures 10 chromatographic peaks, and the labels of the 10 chromatographic peaks are 1, 2, 3, 4, 5, 6, 7, 8, 9 and 10 in the order of the retention time of the measured chromatographic peak from small to large. According to the predicted parent ions of each substance output by the prediction model, the predicted parent ion matched with the measured parent ion of each chromatographic peak is determined in sequence. Through the matching, the measured parent ion of chromatographic peak 1 is Z1, it is determined that there is no predicted parent ion matched with chromatographic peak 1, the predicted parent ion matched with chromatographic peak 2 is A1, the predicted parent ion matched with chromatographic peak 3 is A1, the predicted parent ion matched with chromatographic peak 4 is C1, the predicted parent ion matched with chromatographic peak 5 is D1, the predicted parent ion matched with chromatographic peak 6 is F1, the predicted parent ion matched with chromatographic peak 7 is B1, the predicted parent ion matched with chromatographic peak 8 is E1, the predicted parent ion matched with chromatographic peak 9 is F1, and the predicted parent ion matched with chromatographic peak 10 is B1. For the chromatographic peak matched with the predicted parent ion, the measured fragment ion and the predicted fragment ion are further matched. Through the matching, the measured fragment ion and the predicted fragment ion of chromatographic peak 2 are the same, and chromatographic peak 2 is uniquely matched with substance A, so it is determined that chromatographic peak 2 is the chromatographic peak of substance A; the measured fragment ion and the predicted fragment ion of chromatographic peak 4 are the same, and chromatographic peak 4 is uniquely matched with substance C, so it is determined that chromatographic peak 4 is the chromatographic peak of substance C; the measured fragment ion and the predicted fragment ion of chromatographic peak 5 are the same, and chromatographic peak 4 is uniquely matched with substance D, so it is determined that chromatographic peak 5 is the chromatographic peak of substance D; the measured fragment ion and the predicted fragment ion of chromatographic peak 8 are the same, and chromatographic peak 8 is uniquely matched with substance E, so it is determined that chromatographic peak 8 is the chromatographic peak of substance E; the measured fragment ion and the predicted fragment ion of chromatographic peak 10 are the same, and chromatographic peak 10 is uniquely matched with substance B, so it is determined that chromatographic peak 10 is the chromatographic peak of substance B. Chromatographic peak 6 and chromatographic peak 9 are both successfully matched with substance F, so according to the predicted chromatographic peak retention time of substance F, it can be seen that the predicted chromatographic peak retention time of substance F is between the predicted chromatographic peak retention time of substance E and the predicted chromatographic peak retention time of substance B, and then it is determined that chromatographic peak 9 is the chromatographic peak of substance F. According to the chromatographic peak corresponding to each substance, the MRM ion pair and the chromatographic peak retention time of each substance can be determined.

[0050] In an embodiment, after obtaining the target substance matched with the chromatographic peak successfully, the matching success rate is determined according to the number of target substances and the total number of substances in the mixture, and the matching success rate is output, so as to facilitate subsequent improvement of the prediction model.

[0051] In the above embodiment, by inputting known information of the mixture into the prediction model, predicted parent ions and predicted fragment ions of each substance in the mixture output by the prediction model are obtained, and then a single sampling and measurement of the mixture by a measuring instrument is performed to obtain a plurality of chromatographic peaks and measured parent ions and measured fragment ions corresponding to each chromatographic peak. The predicted parent ions and the measured parent ions are matched, and the predicted fragment ions and the measured fragment ions are matched; target substances matched with all or part of the plurality of chromatographic peaks are obtained, and the MRM ion pair of the chromatographic peak is taken as the MRM ion pair of the target substance. Therefore, by performing a single measurement on the mixture, the MRM ion pair corresponding to each substance in the mixture can be determined, and the measurement efficiency is improved relative to measuring each substance separately. The above method can be applied to the development process of liquid chromatography-mass spectrometry analysis method, which can significantly shorten the method development time and reduce manual work.

[0052] It should be understood that the size of the serial number of each step in the above embodiment does not mean the order of execution, and the execution order of each process should be determined according to its function and internal logic, and should not constitute any limitation on the implementation process of the embodiments of the present application.

[0053] Corresponding to the method for determining the MRM ion pair described in the above embodiment, Figure 4 A structural block diagram of the device for determining the MRM ion pair provided by the embodiments of the present application is shown, and only parts related to the embodiments of the present application are shown for ease of illustration.

[0054] As Figure 4 shown, the device for determining the MRM ion pair includes a prediction module 41, a measurement module 42, a matching module 43, and a determination module 44.

[0055] The prediction module 41 is configured to input known information of a mixture into a prediction model to obtain predicted parent ions and predicted fragment ions of each substance in the mixture output by the prediction model, and the known information includes an identification of each substance, a molecular weight of each substance, and a measurement parameter of a measuring instrument; The measurement module 42 is configured to obtain a plurality of chromatographic peaks and measured parent ions and measured fragment ions corresponding to each chromatographic peak obtained by performing a single sampling and measurement of the mixture by the measuring instrument; The matching module 43 is configured to match the predicted parent ions and the measured parent ions, and match the predicted fragment ions and the measured fragment ions; The determining module 44 is configured to determine a target substance and an MRM ion pair corresponding to the target substance, the target substance being a substance successfully matched with one of the chromatographic peaks, the target substance being successfully matched with the chromatographic peak indicating that the predicted parent ion and the corresponding measured parent ion are matched, and the predicted fragment ion and the corresponding measured fragment ion are matched, the MRM ion pair including the measured parent ion and the measured fragment ion corresponding to the target substance.

[0056] In an embodiment, the prediction model further outputs a predicted chromatographic peak retention time corresponding to each of the substances under preset chromatographic conditions, and the matching module 43 is further configured to: if there are more than one substance successfully matched with one of the chromatographic peaks, obtaining measured chromatographic peak retention times corresponding to the plurality of chromatographic peaks obtained by measuring the mixture by the measuring instrument; determining an MRM ion pair corresponding to each of the substances according to the predicted chromatographic peak retention time and the measured chromatographic peak retention time.

[0057] In an embodiment, the matching module 43 is further configured to: if there is a case where the predicted parent ion and the measured parent ion are matched, and the predicted fragment ion and the measured fragment ion are not matched, updating the predicted fragment ion corresponding to the substance to the measured fragment ion.

[0058] In an embodiment, the predicted parent ion and the corresponding measured parent ion are matched, indicating that the difference between the mass-to-charge ratio of the predicted parent ion and the corresponding measured parent ion is within a preset error range; and the predicted fragment ion and the corresponding measured fragment ion are matched, indicating that the similarity of the secondary spectrum of the predicted fragment ion and the corresponding measured fragment ion is greater than a preset value.

[0059] In an embodiment, the measuring instrument is a liquid chromatograph-mass spectrometer.

[0060] In an embodiment, the measuring module 42 is further configured to: instructing the measuring instrument to perform full scanning according to a scanning range, the scanning range covering the signal range of each of the predicted parent ions; when the signal of the measured parent ion exceeding a preset threshold is scanned, instructing the measuring instrument to trigger secondary fragment scanning to determine the corresponding measured fragment ion.

[0061] In an embodiment, the determining module 44 is further configured to: outputting a matching success rate according to the number of the target substances.

[0062] It should be noted that the information interaction, execution process and the like between the above apparatuses / units are based on the same concept as the method embodiments of the present application, and the specific functions and brought technical effects can be referred to the method embodiments part, which will not be repeated here.

[0063] Figure 5 is a structural schematic diagram of an electronic device provided by the embodiment of the present application. The electronic device can be a desktop computer, a notebook computer, a palm computer, a cloud server and the like computing device.

[0064] As shown in Figure 5 , the electronic device of the embodiment includes a processor 51, a memory 52, and a computer program 53 stored in the memory 52 and executable on the processor 51. The processor 51 implements the steps in the method embodiments for determining MRM ion pairs when executing the computer program 53, such as Figure 1 steps S101-S104. Alternatively, the processor 51 implements the functions of the modules / units in each of the above apparatus embodiments when executing the computer program 53, such as Figure 4 the functions of the prediction module 41 to the determination module 44.

[0065] For example, the computer program 53 can be divided into one or more modules / units, which are stored in the memory 52 and executed by the processor 51 to complete the present application. The one or more modules / units can be a series of computer program instruction segments capable of completing a specific function, which are used to describe the execution process of the computer program 53 in the electronic device.

[0066] Those skilled in the art can understand, Figure 5 is only an example of an electronic device and does not constitute a limitation on the electronic device, which can include more or fewer components than shown, or combine certain components, or different components, for example, the electronic device can also include an input / output device, a network access device, a bus and the like.

[0067] The processor 51 can be a central processing unit (CPU), and can also be other general-purpose processors, a digital signal processor (DSP), an application specific integrated circuit (ASIC), a field-programmable gate array (FPGA) or other programmable logic devices, discrete gate or transistor logic devices, discrete hardware components, etc. The general-purpose processor can be a microprocessor or the processor can also be any conventional processor.

[0068] The memory 52 can be an internal storage unit of the electronic device, such as a hard disk or a memory of the electronic device. The memory 52 can also be an external storage device of the electronic device, such as a plug-in hard disk, a smart media card (SMC), a secure digital (SD) card, a flash card, etc. Further, the memory 52 can include both the internal storage unit and the external storage device of the electronic device. The memory 52 is used to store the computer program and other programs and data required by the electronic device. The memory 52 can also be used to temporarily store data that has been output or will be output.

[0069] Those skilled in the art can clearly understand that, for the convenience and brevity of description, only the division of the above functional units and modules is exemplified, and in actual application, the above functions can be completed by different functional units and modules according to needs, that is, the internal structure of the apparatus is divided into different functional units or modules to complete all or part of the above described functions. Each functional unit and module in the embodiment can be integrated in one processing unit, or each unit can exist physically, or two or more units can be integrated in one unit, and the integrated unit can be realized in the form of hardware or in the form of software functional unit. In addition, the specific names of each functional unit and module are only for easy distinction, and do not limit the protection scope of the present application. The specific working process of the units and modules in the above system can refer to the corresponding process in the foregoing method embodiments, which will not be described here.

[0070] In the above embodiments, the description of each embodiment has its own emphasis, and the parts not described or recorded in detail in a certain embodiment can be referred to the relevant description of other embodiments.

[0071] In the embodiments of the present disclosure, it should be understood that the disclosed apparatus / equipment and method can be implemented in other manners. For example, the described apparatus / equipment embodiments are merely schematic. Taking the division of the modules or units as an example, the division can be changed in actual implementation, for example, a plurality of units or components can be combined or integrated into another system, or some features can be ignored or not executed. In addition, the displayed or discussed mutual couplings or direct couplings or communication connections can be indirect couplings or communication connections through some interfaces, devices or units, and can be in electrical, mechanical or other forms.

[0072] The units described as separate components can or can not be physically separate, and the components shown as units can or can not be physical units, i.e., can be located in one place, or can be distributed on a plurality of network units. Some or all of the units can be selected according to actual needs to achieve the purpose of the embodiments.

[0073] In addition, each functional unit in each embodiment of the present disclosure can be integrated in one processing unit, or each unit can be physically present separately, or two or more units can be integrated in one unit. The integrated unit can be realized in the form of hardware or in the form of a software functional unit.

[0074] If the integrated module / unit is realized in the form of a software functional unit and sold or used as an independent product, it can be stored in a computer readable storage medium. Based on this understanding, all or part of the flow of the above-mentioned embodiment methods can also be completed by a computer program instructing related hardware, and the computer program can be stored in a computer readable storage medium. When the processor executes the computer program, the steps of each method embodiment described above can be implemented. The computer program includes computer program code, which can be in the form of source code, object code, executable file or some intermediate form. The computer readable medium can include any entity or device capable of carrying the computer program code, recording medium, U disk, mobile hard disk, magnetic disk, optical disk, computer memory, read-only memory (ROM), random access memory (RAM), electrical carrier signal, telecommunication signal and software distribution medium, etc. Those skilled in the art can understand that the units and algorithm steps of each example described in combination with the embodiments disclosed herein can be realized in electronic hardware or a combination of computer software and electronic hardware. Whether the functions are realized in hardware or software manner depends on the specific application and design constraints of the technical solution. The skilled person can use different methods to realize the described functions for each specific application, but such implementation should not be considered beyond the scope of the present application.

[0075] The above-described embodiments are only used to illustrate the technical solutions of the present application, but not limit the technical solutions; although the present application has been described in detail with reference to the foregoing embodiments, those skilled in the art should understand that the technical solutions recorded in the foregoing embodiments can still be modified, or some technical features can be replaced by equivalent replacements; and these modifications or replacements do not make the essence of the corresponding technical solutions deviate from the spirit and scope of the technical solutions of the embodiments of the present application, and should be included in the protection scope of the present application.

Claims

1. A method for determining MRM ion pairs, characterized in that, include: The known information of the mixture is input into the prediction model to obtain the predicted parent ion and predicted fragment ion of each substance in the mixture output by the prediction model. The known information includes the identifier of each substance, the molecular weight of each substance, and the measurement parameters of the measuring instrument. The measuring instrument performs a single sampling and measurement of the mixture, resulting in multiple chromatographic peaks and the measured parent ion and fragment ion corresponding to each chromatographic peak; The predicted precursor ion and the measured precursor ion are matched, and the predicted fragment ion and the measured fragment ion are matched; Identify the target substance and the corresponding MRM ion pair. The target substance is the substance that successfully matches one of the chromatographic peaks. Successful matching of the target substance with the chromatographic peak means that the predicted precursor ion matches the corresponding measured precursor ion, and the predicted fragment ion matches the corresponding measured fragment ion. The MRM ion pair includes the measured precursor ion and the measured fragment ion.

2. The method for determining MRM ion pairs according to claim 1, characterized in that, The prediction model also outputs the predicted chromatographic peak retention times for each substance under preset chromatographic conditions. After matching the predicted precursor ion with the measured precursor ion and matching the predicted fragment ion with the measured fragment ion, the method further includes: If a substance is found that matches more than one of the chromatographic peaks, the measured retention times of the multiple chromatographic peaks corresponding to the chromatographic peaks obtained by the measuring instrument from the mixture are obtained. Based on the predicted chromatographic peak retention time and the measured chromatographic peak retention time, the MRM ion pair corresponding to each substance is determined.

3. The method for determining MRM ion pairs according to claim 1, characterized in that, After matching the predicted precursor ion with the measured precursor ion, and matching the predicted fragment ion with the measured fragment ion, the method further includes: If there is a match between the predicted precursor ion and the measured precursor ion, but a mismatch between the predicted fragment ion and the measured fragment ion, the predicted fragment ion for the corresponding substance will be updated to the measured fragment ion.

4. The method for determining MRM ion pairs according to claim 1, characterized in that, The matching of the predicted precursor ion and the corresponding measured precursor ion means that the difference in the mass-to-charge ratio between the predicted precursor ion and the corresponding measured precursor ion is within a preset error range; the matching of the predicted fragment ion and the corresponding measured fragment ion means that the similarity of the secondary spectra of the predicted fragment ion and the corresponding measured fragment ion is greater than a preset value.

5. The method for determining MRM ion pairs according to claim 1, characterized in that, The measuring instrument is a liquid chromatography-tandem mass spectrometer.

6. The method for determining MRM ion pairs according to claim 1, characterized in that, The method further includes acquiring multiple chromatographic peaks and the measured precursor ion and fragment ion corresponding to each chromatographic peak obtained by the measuring instrument performing a single sampling and measurement of the mixture, and the method also includes: The measuring instrument is instructed to perform a full scan according to a scanning range that covers the signal range of each of the predicted precursor ions; When a signal of the measured precursor ion exceeding a preset threshold is detected, the measuring instrument is instructed to trigger a secondary fragment scan to determine the corresponding measured fragment ion.

7. The method for determining MRM ion pairs according to claim 1, characterized in that, After matching the predicted precursor ion with the measured precursor ion, and matching the predicted fragment ion with the measured fragment ion, the method further includes: The matching success rate is output based on the quantity of the target substance.

8. An apparatus for determining MRM ion pairs, characterized in that, include: The prediction module is used to input known information about the mixture into the prediction model to obtain the predicted parent ion and predicted fragment ion of each substance in the mixture output by the prediction model. The known information includes the identifier of each substance, the molecular weight of each substance, and the measurement parameters of the measuring instrument. The measurement module is used to acquire multiple chromatographic peaks obtained by the measuring instrument in a single sampling and measurement of the mixture, and the measured parent ion and measured fragment ion corresponding to each chromatographic peak; A matching module is used to match the predicted precursor ion with the measured precursor ion, and to match the predicted fragment ion with the measured fragment ion. The determination module is used to determine the target substance and the corresponding MRM ion pair. The target substance is a substance that successfully matches one of the chromatographic peaks. The successful matching of the target substance with the chromatographic peak means that the predicted precursor ion matches the corresponding measured precursor ion, and the predicted fragment ion matches the corresponding measured fragment ion. The MRM ion pair includes the measured precursor ion and the measured fragment ion corresponding to the target substance.

9. An electronic device comprising a memory, a processor, and a computer program stored in the memory and executable on the processor, characterized in that, When the processor executes the computer program, it implements the method for determining MRM ion pairs as described in any one of claims 1 to 7.

10. A computer-readable storage medium storing a computer program, characterized in that, When the computer program is executed by a processor, it implements the method for determining MRM ion pairs as described in any one of claims 1 to 7.

Images