CN110596278A - Metabolite liquid chromatography-mass spectrometry combined detection method - Google Patents
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Abstract
The invention discloses a metabolite liquid chromatogram-mass spectrum combined detection method, which comprises the steps of firstly detecting a sample to be detected on a computer; importing a standard product detection database file; preparing the first detection result off-line data of a sample to be detected; preparing DP and CE combined gradient information; setting a peak height threshold; exporting DP and CE optimization results; and establishing a DP and CE optimized database according to the optimized detection result. The invention greatly reduces the time consumed by optimizing condition analysis and groping of the conventional DPCE project, accurately monitors the sample collection condition by taking the 2-chlorophenylalanine as an internal standard, and monitors the fluctuation state of the instrument by taking 17 mixed standards as quality control products.
Description
Technical Field
The invention belongs to the technical field of substance detection, and particularly relates to a metabolite liquid chromatography-mass spectrometry combined detection method.
Background
Metabolomics is a discipline that resembles genomics and proteomics, and performs large-throughput qualitative and quantitative analysis of metabolites in organisms, and thus finds out the interrelations of individual metabolites with each other.
In the detection by using a liquid chromatography-mass spectrometry combined system, because of the uncertain performance of the content of substances in a sample, the phenomenon that the content of the sample is too high to exceed the detection threshold of equipment often occurs. The detection substance threshold is adjusted to be within the effective detection range by adjusting the Declustering Potential (DP) and Collision Energy (CE) of each target substance. Adjusting DP, CE not only needs the operator to have better practical experience, still need the manual work to carry out a large amount of data processing, the combination, very consuming time and power, especially when high flux sample detects, the experiment all needs 3 ~ 4 hours consuming time to carry out data analysis on average at every turn, and need many times to repeat the experiment verification, until finding DP, CE optimization combination condition, in addition, artifical data analysis makes mistakes easily, cause the experiment to fail repeatedly, consequently, how to carry out DP, CE combination optimization fast effectually, even realize can directly reachd best DP through the experiment of many times repeatedly, CE combination is the problem that prior art is urgent to solve.
Disclosure of Invention
This section is for the purpose of summarizing some aspects of embodiments of the invention and to briefly introduce some preferred embodiments. In this section, as well as in the abstract and the title of the invention of this application, simplifications or omissions may be made to avoid obscuring the purpose of the section, the abstract and the title, and such simplifications or omissions are not intended to limit the scope of the invention.
The present invention has been made in view of the above-mentioned technical drawbacks.
Therefore, as one aspect of the invention, the invention overcomes the defects in the prior art and provides a metabolite liquid chromatography-mass spectrometry combined detection method.
In order to solve the technical problems, the invention provides the following technical scheme: a metabolite liquid chromatography-mass spectrometry combined detection method comprises the following steps,
detecting a sample to be detected on a computer for the first time;
importing a standard product detection database file;
preparing the first detection result off-line data of a sample to be detected;
preparing DP and CE combined gradient information;
setting a peak height threshold;
exporting DP and CE optimization results;
and establishing a DP and CE optimized database according to the optimized detection result.
As a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: and importing the standard product detection database file, wherein the DP and CE information of the standard product detection database file is imported.
As a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: and preparing the first detection result off-line data of the sample to be detected, wherein the first detection result off-line data comprises the original off-line integral result data of the first on-line mass spectrum detection.
As a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: and preparing DP and CE combined gradient information, wherein the DP and CE combined gradient information is given according to the standard detection database file.
As a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: and establishing the DP and CE optimized database according to the optimized detection result, wherein the optimal DP and CE conditions can be directly selected according to the DP and CE optimized database without repeated experimental verification.
As a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: the method also comprises the steps that 2-chlorophenylalanine is used as an internal standard instead of a solvent, and the collection condition of an actual sample is reflected through the peak area and retention time of the 2-chlorophenylalanine in the detection process; the concentration of the 2-chlorophenylalanine is 1 mu g/mL.
As a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: and the method also comprises the steps of using a mixed standard sample of 4, 4' -methylenebis (2-chloroaniline), p-anisidine, L-tyrosine methyl ester, 3-chloroaniline, 2, 4-dimethylquinoline, sulfapyridine, atrazine, sulfadoxine, DL-leucine, N-benzoyl-L-tyrosine ethyl ester, 6-phenyl-2-thiouracil, N- (o-toluoyl) glycine, 2-methyl-5-nitroimidazole-1-ethanol, glycyrrhetinic acid, flavanone, epsilon-caprolactone and 2-aminopyridine as a quality control material, detecting at least two pins of the quality control material each time, and analyzing the state of the detector according to the overlapping condition of spectrograms.
As a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: the 4, 4' -methylene bis (2-chloroaniline) is prepared from the following components in percentage by mass: p-anisidine: l-tyrosine methyl ester: 3-chloroaniline: 2, 4-dimethylquinoline: sulfapyridine: atrazine: sulfadoxine: DL-leucine: N-benzoyl-L-tyrosine ethyl ester: 6-phenyl-2-thiouracil: n- (o-toluoyl) glycine: 2-methyl-5-nitroimidazole-1-ethanol: glycyrrhetinic acid: flavanone: epsilon-caprolactone: 2-aminopyridine ═ 1: 0.5: 0.5: 2: 1: 0.4: 0.1: 0.1: 0.2: 0.5: 0.5: 1: 1: 0.1: 0.5: 2: 0.2.
as a preferred scheme of the metabolite liquid chromatography-mass spectrometry combined detection method provided by the invention: the concentration of the 4, 4' -methylene-bis (2-chloroaniline) is 1 mu g/mL, the concentration of p-anisidine is 0.5 mu g/mL, the concentration of L-tyrosine methyl ester is 0.5 mu g/mL, the concentration of 3-chloroaniline is 2 mu g/mL, the concentration of 2, 4-dimethylquinoline is 1 mu g/mL, the concentration of sulfapyridine is 0.4 mu g/mL, the concentration of atrazine is 0.1 mu g/mL, the concentration of sulfadoxine is 0.1 mu g/mL, the concentration of DL-leucine is 0.2 mu g/mL, the concentration of N-benzoyl-L-tyrosine ethyl ester is 0.5 mu g/mL, the concentration of 6-phenyl-2-thiouracil is 0.5 mu g/mL, the concentration of N- (o-toluoyl) glycine is 1 mu g/mL, and the concentration of p-anisidine is 0.5 mu g/mL, The concentration of 2-methyl-5-nitroimidazole-1-ethanol is 1 mug/mL, the concentration of glycyrrhetinic acid is 0.1 mug/mL, the concentration of flavanone is 0.5 mug/mL, the concentration of epsilon-caprolactone is 2 mug/mL, and the concentration of 2-aminopyridine is 0.2 mug/mL.
The invention has the beneficial effects that: the method greatly reduces the time consumed by analyzing and groping the optimization conditions of the DPCE of the conventional project, the time consumed by analyzing the optimization adjustment data of the DPCE parameter of the previous single substance is about 3 to 4 hours, the step is omitted by the optimization adjustment of the DPCE of the single project after the method is used, the optimal DP and CE conditions can be directly selected according to the DP and CE optimization database, and the data analysis is not required to be carried out manually; the method and the device automatically generate the files required by subsequent operation, avoid errors possibly caused by manual processing, and ensure the accuracy and the effectiveness of results. When data processing is carried out, the DPCE1 interface tool records, summarizes and builds a library for peak height substances appearing in the project, so that data query can be conveniently carried out under the same condition in the later period, and the purpose of data accumulation and use is achieved. The method is used for carrying out automation from screening of abnormal results of mass spectrum detection peak value overhigh to establishment of new DP and CE optimization conditions for secondary detection and verification, and errors caused by manual operation are avoided; the DPCE optimization results detected in the project are sorted and stored, DPCE optimization conditions can be directly judged according to database information, and experimental verification is not needed. The invention takes 2-chlorophenylalanine as an internal standard to accurately monitor the sample collection condition, and adopts 17 mixed standards as quality control substances to monitor the fluctuation state of the instrument, thereby greatly shortening the data analysis and time, realizing the accurate monitoring of the adopted process and the instrument fluctuation and improving the experimental efficiency of the liquid chromatogram-mass spectrum tandem detection.
Drawings
In order to more clearly illustrate the technical solutions of the embodiments of the present invention, the drawings needed to be used in the description of the embodiments will be briefly introduced below, and it is obvious that the drawings in the following description are only some embodiments of the present invention, and it is obvious for those skilled in the art to obtain other drawings based on these drawings without inventive exercise. Wherein:
FIG. 1 is a DPCE optimized step1 interface diagram according to the present invention.
FIG. 2 is a DPCE optimized step2 interface diagram according to the present invention.
FIG. 3 is an exemplary parameter setting of the MultiQuant software of the method of the present invention.
FIG. 4 is a diagram showing the appearance of peaks in a LC-MS/MS apparatus of the quality control product of the present invention.
FIG. 5 is a diagram showing the overlapping of peaks of the quality control substance of the present invention on a liquid chromatography-mass spectrometer.
FIG. 6 is a chromatogram of a conventional mixing method in one experiment.
Detailed Description
In order to make the aforementioned objects, features and advantages of the present invention comprehensible, embodiments accompanied with examples are described in detail below.
In the following description, numerous specific details are set forth in order to provide a thorough understanding of the present invention, but the present invention may be practiced in other ways than those specifically described and will be readily apparent to those of ordinary skill in the art without departing from the spirit of the present invention, and therefore the present invention is not limited to the specific embodiments disclosed below.
Furthermore, reference herein to "one embodiment" or "an embodiment" means that a particular feature, structure, or characteristic described in connection with the embodiment is included in at least one implementation of the invention. The appearances of the phrase "in one embodiment" in various places in the specification are not necessarily all referring to the same embodiment, nor are separate or alternative embodiments mutually exclusive of other embodiments.
The invention adopts the ultra-high performance liquid chromatography-triple quadrupole/linear ion TRAP tandem mass spectrometry (UPLC-QTRAP) technology, and the mass spectrometer is AB Sciex Q-TRAP 6500.
The metabolite liquid chromatogram-mass spectrum combined detection method comprises a step of detecting a sample to be detected on a computer for the first time; importing a standard product detection database file; preparing off-line data of a first detection result of a sample to be detected; preparing DP and CE combined gradient information; setting a peak height threshold value; exporting DP and CE optimization results; and establishing a DP and CE optimized database according to the optimized detection result.
The standard substance detection database file is a liquid chromatography-mass spectrometry combined detection database of a standard substance to be detected, and comprises DP and CE optimization information and information of the substance to be detected.
The DP and CE combined gradient information is the DP and CE data of the standard detection database so as to give a combined gradient. The peak height threshold is set according to the mass spectrometer sensitivity.
The present invention creates two web-version interface tools, including DPCE optimized step1 (FIG. 1) and DPCE optimized step2 (FIG. 2). The DPCE optimization step1 is mainly used for processing the off-machine result of the first detection of the sample, the DPCE optimization step2 is used for processing the verification result of the subsequent experimental detection except the first detection, and a DP and CE optimization database is established according to the step 2.
After the step of importing a standard product detection database file, the step of preparing a first detection result off-line data of a sample to be detected, the step of preparing DP and CE combined gradient information and the step of setting a peak height threshold, the DPCE optimization step1 displays and counts the information of the input file and exports DP and CE optimization result data. The imported data are divided into positive and negative ions with qualified peak heights and positive and negative ions with unqualified peak heights in the result data, and meanwhile, the unqualified positive and negative ions and related item information are sorted and exported, wherein the item information comprises item types and dates and is used for subsequent data statistics. And if the experimental data are qualified, only positive and negative ion information with qualified peak height is derived. And if the substances with the peak heights being too high exist, establishing new on-machine data for the substances with the peak heights being unqualified according to the on-machine detection format of the experiment by utilizing the previously prepared DP and CE combined conditions, and using the on-machine data for subsequent on-machine detection and verification of the experiment.
After the computer is detected and verified, result data are imported, DP and CE combination conditions are updated, an input file button of a DPCE optimization step2 interface is clicked to input the files, then database files corresponding to projects are imported, corresponding database types are selected, and the result data are processed by a back-end program, wherein the method comprises the following steps: 1. re-screening substances with unqualified peak heights in the verification result, and generating a new on-machine format file by combining the updated DP and CE combination conditions; 2. screening and extracting the substances with qualified peak heights in the verification result, and sorting and merging the project number, the first DP and CE conditions and the corresponding peak height value in the sample, the qualified DP and CE conditions after secondary detection and the corresponding peak height value and the current date into DP and CE optimized database files in a back-end server; when the related substance is detected again, the condition that the peak height value is close to the abnormal peak height value is inquired through the result recorded in the database, and the corresponding DP and CE parameters when the detection is qualified are directly selected, so that the DP and CE conditions of the substance do not need to be verified by experiments again.
The method greatly reduces the time consumed by analyzing and groping the optimization conditions of the DPCE of the conventional project, the time consumed by analyzing the optimization adjustment data of the DPCE parameter of the previous single substance is about 3 to 4 hours, the step is omitted by the optimization adjustment of the DPCE of the single project after the method is used, the optimal DP and CE conditions can be directly selected according to the DP and CE optimization database, and the data analysis is not required to be carried out manually; the invention automatically generates the files required by subsequent operation, avoids errors possibly caused by manual processing and ensures the accuracy and the validity of results. When data processing is carried out, the DPCE1 interface tool records, summarizes and builds a library for peak height substances appearing in the project, so that data query can be conveniently carried out under the same condition in the later period, and the purpose of data accumulation and use is achieved. The method is used for carrying out automation from screening of abnormal results of mass spectrum detection peak value overhigh to establishment of new DP and CE optimization conditions for secondary detection and verification, and errors caused by manual operation are avoided; the DPCE optimization results detected in the project are sorted and stored, DPCE optimization conditions can be directly judged according to database information, and experimental verification is not needed.
In order to monitor the influence of the sample collection condition on the experimental result in the detection process, the invention selects 2-chlorophenylalanine as an internal standard, water is used as a solvent to prepare an internal standard extracting solution of 1 microgram/mL, the internal standard 2-chlorophenylalanine extracting solution is used for replacing a pure organic solvent to extract the experimental sample, the concentration of the internal standard in each sample is ensured to be consistent, data are collected by a computer, in the data collection process, the internal standard peak area and the retention time are checked through the parameter setting of MultiQuant software, the collection condition of the actual sample and the individual sample with abnormal internal standard are reflected through the collection condition of the internal standard, the corresponding collected data are opened to check, and the data are recovered again when the data are abnormal.
Setting parameters of MultiQuant software: deleting substances other than the internal standard; generating a result table of all sample internal standards; selecting one column of area, clicking the creates a metric plot to generate an area line graph, changing the longitudinal coordinate of the line graph into a percentage form, adding a horizontal line representing the average value of the area of the internal standard, enabling the area of the internal standard of the sample to be within 10% of the average value RSD, considering that the sample data collection is normal, returning the sample data collection software to check the sample collection data after the sample data exceeds 10%, and resubmitting the collection of the abnormal sample; and selecting one retention time column, clicking the creates a metric plot to generate a retention time line graph, checking sample collection data by return data collection software with the deviation exceeding 0.1, and resubmitting and collecting abnormal samples.
The invention selects 1 mug/mL 2-chlorophenylalanine water solution as internal standard through repeated screening from a plurality of substances, finds that the internal standard can generate peak and has good peak type under positive and negative ion modes, and the interference to the substance to be measured in the sample is not easy to generate, the method of the invention can accurately monitor the collection condition of the sample, and no omission occurs, and the method is suitable for detecting samples such as serum, urine, tissues, cells and the like as internal standard quality control products, for example, when the detection sample is mixed with air bubbles in the sample adding process, the volume of the sample is reduced, the peak response is reduced, so that the final quantification of the sample is inaccurate, and the technical problem that the prior art method cannot monitor is solved, the peak-out response of the internal standard added into the sample is also reduced, so that the sample with poor collection condition can be accurately found. The method only needs one 2-chlorophenylalanine aqueous solution as an internal standard to replace the original organic solvent of the sample, utilizes the parameter setting function of software, can quickly judge the collection condition of the sample through the peak area and retention time of the internal standard, and is simple, easy to operate and low in cost.
When other substances are selected as the internal standard, such as tyrosine-3-iodide, pentadecafluorooctanoic acid, sucralose, 3-chloroaniline, tridecanoic acid, glycine, benzoic acid, succinic acid, etc., they are not suitable for the internal standard because they are unstable, or they have too large difference in the positive and negative ion modes, or the sample substances are liable to interfere with each other, and the reproducibility of detection is not good.
FIG. 3 shows the parameter settings of the MultiQuant software of the method of the present invention. As can be seen from figure 3, the invention adopts the low-concentration aqueous solution of 1 mug/mL 2-chlorophenylalanine as the internal standard, the chromatographic peak area RSD of repeated experiments is less than 3%, and the repeatability is very good.
In order to monitor whether the running state of the instrument is normal or not in the detection process, the invention adopts the ultra-high performance liquid chromatography-triple quadrupole/linear ion TRAP tandem mass spectrometry (UPLC-QTRAP) technology, the mass spectrometer is AB Sciex Q-TRAP 6500, the analysis software is Multi Quant, the quality control product for metabonomics detection of the invention consists of 17 mixed standards which are screened, the solvent of the 17 mixed standards is 70% methanol water, and the 17 standard samples and the use final concentration thereof of the quality control product are shown in Table 1:
TABLE 1
The invention is suitable for detecting human urine, serum, tissue, cell and other samples, taking human serum as an example, and the conditions of liquid mass spectrometry of 17 mixed standard detections are as follows: the solvents for 17 mixed standard substances are: 70% aqueous methanol; a chromatographic column: c18 filler, column brand Wates ACQUITY HSS T3, i.d. 2.1X 100mm,1.8 um; mobile phase A is 0.04% acetic acid/ultrapure water; mobile phase B: 0.04% acetic acid/acetonitrile; column temperature: 40 ℃; flow rate: 0.35 ml/min; sample introduction amount: 1 uL; the mobile phase gradient was as follows:
mass spectrum conditions: the mass spectrum parameter information is as follows:
the ion pair information is:
the same chromatographic conditions are adopted, 10 times of independent experiments are used for verifying the quality control stability of the 17 mixed standard quality control products and the traditional method for mixing the samples to be tested in the prior art, and three groups of experiments are set in each independent experiment: the 17 mixed standard quality control article groups, the traditional sample mixing method group and the reserpine reference group are respectively provided with 4 repeated detections, and the 17 mixed standard quality control article groups, the traditional sample mixing method group and the reserpine reference group of each independent experiment are respectively provided with 4 repeated detections. The traditional sample mixing method group adopts equal-volume mixing of serum samples of 50 healthy people, a single drug reserpine is used as a reference substance, the chromatographic peak areas of 4 repeated detections of a test sample are calculated in 4 repeated detections of each independent experiment, if the RSD of the chromatographic peak area is within 10%, the test state of the detection process of the test sample is stable, the repeatability is good, if the RSD is within 10% -20%, the stability is general, if the RSD is greater than 20%, the RSD is unstable and the repeatability is poor, and the experimental results are shown in the following table:
in 10 experiments, the RSD of the reference reserpine is within 10% in 4 repeated tests of each experiment, which indicates that the instrument state is stable in the reserpine detection section (the reserpine retention time is about 1.5 min); meanwhile, the RSD of the 17 mixed standard quality control product groups is within 10%, and the retention time of the 17 mixed standard quality control products is dispersed in 0-11 min, so that the instrument state of the retention time of 0-11 min is stable in the 10 experiments.
In one of the independent experiments, the peak area RSD detected by 4 repeated serum samples of the traditional sample mixing method group is more than 20%, the retention time is dispersed in 0.5-6.5 min, and on the data surface, in the experiment, the state of the instrument is stable in the segment of the retention time of 0.5-6.5 min, but the RSD is more than 20% and the experiment repeatability is poor by adopting the traditional sample mixing method, the chromatogram of the traditional sample mixing method of the experiment is shown in figure 6, and through analysis, the mixed sample quality control product of the traditional sample mixing method group is degraded due to the serum samples, so the repeatability is poor, and therefore, although the state of the instrument is stable at the moment, the RSD of the traditional sample mixing method group is more than 20% and the experiment repeatability is poor. At this time, whether the RSD is greater than 20% according to the conventional sample mixing method set or the sample itself is not determined accurately. The quality control method adopting the 17 mixed-standard quality control products has the advantages that the 17 substances are stable in property and not easy to degrade, the 17 substances cannot interfere with signals mutually, chromatographic peaks are well separated, and the retention time is dispersed in 0-11 min, so that the method can accurately reflect the running state of an instrument in a detection section, and is suitable for detecting amino acids, nucleic acids, benzene and derivatives thereof, amines, flavonoids, terpenes, alcohols, lactones, pyridine and other substances in samples such as serum, urine and the like with the retention time of 0-11 min (according to the chromatographic conditions, the retention time of the serum and urine samples is within 11 min).
The mass spectrum response of the 17 mixed standard quality control products is between 1 x 10^6 to 3 x 10^7, the mass spectrum response belongs to the optimal response range of a used testing instrument, and the 17 standard sample compounds are stable in structure and not easy to volatilize and deteriorate.
During the data acquisition process, the fluctuation condition of the instrument is judged according to the overlapping condition of the total ion current chromatograms acquired before and after, the instrument is stable if the chromatograms are overlapped well, and the state of the instrument is judged according to the overlapping condition if the chromatograms are not overlapped well, for example, if the retention time is not overlapped, the column pressure or the column temperature is unstable, and if the peak height is not overlapped, the column blockage or the mass spectrum pollution is possible.
The 17 quality control standard samples of the method come from different material classes, can reflect whether the response of the instrument to different classes of materials is stable or not, alternate collection is carried out in the metabonomics data collection process, if the overlapping graphs of the two-needle mixed standard total ion current chromatogram are well overlapped, the instrument is stable, and if the overlapping graphs are not well overlapped, the reason of the instrument instability is preliminarily judged according to the overlapping graph condition. The mixed standard quality control product is very stable, and has the advantages of simple preparation, small dosage and low cost. The quality control product and the quality control method thereof are suitable for metabonomics detection and quality control of mass spectra and chromatograms of urine, blood and the like. Repeated detection for multiple times aiming at different types of substances proves that the quality control product can accurately reflect the instrument state (whether the instrument is stable, the column pressure, whether the column temperature is stable, whether the column is blocked, whether the column is polluted or not) of a chromatograph or a mass spectrometer and the state of a sample to be detected, and the accuracy of judging whether the instrument state is stable or not by the 17 mixed standard quality control products reaches 100 percent through verification of hundreds of experiments.
In conclusion, the time consumed by analyzing and groping the DPCE optimization conditions of the conventional items is greatly reduced, the time consumed by analyzing the DPCE parameter optimization adjustment data of a single substance detection before is about 3-4 hours, the step is omitted by optimizing and adjusting the DPCE of the single item after the method is used, the optimal DP and CE conditions can be directly selected according to the DP and CE optimization database, and the data analysis is not required to be carried out manually; the method and the device automatically generate the files required by subsequent operation, avoid errors possibly caused by manual processing, and ensure the accuracy and the effectiveness of results. When data processing is carried out, the DPCE1 interface tool records, summarizes and builds a library for peak height substances appearing in the project, so that data query can be conveniently carried out under the same condition in the later period, and the purpose of data accumulation and use is achieved. The method is used for carrying out automation from screening of abnormal results of mass spectrum detection peak value overhigh to establishment of new DP and CE optimization conditions for secondary detection and verification, and errors caused by manual operation are avoided; the DPCE optimization results detected in the project are sorted and stored, DPCE optimization conditions can be directly judged according to database information, and experimental verification is not needed. The invention takes 2-chlorophenylalanine as an internal standard to accurately monitor the sample collection condition, and adopts 17 mixed standards as quality control substances to monitor the fluctuation state of the instrument, thereby greatly shortening the data analysis and time, realizing the accurate monitoring of the adopted process and the instrument fluctuation and improving the experimental efficiency of the liquid chromatogram-mass spectrum tandem detection.
It should be noted that the above-mentioned embodiments are only for illustrating the technical solutions of the present invention and not for limiting, and although the present invention has been described in detail with reference to the preferred embodiments, it should be understood by those skilled in the art that modifications or equivalent substitutions may be made on the technical solutions of the present invention without departing from the spirit and scope of the technical solutions of the present invention, which should be covered by the claims of the present invention.
Claims (9)
1. A metabolite liquid chromatography-mass spectrometry combined detection method is characterized in that: comprises the steps of (a) preparing a mixture of a plurality of raw materials,
detecting a sample to be detected on a computer for the first time;
importing a standard product detection database file;
preparing the first detection result off-line data of a sample to be detected;
preparing DP and CE combined gradient information;
setting a peak height threshold;
exporting DP and CE optimization results;
and establishing a DP and CE optimized database according to the optimized detection result.
2. The metabolite liquid chromatography-mass spectrometry detection method of claim 1, wherein: and importing the standard product detection database file, wherein the DP and CE information of the standard product detection database file is imported.
3. The metabolite liquid chromatography-mass spectrometry detection method of claim 1 or 2, wherein: and preparing the first detection result off-line data of the sample to be detected, wherein the first detection result off-line data comprises the original off-line integral result data of the first on-line mass spectrum detection.
4. The metabolite liquid chromatography-mass spectrometry detection method of claim 1 or 2, wherein: and preparing DP and CE combined gradient information, wherein the DP and CE combined gradient information is given according to the standard detection database file.
5. The metabolite liquid chromatography-mass spectrometry detection method of claim 1 or 2, wherein: and establishing the DP and CE optimized database according to the optimized detection result, wherein the optimal DP and CE conditions can be directly selected according to the DP and CE optimized database without repeated experimental verification.
6. The metabolite liquid chromatography-mass spectrometry detection method of claim 1 or 2, wherein: the method also comprises the steps that 2-chlorophenylalanine is used as an internal standard instead of a solvent, and the collection condition of an actual sample is reflected through the peak area and retention time of the 2-chlorophenylalanine in the detection process; the concentration of the 2-chlorophenylalanine is 1 mu g/mL.
7. The metabolite liquid chromatography-mass spectrometry detection method of claim 1 or 2, wherein: and the method also comprises the steps of using a mixed standard sample of 4, 4' -methylenebis (2-chloroaniline), p-anisidine, L-tyrosine methyl ester, 3-chloroaniline, 2, 4-dimethylquinoline, sulfapyridine, atrazine, sulfadoxine, DL-leucine, N-benzoyl-L-tyrosine ethyl ester, 6-phenyl-2-thiouracil, N- (o-toluoyl) glycine, 2-methyl-5-nitroimidazole-1-ethanol, glycyrrhetinic acid, flavanone, epsilon-caprolactone and 2-aminopyridine as a quality control material, detecting at least two pins of the quality control material each time, and analyzing the state of the detector according to the overlapping condition of spectrograms.
8. The metabolite liquid chromatography-mass spectrometry detection method of claim 7, wherein: the 4, 4' -methylene bis (2-chloroaniline) is prepared from the following components in percentage by mass: p-anisidine: l-tyrosine methyl ester: 3-chloroaniline: 2, 4-dimethylquinoline: sulfapyridine: atrazine: sulfadoxine: DL-leucine: N-benzoyl-L-tyrosine ethyl ester: 6-phenyl-2-thiouracil: n- (o-toluoyl) glycine: 2-methyl-5-nitroimidazole-1-ethanol: glycyrrhetinic acid: flavanone: epsilon-caprolactone: 2-aminopyridine ═ 1: 0.5: 0.5: 2: 1: 0.4: 0.1: 0.1: 0.2: 0.5: 0.5: 1: 1: 0.1: 0.5: 2: 0.2.
9. the metabolite liquid chromatography-mass spectrometry detection method of claim 8, wherein: the concentration of the 4, 4' -methylene-bis (2-chloroaniline) is 1 mu g/mL, the concentration of p-anisidine is 0.5 mu g/mL, the concentration of L-tyrosine methyl ester is 0.5 mu g/mL, the concentration of 3-chloroaniline is 2 mu g/mL, the concentration of 2, 4-dimethylquinoline is 1 mu g/mL, the concentration of sulfapyridine is 0.4 mu g/mL, the concentration of atrazine is 0.1 mu g/mL, the concentration of sulfadoxine is 0.1 mu g/mL, the concentration of DL-leucine is 0.2 mu g/mL, the concentration of N-benzoyl-L-tyrosine ethyl ester is 0.5 mu g/mL, the concentration of 6-phenyl-2-thiouracil is 0.5 mu g/mL, the concentration of N- (o-toluoyl) glycine is 1 mu g/mL, and the concentration of p-anisidine is 0.5 mu g/mL, The concentration of 2-methyl-5-nitroimidazole-1-ethanol is 1 mug/mL, the concentration of glycyrrhetinic acid is 0.1 mug/mL, the concentration of flavanone is 0.5 mug/mL, the concentration of epsilon-caprolactone is 2 mug/mL, and the concentration of 2-aminopyridine is 0.2 mug/mL.
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Effective date of registration: 20240109 Address after: Room 01, 2nd Floor, Building C2-1, Building C2, C6, and C7, Wuhan National Bioindustry Base, No. 666 Gaoxin Avenue, Wuhan Donghu New Technology Development Zone, Wuhan, Hubei Province, 430075 Patentee after: Wuhan Mai Tver Biological Technology Co.,Ltd. Address before: 314100 Room 101, D1 Building, Haitian Talent Pioneering Park, Dayun Town, Jiashan County, Jiaxing City, Zhejiang Province Patentee before: JIAXING METWARE METABOLIC BIOLOGICAL TECHNOLOGY Co.,Ltd. |