CN114740125A

CN114740125A - LC-MS-based 10 cardiovascular drug serum detection method and kit

Info

Publication number: CN114740125A
Application number: CN202210520081.2A
Authority: CN
Inventors: 高飞; 海云; 刘林林
Original assignee: Hangzhou Durbrain Medical Inspection Laboratory Co ltd
Current assignee: Hangzhou Durbrain Medical Inspection Laboratory Co ltd
Priority date: 2022-05-12
Filing date: 2022-05-12
Publication date: 2022-07-12

Abstract

The invention discloses a detection kit for 10 cardiovascular drug serums based on LC-MS, which comprises a mixed standard stock solution; the solutes of the 10 mixed standard stock solutions are clopidogrel, rivaroxaban, apixaban, dabigatran, ticagrelor, rosuvastatin, deshydroxyethoxy ticagrelor, atorvastatin, ortho-hydroxy atorvastatin and para-hydroxy atorvastatin respectively. The compounds of the invention have less chromatographic interference peaks, can be separated from a base line, and have strong specificity, good reproducibility and good selectivity; the pretreatment method is simple and easy to operate, saves time and is far superior to the prior art.

Description

LC-MS-based 10 cardiovascular drug serum detection method and kit

Technical Field

The invention belongs to the field of detection methods and kits for serum of 10 cardiovascular drugs based on LC-MS.

Background

The cardiovascular blood concentration is easily influenced by multiple factors such as heredity, food, combined medication and the like, is closely related to curative effect and toxicity, the liver and kidney toxicity and the nervous system damage and infection are caused by overhigh blood concentration, the rejection reaction and the induction of autoimmune diseases are caused by overlow blood concentration, and the rejection reaction after the kidney transplantation is difficult to distinguish from the nephrotoxicity reaction, so the monitoring of the cardiovascular blood concentration has important significance for guiding the clinical reasonable medication.

The currently commonly used methods for measuring the blood concentration of several kinds of medicines such as cardiovascular diseases and the like mainly comprise an enzyme immunoassay method and the like, a high performance liquid chromatography method and an LC-MS/MS method. The enzyme immunoassay method has the problems of cross interference, and the high performance liquid chromatography has the problems of complex pretreatment, large minimum quantitative lower limit, long analysis time, large consumption of organic solvents and the like. Dorota Danielaka et al report a method for simultaneous determination of ticagrelor and its metabolites and atorvastatin and its metabolites in human plasma using a LC-MS method. However, only o-hydroxy atorvastatin is detected in the metabolite of atorvastatin, and an internal standard is added in the pretreatment process, so that each sample needs 10 minutes for collection, and time and labor are wasted. Srinivas REDDY et al report a detection method for determining rivaroxaban in human plasma, which employs complex pretreatment steps such as solid phase extraction, which greatly increases the experimental cost and time.

In summary, the main drawbacks of the prior art processes for the detection of anti-cardiovascular drugs are:

firstly, the cost is high, most of the conventional HPLC-MS/MS methods adopt deuterated and other internal standards to correct matrix effect and other influences, and the cost of the internal standards is high, which can directly cause the high cost of the whole detection process;

secondly, the flux is low, most of the existing methods are one or more medicines for simultaneous determination, but dozens of medicines are rarely involved, so that the detection efficiency is influenced;

thirdly, the sensitivity is low, and the problem that the sensitivity of a plurality of target objects is relatively low exists in the process of simultaneously detecting a plurality of medicines, the detection accuracy is influenced,

fourthly, the analysis time is long, and in the measurement method in the prior art, the LC part analysis time accounts for most of the proportion, so that the medicine detection time is long, and the general analysis time is longer than 5 minutes.

Disclosure of Invention

In order to solve the problems in the prior art, the invention aims to provide a detection method of 10 cardiovascular drug serums based on LC-MS and a kit thereof.

In order to achieve the purpose, the invention adopts the following technical means:

the invention provides a detection kit for 10 kinds of cardiovascular drug serum based on LC-MS (liquid chromatography-mass spectrometry), which comprises a mixed standard stock solution; the mixed standard stock solution is prepared from 10 single standard stock solutions with different concentrations; the solutes of the 10 single-standard stock solutions are clopidogrel, rivaroxaban, apixaban, dabigatran, ticagrelor, rosuvastatin, deshydroxyethoxy ticagrelor, atorvastatin, ortho-hydroxy atorvastatin and para-hydroxy atorvastatin, respectively.

The detection kit also comprises a blank matrix; the blank matrix is human serum filtered;

the detection kit also comprises a precipitator; the precipitant is methanol;

the detection kit further comprises a mobile phase; the mobile phase comprises mobile phase A liquid and mobile phase B liquid;

the mobile phase A liquid is 1mM-5mM ammonium formate aqueous solution containing 0.1% formic acid; the mobile phase B liquid is 1mM-5mM ammonium formate methanol solution containing 0.1% formic acid;

the detection kit also comprises a quality control product; the quality control products comprise high quality control products, medium quality control products and low quality control products;

the second aspect of the invention provides a detection method of a detection kit for 10 kinds of cardiovascular drug serum based on LC-MS, which comprises the following steps:

s1, preparation of mixed standard working solution:

(1) preparation of a single standard stock solution (taking clopidogrel as an example):

weighing 10mg of clopidogrel standard substance, and diluting the standard substance to 10mL by using methanol to obtain 1mg/mL clopidogrel single-standard mother solution; then taking 50 mu L of clopidogrel single-standard mother liquor and diluting the mother liquor to 1mL by using methanol to obtain 49.7250 mu g/mL clopidogrel single-standard stock solution; the preparation process of other single-standard mother liquor is the same as above, and 10 single-standard stock solutions corresponding to the cardiovascular drugs are respectively obtained. In particular, see the following table:

(2) preparation of stock solution (M0)

The preparation method is shown in the following table, and the prepared product is sealed and stored in a refrigerator at the temperature of-80 ℃ for later use.

(3) Preparation of mixed standard working solution

The blank matrix is human serum filtered

Diluting 200. mu.L of M0 with 3800. mu.L of a blank medium to obtain W1, diluting 400. mu.L of W1 with 100. mu.L of a blank medium to obtain W2, diluting 300. mu.L of W1 with 200. mu.L of a blank medium to obtain W3, diluting 300. mu.L of W1 with 300. mu.L of a blank medium to obtain W4, diluting 200. mu.L of W1 with 300. mu.L of a blank medium to obtain W5, diluting 100. mu.L of W1 with 400. mu.L of a blank medium to obtain W6, diluting 100. mu.L of W1 with 900. mu.L of a blank medium to obtain W7, diluting 300. mu.L of W7 with 300. mu.L of a blank medium to obtain W8, diluting 100. mu.L of W7 with 400. mu.L of a blank medium to obtain W9, diluting 50. mu.L of W7 with 450. mu.L of a blank medium to obtain W10, and hermetically storing the mixture at-80 ℃ in a refrigerator;

s2, preparation of quality control products:

respectively taking 50 mu L, 150 mu L and 400 mu L of standard solution W1, fixing the volume to 500 mu L by using a blank matrix, and uniformly mixing to obtain three quality control products of low, medium and high.

S3, processing the sample to be detected:

precisely transferring the biological sample and the blank matrix into a clean centrifugal tube, adding methanol, and performing vortex oscillation for 5 min; and centrifuging for 5 min; and transferring the supernatant to a 96-hole sample injection plate by using a pipette, and placing the 96-hole sample injection plate in the sample injection plate at-20 ℃ for freezing and mass spectrum sample injection.

And S4, detecting the sample to be detected.

The detection method of the detection kit for 10 kinds of cardiovascular drug serum based on LC-MS further comprises the steps of detecting the mixed standard working solution and quality control substances and drawing a standard curve: and taking the peak area of the target object of the mixed standard working solution as the ordinate y of the standard curve graph, and taking the concentration in the mixed standard working solution as the abscissa x of the standard curve graph to obtain a standard curve equation.

The detection conditions of the sample to be detected are as follows:

the chromatographic conditions were as follows:

the mobile phase A liquid is 1mM-5mM ammonium formate aqueous solution containing 0.1% formic acid, and the mobile phase B liquid is 1mM-5mM ammonium formate methanol solution containing 0.1% formic acid;

the flow rate is 0.2-0.4mL/min, the column temperature is 20-40 ℃, and the sample injection is 1-10 mu L;

gradient elution mode is adopted.

Wherein the elution gradient is as follows: at 0-0.3min, the volume of the mobile phase B liquid is 2%; in 0.3-2.0min, the volume of the mobile phase B liquid is increased to 98%; the volume of the mobile phase B liquid is maintained to be 98 percent within 2.0-3.5 min; reducing the volume of the mobile phase B liquid to 2% in 3.6min, and maintaining the volume at 2% to 4.0 min;

tandem-mass spectrometry conditions were as follows:

an ion source: electrospray ion source, positive ion mode; spray capillary voltage: 1.0-3.5 KV; desolventizing gas temperature: 400-500 ℃; desolventizing air flow rate: 800-1000L/Hr; ion source temperature: 130 ℃ and 150 ℃; desolventizing gas pressure: 8 bar; collision gas pressure: 0.7 bar; scanning mode: and (5) monitoring multiple reactions.

Wherein, the quantitative analysis ion pair of the multi-reaction detection is as follows: clopidogrel quantitation ion pair m/z 322.0 → 211.9, rivaroxaban quantitation ion pair m/z 435.0 → 144.8, apixaban quantitation ion pair m/z 460.1 → 443.2, dabigatran quantitation ion pair m/z 472.2 → 289.1, ticagrelor quantitation ion pair m/z523.1 → 152.9, rosuvastatin quantitation ion pair m/z 481.5 → 258.1, deshydroxyethoxy ticagrelor quantitation ion pair m/z 479.1 → 152.9, atorvastatin quantitation ion pair m/z 559.5 → 440.1, orthohydroxy atorvastatin quantitation ion pair m/z 574.9 → 440.1, hydroxyalipivastatin quantitation ion pair m/z 574.7 → 440.2.

The invention has the advantages of

Compared with the prior art, the invention has the following beneficial effects:

the compounds of the invention have less chromatographic interference peaks, can be separated from a base line, and have strong specificity, good reproducibility and good selectivity; the pretreatment method is simple and easy to operate, saves time and is far superior to the prior art.

The invention has fast detection speed, 4.0min detection time and higher detection speed than the prior art, and is suitable for analyzing a large quantity of clinical research samples;

the invention reduces the dosage of organic solvent and further reduces the pollution to the environment.

The invention establishes a detection method of 10 cardiovascular drug serums based on LC-MS and a kit thereof by utilizing LC-MS;

the invention uses the external standard method to solve the problem of high cost.

The invention can accurately quantify by monitoring the AUC of the drug-time curve sampled at two points.

Drawings

Fig. 1 shows the MRM spectrum of clopidogrel standard;

figure 2 shows the MRM spectrum of rivaroxaban standard;

figure 3 shows the MRM spectrum of the apixaban standard;

FIG. 4 shows MRM spectra of dabigatran standard;

figure 5 shows the MRM spectrum of a deshydroxyethoxy ticagrelor standard;

figure 6 shows the MRM spectrum of rosuvastatin standard;

fig. 7 shows an MRM spectrum of a ticagrelor standard;

figure 8 shows an MRM spectrum of atorvastatin standards;

figure 9 shows an MRM spectrum of an orthohydroxy atorvastatin standard;

figure 10 shows MRM spectra for atorvastatin hydroxy standards;

fig. 11 shows a standard graph of clopidogrel;

figure 12 shows a standard graph of rivaroxaban;

figure 13 shows a standard graph of apixaban;

FIG. 14 shows a standard graph of dabigatran;

figure 15 shows a standard graph of deshydroxyethoxyticagrelor;

figure 16 shows a standard curve diagram for rosuvastatin;

fig. 17 shows a standard graph of ticagrelor;

figure 18 shows a standard graph of atorvastatin;

figure 19 shows a standard graph of ortho-hydroxy atorvastatin;

FIG. 20 shows a standard curve for atorvastatin

Detailed Description

Unless otherwise indicated, implied from the context, or customary in the art, all parts and percentages herein are by weight and the testing and characterization methods used are synchronized with the filing date of the present application. Where applicable, the contents of any patent, patent application, or publication referred to in this application are incorporated herein by reference in their entirety, and the equivalent family of patents is also incorporated by reference, in particular for the definitions set forth in these documents regarding synthetic techniques, product and process designs, polymers, comonomers, initiators or catalysts, and the like, in the art. To the extent that a definition of a particular term disclosed in the prior art is inconsistent with any definitions provided herein, the definition of the term provided herein controls.

The numerical ranges in this application are approximations, and thus may include values outside of the ranges unless otherwise specified. A numerical range includes all numbers from the lower value to the upper value, in increments of 1 unit, provided that there is a separation of at least 2 units between any lower value and any higher value. For example, if a compositional, physical, or other property (e.g., molecular weight, melt index, etc.) is recited as 100 to 1000, it is intended that all individual values, e.g., 100, 101, 102, etc., and all subranges, e.g., 100 to 166, 155 to 170, 198 to 200, etc., are explicitly recited. For ranges containing a numerical value less than 1 or containing a fraction greater than 1 (e.g., 1.1, 1.5, etc.), 1 unit is considered to be 0.0001, 0.001, 0.01, or 0.1, as appropriate. For ranges containing single digit numbers less than 10 (e.g., 1 to 5), 1 unit is typically considered 0.1. These are merely specific examples of what is intended to be expressed and all possible combinations of numerical values between the lowest value and the highest value enumerated are to be considered to be expressly stated in this application.

When used with respect to chemical compounds, the singular includes all isomeric forms and vice versa (e.g., "hexane" includes all isomers of hexane, individually or collectively) unless expressly specified otherwise. In addition, unless explicitly stated otherwise, the use of the terms "a", "an" or "the" are intended to include the plural forms thereof.

The terms "comprising," "including," "having," and derivatives thereof do not exclude the presence of any other component, step or procedure, and are not intended to exclude the presence of other elements, steps or procedures not expressly disclosed herein. To the extent that any doubt is eliminated, all compositions herein containing, including, or having the term "comprise" may contain any additional additive, adjuvant, or compound, unless expressly stated otherwise. Rather, the term "consisting essentially of … …" excludes any other components, steps or processes from the scope of any of the terms hereinafter recited, insofar as such terms are necessary for performance. The term "consisting of … …" does not include any components, steps or processes not specifically described or listed. Unless explicitly stated otherwise, the term "or" refers to the listed individual members or any combination thereof.

In order to make the technical problems, technical solutions and advantageous effects solved by the present invention more apparent, the present invention is further described in detail below with reference to the following embodiments.

Examples

The following examples are used herein to demonstrate preferred embodiments of the invention. It will be appreciated by those of skill in the art that the techniques disclosed in the examples which follow represent techniques discovered by the inventor to function in the invention, and thus can be considered to constitute preferred modes for its practice. Those of skill in the art should, in light of the present disclosure, appreciate that many changes can be made in the specific embodiments which are disclosed and still obtain a like or similar result without departing from the spirit or scope of the invention.

Unless defined otherwise, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art to which this invention belongs and the disclosures and materials cited therein are hereby incorporated by reference.

Those skilled in the art will recognize, or be able to ascertain using no more than routine experimentation, many equivalents to the specific embodiments of the invention described herein. Such equivalents are intended to be encompassed by the following claims.

s1, preparation of mixed standard working solution:

weighing 10mg of clopidogrel standard substance, and diluting the standard substance to 10mL by using methanol to obtain 1mg/mL clopidogrel single-standard mother solution; then taking 50 mu L of clopidogrel single-standard mother liquor and diluting the mother liquor to 1mL by using methanol to obtain 49.7250 mu g/mL clopidogrel single-standard stock solution; the preparation process of other single-standard mother liquor is the same as above, and 10 single-standard stock solutions corresponding to the cardiovascular drugs are respectively obtained, and are shown in table 1.

TABLE 1

(2) Preparation of stock solution (M0)

The preparation method is shown in table 2, and the prepared product is sealed and stored in a refrigerator at the temperature of 80 ℃ below zero for later use.

TABLE 2 formulation of the stock solutions mixed with standards (M0)

(3) Preparation of mixed standard working solution

The blank matrix is human serum filtered

Diluting 200. mu.L of M0 with 3800. mu.L of a blank medium to obtain W1, diluting 400. mu.L of W1 with 100. mu.L of a blank medium to obtain W2, diluting 300. mu.L of W1 with 200. mu.L of a blank medium to obtain W3, diluting 300. mu.L of W1 with 300. mu.L of a blank medium to obtain W4, diluting 200. mu.L of W1 with 300. mu.L of a blank medium to obtain W5, diluting 100. mu.L of W1 with 400. mu.L of a blank medium to obtain W6, diluting 100. mu.L of W1 with 900. mu.L of a blank medium to obtain W7, diluting 300. mu.L of W7 with 300. mu.L of a blank medium to obtain W8, diluting 100. mu.L of W7 with 400. mu.L of a blank medium to obtain W9, diluting 50. mu.L of W7 with 450. mu.L of a blank medium to obtain W10, and hermetically storing the mixture at-80 ℃ in a refrigerator; the concentrations of the respective mixed standard working liquids are shown in Table 3.

TABLE 3 concentration of mixed standard working fluid

S2, preparation of quality control products:

respectively taking 50 μ L, 150 μ L and 400 μ L of the standard solution W1, diluting to 500 μ L with blank matrix, mixing,

respectively obtaining three quality control products of low, medium and high.

S3, processing the sample to be detected:

(1) precisely removing the biological sample and 200. mu.L of blank matrix into a clean and numbered 1.5mL centrifuge tube (using an orange 96-well centrifuge tube holder);

(2) adding 1mL of methanol solution, and performing vortex oscillation for 5min under the condition of 2000rpm by using an MTV-100 multi-tube vortex mixer;

(3) centrifuging for 5min at 8 deg.C and rotation speed of 13000rpm by using Sigma centrifuge (24/48 wells);

(4) transfer 150 μ L of supernatant to a 96-well dipstick using a pipette (note pipette tip submerge into solution depth, prevent aspiration pellet) and freeze at-20 ℃ for mass spectrometric injection.

And (3) processing quality control products: treating the sample solution;

treatment of standard solutions: the same as the treatment of the sample solution.

Data processing:

in the experiment, an MRM mode is adopted to monitor ion pairs (Q1/Q3) of 10 drugs, CE and the like of different ion pairs are selected for optimization, the optimal result corresponding to the highest signal intensity of the ions can be seen from an optimized chromatogram, and other parameters can be selected to be proper values according to a reference value range provided by an instrument so as to ensure stronger signal intensity. Obtaining an ion chromatogram of the standard: and drawing an external standard curve:

an external standard quantitative method is adopted, the concentration of a standard substance is taken as an X axis, the peak area of a standard substance solution is taken as a Y axis, an external standard curve is established, the linear fitting equations of the 10 medicines in respective concentration ranges are good in linearity, the correlation coefficients are basically more than 0.99, the curve spectrogram is shown in figures 11 to 20, and the specific parameters are shown in a table 4:

table 4: linear regression equation and linear correlation coefficient for 10 drugs:

s4, respectively detecting the samples 1-7 to be detected: the results are shown in Table 5

The detection conditions were as follows:

the chromatographic conditions were as follows:

gradient elution mode is adopted.

Wherein the elution gradient is as follows: in 0-0.3min, the volume of the mobile phase B liquid is 2%; in 0.3-2.0min, the volume of the mobile phase B liquid is increased to 98%; the volume of the mobile phase B liquid is maintained to be 98 percent within 2.0-3.5 min; reducing the volume of the mobile phase B liquid to 2% in 3.6min, and maintaining the volume at 2% to 4.0 min;

tandem-mass spectrometry conditions were as follows:

TABLE 5, actual test results

Are all in the linear range.

Accuracy verification

Accuracy experiment: inter-group accuracy, obtained by analyzing two samples of different concentration for at least three days (6 replicates per concentration point), see table 6; qualified standards require that the concentration of each level measured on average be within 15% of theoretical, i.e., the accuracy range is between 85% and 115%. Quality control: low-concentration quality control of LQC; controlling the concentration in MQC; HQC high concentration quality control

Table 6: three-day accuracy data of quality control sample detection

Precision verification

Precision: QC was measured at three different concentrations at once, with the number of samples per concentration required to be no less than 5 (n-6), and the qualifying standards required a CV of QC samples at each level of concentration of 15% or less, as shown in table 7:

table 7: results of precision verification

Note: LQC is a low-concentration quality control product; MQC is a medium concentration quality control product; HQC is a high-concentration quality control product.

The invention adopts an LC-MS method to simultaneously detect 10 anti-cardiovascular drugs. The invention adopts an external standard method for quantitative measurement, namely, expensive internal standard substances are not needed to reduce the detection cost. The 10 medicines can be simultaneously detected in a short time (4min) with high flux and high sensitivity, and the method has high precision and repeatability in view of examining the precision and repeatability of the result and comparing the precision and accuracy data. In a word, the method has the advantages of high sensitivity, strong specificity, accuracy and simple pretreatment steps, can simultaneously complete the separation and detection of 10 medicines within 4min, adopts an external standard method to simply realize the quantification of the organic acid, has high repeatability and low cost, and meets the basic requirements on precision and repeatability.

All documents referred to herein are incorporated by reference into this application as if each were individually incorporated by reference. Furthermore, it should be understood that various changes and modifications of the present invention can be made by those skilled in the art after reading the above teachings of the present invention, and these equivalents also fall within the scope of the present invention as defined by the appended claims.

Claims

1. A detection kit for 10 kinds of cardiovascular drug serum based on LC-MS is characterized by comprising a mixed standard stock solution; the solutes of the 10 single-standard stock solutions are clopidogrel, rivaroxaban, apixaban, dabigatran, ticagrelor, rosuvastatin, deshydroxyethoxy ticagrelor, atorvastatin, o-hydroxy atorvastatin and p-hydroxy atorvastatin, respectively.

2. The LC-MS-based detection kit for 10 cardiovascular drug serums, which is characterized by further comprising a blank matrix; the blank matrix is human serum.

3. The LC-MS-based detection kit for 10 cardiovascular drug serums according to claim 1, further comprising a precipitating agent; the precipitant is methanol.

4. The LC-MS-based detection kit for 10 cardiovascular drug serums, which is characterized by further comprising a mobile phase; the mobile phase comprises mobile phase A liquid and mobile phase B liquid;

the mobile phase A liquid is 1mM-5mM ammonium formate aqueous solution containing 0.1% formic acid; the mobile phase B liquid is 1mM-5mM ammonium formate methanol solution containing 0.1% formic acid.

5. The LC-MS-based detection kit for 10 cardiovascular drug serums, which is characterized by further comprising a quality control product; the quality control products comprise high quality control products, medium quality control products and low quality control products.

6. The detection method of the detection kit for 10 kinds of cardiovascular drug serum based on LC-MS is characterized by comprising the following steps:

s1, preparation of mixed standard working solution: preparing 10 single-standard stock solutions with different concentrations by using methanol respectively, and then preparing mixed standard stock solutions with different concentrations by taking the single-standard stock solutions with different volumes respectively; diluting the mixed standard stock solution with a blank matrix step by step to respectively obtain mixed standard working solutions W1-W9;

s2, preparation of quality control products: diluting the mixed standard working solution W1 with a blank matrix to respectively obtain three quality control products of low, medium and high;

s3, processing the sample to be detected: precisely transferring a biological sample and a blank matrix into a centrifugal tube, adding a methanol solution, carrying out vortex oscillation and centrifugation, and then freezing at-20 ℃;

and S4, detecting the sample to be detected.

7. The detection method of the LC-MS-based 10 cardiovascular drug serum detection kit according to claim 6, further comprising the steps of detecting the mixed standard working solution and quality control substance, and drawing a standard curve: and taking the peak area of the target object of the mixed standard working solution as the ordinate y of the standard curve graph, and taking the concentration in the mixed standard working solution as the abscissa x of the standard curve graph to obtain a standard curve equation.

8. The detection method of the LC-MS-based 10 cardiovascular drug serum detection kit according to claim 6, wherein the detection conditions of the sample to be detected are as follows:

the chromatographic conditions were as follows:

adopting a gradient elution mode; wherein the elution gradient is as follows: in 0-0.3min, the volume of the mobile phase B liquid is 2%; in 0.3-2.0min, the volume of the mobile phase B liquid is increased to 98%; the volume of the mobile phase B liquid is maintained to be 98 percent within 2.0-3.5 min; reducing the volume of the mobile phase B liquid to 2% in 3.6min, and maintaining the volume at 2% to 4.0 min;

tandem-mass spectrometry conditions were as follows:

an ion source: electrospray ion source, positive ion mode; spray capillary voltage: 1.0-3.5 KV; desolvation gas temperature: 400-500 ℃; desolventizing air flow rate: 800-1000L/Hr; ion source temperature: 130 ℃ and 150 ℃; desolventizing gas pressure: 8 bar; collision gas pressure: 0.7 bar; scanning mode: and (5) monitoring multiple reactions.

9. The method for detecting 10 kinds of cardiovascular drug serum based on LC-MS in claim 8, wherein the quantitative analysis ion pairs for multi-reaction monitoring are as follows: clopidogrel quantitation ion pair m/z 322.0 → 211.9, rivaroxaban quantitation ion pair m/z 435.0 → 144.8, apixaban quantitation ion pair m/z 460.1 → 443.2, dabigatran quantitation ion pair m/z 472.2 → 289.1, ticagrelor quantitation ion pair m/z523.1 → 152.9, rosuvastatin quantitation ion pair m/z 481.5 → 258.1, deshydroxyethoxy ticagrelor quantitation ion pair m/z 479.1 → 152.9, atorvastatin quantitation ion pair m/z 559.5 → 440.1, orthohydroxy atorvastatin quantitation ion pair m/z 574.9 → 440.1, hydroxyalipivastatin quantitation ion pair m/z 574.7 → 440.2.