Pretreatment method for liquid chromatography-tandem mass spectrometry of pesticide and veterinary drug residues in serum

Abstract

The invention belongs to the technical field of liquid chromatography-mass spectrometry detection pretreatment, and particularly relates to a pretreatment method for liquid chromatography-tandem mass spectrometry analysis of pesticide and veterinary drug residues in serum, which comprises the following steps: (S1) carrying out heating reaction on Sc (III) salt, Cu (II) salt and 1H-pyrazole-4-formic acid (H2PyC) in a polar aprotic solvent, and cooling to obtain a green crystal, namely MOF-919; the chemical formula of the MOF-919 is [Sc < 3 > (mu3-O) (OH) < 3 >] [Cu3 (mu3-O) (mu-PyC) < 3 > (H2O) < 6 >] < 2 >; (S2) mixing the serum sample with an acetonitrile solution containing formic acid, carrying out ultrasonic treatment, vortex oscillation and centrifugation, taking supernate, and diluting the supernate with an aqueous solution containing formic acid to obtain a to-be-purified solution; and (S3) adding MOF-919 into the to-be-purified liquid, mixing, performing ultrasonic treatment, performing vortex oscillation, centrifuging, and taking supernate, thereby completing the pretreatment of the to-be-purified liquid. According to the method, the MOF-919 is used for adsorbing chemical pollutant residues in serum, especially phospholipids, so that the purpose of removing the chemical pollutant residues in blood is achieved. The method is simple and convenient to operate, small in organic solvent consumption and good in purification effect, and can be widely applied to residue analysis of chemical pollutants in serum.

Description

TECHNICAL FIELD

[0001] The application belongs to the field of liquid chromatography-mass spectrometry detection pretreatment technology, and particularly relates to a pretreatment method for liquid chromatography-tandem mass spectrometry analysis of residues of agricultural and veterinary drugs in serum. BACKGROUND

[0002] In environmental health research, the detection of blood pollutants is of great significance for assessing individual exposure levels, identifying potential health risks, and tracing pollution sources. Early detection of pollutant accumulation in the body can provide scientific basis for disease prevention and intervention. In addition, the detection results can provide key support for pollution control, environmental protection policy making, and related legal accountability, thus playing an important role in protecting public health and improving environmental quality. In recent years, the rapid development of high-resolution mass spectrometry technology has provided a powerful tool for non-targeted analysis, which can simultaneously detect thousands of compounds in biological samples. However, due to the fact that the concentration of exogenous chemicals (such as pesticides and plasticizers) in the blood of ordinary people is usually hundreds to thousands of times lower than that of endogenous compounds, the ion suppression effect caused by high-abundance endogenous chemicals often leads to the failure to effectively detect trace and ultra-trace exogenous chemicals.

[0003] In the sample pretreatment stage, removing the interference of endogenous compounds in blood samples is a key way to solve this problem. In the non-targeted monitoring of plasma or serum samples, although traditional sample preparation methods (such as ice methanol or acetonitrile protein precipitation) can extract a large number of compounds, due to the interference of endogenous compounds (such as phospholipids), there are problems such as large amount of organic solvent, long operation time and unsatisfactory purification effect.

[0004] Therefore, this research proposes a serum sample pretreatment method based on scandium-based bimetallic organic framework. This method can effectively remove phospholipids in serum, significantly reduce ion suppression effect, and improve the detection sensitivity of exogenous chemicals, thus providing new technical support for sample pretreatment of chemical pollutant detection.

[0005] CN114755355A reports a phospholipid removal agent and its application in removing phospholipids from biological samples. The phospholipid removal agent is composed of component A and component B. Component A is a dextran salt, and component B is a zirconium source. The molar ratio of component A to component B is 0.1-1.7:2.5-5. The dextran salt is dextran sulfate, and the zirconium source is zirconium oxychloride. The phospholipid at least contains lysophosphatidylcholine. However, this polyanion-metal ion system is difficult to efficiently remove phospholipids while maintaining good recovery of certain analytes.

[0006] A zirconium dioxide coated silica core-shell filler was reported by Shanghai Jiao Tong University to selectively adsorb phospholipids, and the larger specific surface area and selective adsorption of phospholipids were used to pretreat serum samples with ZrO2 / SiO2 SPE small columns. However, this article only explores the adsorption efficiency of zirconium dioxide coated silica core-shell filler for phospholipids, and does not explore the recovery effect of other substances.

[0007] The inventor's previous patent CN202510814916.9 describes a pretreatment method for serum liquid chromatography-tandem mass spectrometry analysis, which uses a complex formed by 2,4,6-tris(4-carboxyphenyl)-1,3,5-triazine and Zr in a molar ratio of 1:3 as a phospholipid adsorbent for sample pretreatment. The phospholipid removal rate is high, the analyte recovery rate is excellent, and it can be widely used for residual analysis of chemical contaminants in serum, but the recovery rate of some detected substances is low. SUMMARY

[0008] To solve the problems of insufficient phospholipid removal efficiency in blood samples, low recovery rate of certain analytes, and complex operation in the prior art, the present application provides a method for adsorbing chemical contaminant residues in serum, especially phospholipids, using MOFs, to achieve the purpose of removing chemical contaminant residues in blood. The method is simple to operate, uses less organic solvent, has good purification effect, and can be widely used for residual analysis of chemical contaminants in serum. Specifically, the present application provides the following technical solutions to solve the above problems: A pretreatment method for liquid chromatography-tandem mass spectrometry analysis of agricultural and veterinary drug residues in serum, comprising the following steps: (S1) Sc(III) salt, Cu(II) salt and 1H-pyrazole-4-carboxylic acid (H2PyC) are heated in a polar aprotic solvent to obtain a green crystal, which is MOF-919, and the chemical formula of MOF-919 is [Sc3(μ3-O)(OH)3][Cu3(μ3-O)(μ-PyC)3(H2O)6]2; (S2) Mix the serum sample with a formic acid-containing acetonitrile solution, ultrasonic, vortex oscillation, centrifugation, take the supernatant, dilute with a formic acid-containing water solution, and obtain the purified liquid; (S3) Add MOF-919 to the purified liquid, mix, ultrasonic, vortex oscillation, centrifugation, take the supernatant, and complete the pretreatment of the purified liquid.

[0009] Further, in step (S1), the Sc(III) salt is at least one of ScCl3 and its hydrate (ScCl3·6H2O), the Cu(II) salt is at least one of Cu(NO3)2, CuCl2 and its hydrate, and the polar aprotic solvent is at least one of N,N-dimethylformamide (DMF) and dimethyl sulfoxide (DMSO).

[0010] Further, in step (S1), the Sc(III) salt, Cu(II) salt, 1H-pyrazole-4-carboxylic acid are in a molar ratio of Sc:Cu:H2PyC of 1-1.2:2-2.5:2-3.

[0011] Further, in step (S1), after obtaining green crystals, a solvent exchange step is further included: the green crystals are immersed in a polar aprotic solvent for 1-3 days, and then immersed in an alcohol solvent for 1-3 days, the polar aprotic solvent is defined as before, and is selected from at least one of DMF and DMSO, and the alcohol solvent is selected from at least one of methanol, ethanol, and isopropanol. The heating reaction is heated to 80-120℃ for 10-20h, such as 100℃ for 15h.

[0012] Further, in step (S2), the acetonitrile containing formic acid, and the formic acid concentration in the aqueous solution containing formic acid is independently 0.1-0.2wt%. The volume ratio of the serum sample and the formic acid acetonitrile solution is 1:3-5, such as 1:4.

[0013] Further, in steps (S2) and (S3), the ultrasonic frequency is 60-120kHz; the vortex oscillation time is 30-60s; the ultrasonic time is 5-30min; the centrifugal speed is 8000-15000rpm, the centrifugal temperature is 0-10℃, and the centrifugal time is 5-20min; and the supernatant is diluted 1:1 with an aqueous solution (0.1% formic acid).

[0014] Further, in step (S3), the dosage ratio of the purified liquid to MOF-919 is 1mL:10-50mg, preferably 1mL:10-20mg.

[0015] The inventors found that the prepared MOF-919 has specific adsorption for phospholipids, does not adsorb the detected substances such as agricultural and veterinary drugs, reduces the interference of phospholipids on the detected substances, and has a high recovery rate of the detected substances.

[0016] Further, after step (S3), there is step (S4): the supernatant is separated and determined by UPLC-MS / MS to obtain the removal efficiency of phospholipids. Further, after step (S4), there is step (S5): the supernatant is separated and determined by UPLC-MS / MS, and quantified by an external standard method to obtain the content of chemical pollutants.

[0017] Furthermore, in step (S4), the phospholipids are 2 types of lysophosphatidylethanolamine (LPE): LPE 16:0, LPE18:0; 4 types of lysophosphatidylcholine (LPC): LPC 15:0, LPC 16:0, LPC 18:0, LPC 22:4; 4 types of phosphatidylcholine (PC): PC p- 16:0 / 18:0, PC p -16:0 / 20:1, PC p -18:0 / 14:0, PC p- 18:0 / 18:0; and 4 sphingomyelins (SM): SM d18:1 / 12:0, SM d18:1 / 14:0, SM d18:1 / 14:1, SM d18:1 / 16:0; Furthermore, in step (S4), the chromatographic column used in the ultra-high performance liquid chromatography method is ACQUITY CSH C18 (2.1 mm×100 mm, 1.7 μm). Mobile phase: 10-20 mM ammonium formate + 0.1-0.2 wt% formic acid in acetonitrile / water (6:4 to 4:6, v / v) (A) and 10-20 mM ammonium formate + 0.1-0.2% formic acid in isopropanol / acetonitrile (9:1 to 2:1, v / v) (B); gradient elution program: 40%-43% B (0-2.0 min), 43%-50% B (2.0-2.1 min), 50%-54% B (2.1-12.0 min), 54%-70% B (12.0-12.1 min), 70%-99% B (12.1-18.0 min), 99%-40% B (18.0-18.1 min), 40% B (18.1-20.0 min); flow rate: 0.35-0.40 mL / min; column temperature 40-45°C; injection volume 5-10 μL. In gradient elution programs, the mobile phase and time are expressed as is well known in the art. For example, 40%-43% B (0-2.0 min) means that from 0 to 2.0 minutes, the mobile phase gradually changes from 40% mobile phase B (the remainder is mobile phase A) to 43% mobile phase B (the remainder is mobile phase A). Another example is 99%-40% B (18.0-18.1 min) means that from 18.0 to 18.1 minutes, the mobile phase gradually changes from 99% mobile phase B (the remainder is mobile phase A) to 40% mobile phase B (the remainder is mobile phase A). Percentages are expressed by volume.

[0018] Furthermore, in step (S5), the chemical pollutants are selected from pesticides or veterinary drugs. For pesticides, the chromatographic column used in the ultra-high performance liquid chromatography method is ACQUITY UPLC HSS T3 (2.1 mm × 100 mm, 1.8 μm); for veterinary drugs, the chromatographic column used in the ultra-high performance liquid chromatography method is ACQUITY UPLC BEH C18 (2.1 mm × 100 mm, 1.7 μm).

[0019] Furthermore, in step (S5), for pesticides, the mobile phases used in the ultra-high performance liquid chromatography method are: 2-5 mM ammonium formate + 0.01-0.05% (v / v) formic acid in water (A) and 2-5 mM ammonium formate + 0.01-0.05% (v / v) formic acid in methanol (B); the gradient elution program is 3% B (0-1.0 min), 3%-15% B (1.0-1.5 min), 15%-50% B (1.5-2.5 min), 50%-70% B (2.5-18.0 min), 70%-98% B (18.0-23.0 min), 98% B (23.0-27.0 min), 98%-3% B (27.0-27.1 min), 3% B (27.1-30.0 min); the flow rate is 0.3-0.5 mL / min; the column temperature is 40-45°C, and the injection volume is 2-5 μL; for veterinary drugs, the mobile phases used in the ultra-high performance liquid chromatography method are: 0.5-1.0 mM ammonium fluoride + 0.1-0.2% (v / v) formic acid in water (A) and acetonitrile / methanol (v / v = 1 / 1 to 1 / 1.5) (B); the flow rate is 0.3-0.5 mL / min. The gradient elution program was 3-10% B (0-2.0 min), 10%-15% B (2.0-5.0 min), 10-15% B (5.0-10.0 min), 15%-30% B (10.0-15.0 min), 30%-50% B (15.0-20.0 min), 50%-100% B (20.0-24.0 min), 100% B (24.0-28.0 min), 100%-3% B (28.0-28.5 min), 3-5% B (28.5-29.0 min); the flow rate was 0.3-0.5 mL / min; the column temperature was 40-45°C, and the injection volume was 3-5 μL.

[0020] The present invention also provides the use of a metal organic framework MOF-919 in removing phospholipids from a blood sample, wherein the chemical formula of the MOF-919 is [Sc3(μ3-O)(OH)3][Cu3(μ3-O)(μ-PyC)3(H2O)6]2.

[0021] MOF-919 is a known MOFs material, see the document "Mesoporous Cages in Chemically Robust MOFs Created by a Large Number of Vertices with Reduced Connectivity". The present invention is the first time to use this MOFs for adsorbent of phospholipid in serum sample, and found that it can specifically adsorb and remove phospholipid without interference with other components to be detected. And this specific and efficient adsorption of phospholipid characteristics has not been observed in other MOFs.

[0022] Further, the organic metal framework MOF-919 is obtained by a preparation method comprising the following steps: dissolving Sc(III) salt and / or its hydrate, Cu(II) salt and / or its hydrate, and ligand 1H-pyrazole-4-carboxylic acid (H2PyC) in a polar aprotic solvent, heating the mixture, cooling, and the obtained green crystals are subjected to solvent exchange with polar aprotic solvent and alcohol solvent in turn, and drying.

[0023] Further, the Sc(III) salt is selected from ScCl3 and its hydrate; the Cu(II) salt is selected from at least one of CuCl2 and Cu(NO3)2, and the polar aprotic solvent is selected from at least one of N,N-dimethylformamide and N,N-dimethylformamide. The heating temperature is 80-120°C, and the heating time is 10-20h.

[0024] Further, the amounts of Sc(III) salt, Cu(II) salt and 1H-pyrazole-4-carboxylic acid satisfy the molar ratio of Sc:Cu:1H-pyrazole-4-carboxylic acid of 1-1.2:2-2.5:2-3, preferably 1:2:2; and the amounts of Sc(III) salt and organic solvent are 5-10mg:1mL.

[0025] The inventors unexpectedly found that among a large number of organic metal frameworks, PCN-919 exhibits excellent effect of adsorbing and removing phospholipid in serum. The possible reason is that MOF-919 has a large specific surface area, and the pore size is large enough to allow the entry of phospholipid molecules, in addition, Sc 3+ in MOF-919 can bind with the phosphate group in phospholipid through electrostatic interaction. BRIEF DESCRIPTION OF DRAWINGS

[0026] Figure 1 is a SEM image of MOF-919 obtained in the preparation example; Figure 2 is a N2 adsorption-desorption curve and pore size distribution graph of MOF-919 obtained in the preparation example; Figure 3are liquid chromatograms of SM d18:1 / 16:0 before and after adsorption by MOF-919; Figure 4 are adsorption performance of MOF-919 on 14 kinds of phospholipids. DETAILED DESCRIPTION

[0027] The experimental methods described in the following examples are all conventional methods unless otherwise specified; the reagents and materials described are all commercially available unless otherwise specified.

[0028] Preparation Example 76.2 mg of ScCl3·6H2O, 135.6 mg of Cu(NO3)2·3H2O, and 34.8 mg of 1H-pyrazole-4-carboxylic acid (H2PyC) were placed in a PTFE bottle, and 10 mL of N,N-dimethylformamide (DMF) was added and ultrasonically dissolved. The mixture was heated to 100°C under reflux for 15 h, and green crystals were obtained after cooling to room temperature. The green crystals were immersed in DMF for solvent exchange for 2 days, and then solvent exchange was performed with ethanol for 2 days, filtration, and vacuum drying to obtain MOF-919.

[0029] Figure 1 is a SEM image of PCN-919 obtained in the preparation example. It can be seen that the prepared PCN-919 has an octahedral structure, and the size is about 10 μm.

[0030] Figure 2 is the N2adsorption-desorption curve and pore size distribution diagram of PCN-919 obtained in the preparation example. The Brunauer-Emmett-Teller specific surface area of MOF-919 is 1680.29 m 2 ·g -1 , with pore channels of 3.7 nm, 4.5 nm, and 6.0 nm.

[0031] Example 1 The representative phospholipids selected are: 2 kinds of lysophosphatidylethanolamine (LPE): LPE 16:0, LPE 18:0; 4 kinds of lysophosphatidylcholine (LPC): LPC 15:0, LPC 16:0, LPC 18:0, LPC 22:4; 4 kinds of phosphatidylcholine (PC): PC p-16:0 / 18:0, PC p-16:0 / 20:1, PC p-18:0 / 14:0, PC p-18:0 / 18:0; and 4 kinds of sphingomyelin (SM): SM d18:1 / 12:0, SM d18:1 / 14:0, SM d18:1 / 14:1, SM d18:1 / 16:0, which basically covers various types of phospholipids.

[0032] Chromatographic separation of phospholipid analytes was performed using an ACQUITY CSH C18 (2.1 mm x 100 mm, 1.7 μm) column. Mobile phase: 10 mM ammonium formate + 0.1% formic acid in acetonitrile / water (6:4, v / v) (A) and 10 mM ammonium formate + 0.1% formic acid in isopropanol / acetonitrile (9:1, v / v) (B); gradient elution program was 40%-43% B (0-2.0 min), 43%-50% B (2.0-2.1 min), 50%-54% B (2.1-12.0 min), 54%-70% B (12.0-12.1 min), 70%-99% B (12.1-18.0 min), 99%-40% B (18.0-18.1 min), 40% B (18.1-20.0 min); flow rate was 0.35 mL / min; column temperature was 45 °C, injection volume was 5 μL, and total cycle time for each sample was 30 min.

[0033] Mass spectrometry analysis was performed using a Waters Xevo TQ-S triple quadrupole mass spectrometer and operated in multiple reaction monitoring (MRM) mode. The main parameters were as follows: ion source: electrospray ion source (ESI); ionization mode: positive ion mode; ion source temperature: 350 °C; retention time (RT), quantitative ions, qualfication ions, collision energy, declustering potential, and other parameters are shown in Table 1.

[0034] Table 1 Mass spectrometry parameters of 14 kinds of phospholipids .

[0035] Method 1: Take 500 μL of serum, add 5 mg of MOF-919 powder, vortex for 5 min, then centrifuge at 10000 rpm for 5 min, mix 100 μL of supernatant with 400 μL of acetonitrile solution containing 0.1% formic acid, ultrasonic for 15 min, centrifuge at 4 °C 12000 rpm for 10 min, take 250 μL of supernatant, dilute with equal amount of water containing 0.1% formic acid, take 200 μL for detection, and the result shows that there is no removal effect on phospholipids, indicating that adding the material before acetonitrile protein precipitation cannot remove phospholipids.

[0036] Method 2: 100 μL serum and 400 μL acetonitrile solution containing 0.1% formic acid were mixed by ultrasonic for 15 min, then centrifuged at 12000 rpm for 10 min at 4°C, 250 μL supernatant was taken, diluted with equal volume of water containing 0.1wt% formic acid, 5 mg MOF-919 powder was added into 500 μL diluent, vortexed for 5 min, centrifuged at 10000 rpm for 5 min, and 200 μL supernatant was taken for detection. Figure 3 is the adsorption performance of MOF-919 to 14 kinds of phospholipids. After acetonitrile precipitation of protein, MOF-919 showed excellent adsorption performance to 14 kinds of phospholipids. It is indicated that acetonitrile needs to be used for protein precipitation before using MOF-919 to adsorb phospholipids. The adsorption rate calculation formula is as follows: ; The peak area is the peak area of the characteristic peak of the liquid chromatogram, and the retention time of each phospholipid is different, which is shown in Table 1. The results show that after protein precipitation, the adsorption rate of MOF-919 to phospholipids is as follows: the adsorption rate of 2 kinds of LPE is more than 90%, the adsorption rate of 4 kinds of LPC is 80%-95%, the adsorption efficiency of 3 kinds of PC is more than 95%, and the adsorption rate of 4 kinds of SM is more than 95%. The above results show that PCN-919 has excellent phospholipid adsorption performance on serum after acetonitrile precipitation of protein.

[0037] Figure 3 is the liquid chromatogram of MOF-919 before and after adsorption of phospholipid SM d18:1 / 16:0. Figure 4 is the adsorption performance of MOF-919 to 14 kinds of phospholipids, wherein Q is the adsorption rate obtained by method 1, and H is the recovery rate obtained by method 2. The inventors also tried other kinds of MOFs, such as ZIF-8, UIO-66, and found that their adsorption performance to 14 kinds of phospholipids was far inferior to MOF-919, and the adsorption rate to phospholipids was only 40-60%.

[0038] Example 2 In the spiked recovery experiment, 1 mL serum was taken into a 15 mL polypropylene centrifuge tube, then 4 mL acetonitrile solution containing 0.1% formic acid was added and vortexed for 30 s, then ultrasonic was performed for 15 min, centrifuged at 12000 rpm for 10 min at 4°C, 4 mL supernatant was taken, diluted with equal volume of water containing 0.1% formic acid, and 50 μg kg -1 The concentration level of the chemical hazard was spiked. 5 mg MOF-919 was dispersed in 500 μL supernatant, vortexed for 5 min, and PCN-777 was separated by centrifugation at 10000 r / min for 5 min. 200 μL supernatant was taken, and the concentration of chemical hazard factor was analyzed by HPLC-MS / MS.

[0039] For pesticide standards, liquid chromatography analysis was performed using a Waters Acquity Ultra Performance LC. The analytes were chromatographically separated using an ACQUITY UPLC HSS T3 (2.1 mm x 100 mm, 1.8 pm) column. The column temperature was 40 °C and the injection volume was 2 pL. The mobile phase was 2 mM ammonium formate + 0.01% (v / v) formic acid in water (A) and 2 mM ammonium formate + 0.01 w% formic acid in methanol (B); the flow rate was 0.3 mL / min. The gradient elution program was 3% B (0-1.0 min), 3%-15% B (1.0-1.5 min), 15%-50% B (1.5-2.5 min), 50%-70% B (2.5-18.0 min), 70%-98% B (18.0-23.0 min), 98% B (23.0-27.0 min), 98%-3% B (27.0-27.1 min), 3% B (27.1-30.0 min). The total cycle time for each sample was 30.0 min.

[0040] Mass spectrometry analysis was performed using a Waters Xevo TQ-S triple quadrupole mass spectrometer and operated in multiple reaction monitoring (MRM) mode. The main parameters were as follows, ion source: electrospray ion source (ESI); ionization mode: positive ion mode; ion source temperature: 350 °C.

[0041] For veterinary drug standards, liquid chromatography analysis was performed using a Waters Acquity Ultra Performance LC high-performance liquid chromatograph. The analytes were chromatographically separated using an ACQUITY UPLC BEH C18 (2.1 mm x 100 mm, 1.7 μm) column. The column temperature was 40℃, and the injection volume was 3 μL. The mobile phase was 0.5 mM ammonium fluoride + 0.1wt% formic acid aqueous solution (A) and acetonitrile / methanol (v / v = 1 / 1) (B); the flow rate was 0.3 mL / min. The gradient elution program was 3% B (0-2.0 min), 3%-15% B (2.0-5.0 min), 15% B (5.0-10.0 min), 15%-30% B (10.0-15.0 min), 30%-50% B (15.0-20.0 min), 50%-100% B (20.0-24.0 min), 100% B (24.0-28.0 min), 100%-3% B (28.0-28.5 min), 3% B (28.5-29.0 min). The total cycle time for each sample was 29.0 min.

[0042] Mass spectrometry analysis was performed using a Waters Xevo TQ-XS triple quadrupole mass spectrometer and operated in multiple reaction monitoring (MRM) mode. The main parameters were as follows: ion source: electrospray ion source (ESI); ionization mode: positive ion mode; ion source temperature: 400℃.

[0043] A total of 556 pesticides and veterinary drugs were tested, and the results are shown in Table 2 below.

[0044] To evaluate the full recovery performance of the material, the accuracy and precision of the method were evaluated by recovery experiments at an addition level of 50 ppb (n = 3). The recovery rate and the relative standard deviation (RSD) represent the accuracy and precision of the method, respectively. As can be seen from Table 2, for serum samples, MOF-919 achieved good recovery rate R and low RSD for 556 chemical hazards (pesticides and veterinary drugs) at a concentration level of 50 ppb. Although the recovery rate of some pesticides and veterinary drugs was low, all compounds could be detected, meeting the qualitative requirements of non-targeted screening. In addition, among the 556 chemical hazards, the matrix effect factor (ME) of most of the chemical hazards was between 0.8 and 1.2. If the serum is not treated with MOF-919, a more serious matrix effect will occur, which will result in the inability to detect trace chemical hazards.

[0045] Table 2 Information of 566 pesticides and veterinary drugs and recovery rate (50 μg kg -1 )

Claims

1. A pretreatment method for liquid chromatography-tandem mass spectrometry analysis of pesticide residues in serum, characterized in that: The following steps are involved: (S1) Sc(III) salt, Cu(II) salt and 1H-pyrazole-4-carboxylic acid (H2PyC) are heated to react in a polar aprotic solvent, and after cooling, green crystals are obtained, namely MOF-919; the chemical formula of MOF-919 is [Sc3(μ3-O)(OH)3][Cu3(μ3-O)(μ-PyC)3(H2O)6]2; (S2) mixing the serum sample with an acetonitrile solution containing formic acid, sonicating, vortexing, and centrifuging, and diluting the supernatant with an aqueous solution containing formic acid to obtain a solution to be purified; (S3) MOF-919 is added to the liquid to be purified, mixed, sonicated, vortexed, centrifuged, and the supernatant is collected to complete the pretreatment of the liquid to be purified.

2. The method according to claim 1, characterized in that In step (S1), the Sc(III) salt is at least one of ScCl3 and its hydrates; the Cu(II) salt is at least one of Cu(NO3)2, CuCl2 and its hydrates; the polar aprotic solvent is at least one selected from N,N-dimethylformamide and dimethyl sulfoxide; and / or The heating reaction is heated to 80-120°C for 10-20 hours.

3. The method according to claim 1, characterized in that In step (S1), the molar ratio of Sc(III) salt, Cu(II) salt and 1H-pyrazole-4-carboxylic acid is 1-1.2:2-2.5:2-3.

4. The method according to claim 1, wherein In step (S1), after obtaining the green crystals, the step of solvent exchange is further included: immersing the green crystals in a polar aprotic solvent for solvent exchange for 1-3 days, and then immersing them in an alcohol solvent for solvent exchange for 1-3 days; the alcohol solvent is selected from at least one of methanol, ethanol, and isopropanol.

5. The method according to claim 1, wherein In step (S2), the formic acid concentration in the acetonitrile containing formic acid and the aqueous solution containing formic acid is independently 0.1-0.2 wt %; and the volume ratio of the serum sample to the formic acid acetonitrile solution is 1:3-5.

6. The method according to claim 1, characterized in that In step (S2) and step (S3), the ultrasonic frequency is 60-120 kHz; the vortex oscillation time is 30-60 s; the ultrasonic time is 5-30 min; the centrifugal speed is 8000-15000 rpm, the centrifugal temperature is 0-10°C, and the centrifugation time is 5-20 min. The supernatant is diluted with an aqueous solution containing 0.1-0.5 wt% formic acid.

7. The method according to claim 1, characterized in that In step (S3), the ratio of the liquid to be purified to MOF-919 is 1 mL: 10-50 mg.

8. The method according to claim 1, characterized in that After step (S3), there is a step (S4): the supernatant is separated and measured by UPLC-MS / MS to obtain the removal efficiency of phospholipids.

9. The method according to claim 8, characterized in that After step (S4), there is a step (S5): the supernatant is separated and measured by UPLC-MS / MS, and quantified by an external standard method to obtain the content of chemical pollutants.

10. Use of a metal-organic framework (MOF-919) for removing phospholipids from blood samples, wherein the chemical formula of MOF-919 is [Sc3(μ3-O)(OH)3][Cu3(μ3-O)(μ-PyC)3(H2O)6]2; the metal-organic framework (MOF-919) is obtained by a preparation method comprising the following steps: dissolving a Sc(III) salt and / or its hydrate, a Cu(II) salt and / or its hydrate, and a ligand 1H-pyrazole-4-carboxylic acid (H2PyC) in a polar aprotic solvent, heating and cooling the mixture, and sequentially exchanging the resulting green crystals between a polar aprotic solvent and an alcohol solvent, and drying; the amounts of Sc(III) salt, Cu(II) salt, and 1H-pyrazole-4-carboxylic acid are such that the molar ratio of Sc:Cu:1H-pyrazole-4-carboxylic acid is 1-1.2:2-2.5:2-3.

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