Preparation Method and Application of a Magnetic Imprint Polymer

Abstract

The present invention provides a preparation method and application of a magnetic imprinted polymer, which includes mixing the vinylated Fe3O4 microspheres, virtual template, functional monomer, and porogen, standing still to form a prepolymer, and then carrying out a polymerization reaction with a crosslinking agent and an initiator. The product is ground, the template is removed, and then vacuum dried to obtain the magnetic imprinted polymer. The magnetic imprinted polymer prepared by the present invention has high affinity and specific adsorption for nitroimidazole drugs, and has broad application potential as a magnetic dispersive solid-phase extraction material for the pretreatment of environmental samples and animal food matrices.

Description

Technical Field

[0001] The present invention belongs to the field of polymer materials, and particularly relates to a preparation method and application of a magnetic imprinted polymer. Background Art

[0002] Nitroimidazoles (NMZs) are a class of antibacterial drugs with a nitroheterocyclic structure, mainly including metronidazole, dimetridazole, ronidazole, tinidazole, ornidazole, etc., and are widely used in the livestock and poultry breeding industry to prevent and treat anaerobic infections and protozoal diseases. This class of drugs has risks of mutagenicity and potential carcinogenicity to human cells, and their metabolites formed in the organism also have toxic effects similar to those of the original drug. Now, many drugs have been listed in the prohibited drug list by countries such as the United States and the European Union. In China, metronidazole and dimetridazole are listed as veterinary drugs that are allowed for therapeutic use but shall not be detected in animal-derived foods in GB 31650-2019. The 250th announcement of the Ministry of Agriculture and Rural Affairs clearly stipulates that the use of ronidazole and tinidazole is prohibited in all food animals.

[0003] At present, the main detection methods for NMZs include enzyme-linked immunosorbent assay (ELISA), capillary electrophoresis (CE), gas chromatography-mass spectrometry (GC-MS), high performance liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (HPLC-MS / MS), etc. Currently, there are many studies on the residue detection technology of NMZs in animal-derived food matrices such as milk, livestock and poultry, and eggs. However, the current reported sample pretreatment methods for NMZs detection all adopt improved QuEChERS and traditional solid-phase extraction cartridges (such as MCX, HLB / C18) purification technologies, and it is urgent to improve the disadvantages of the above purification technologies such as lack of selectivity and poor specificity, so as to improve the sensitivity and quantitative accuracy of the instrument detection method.

[0004] Molecular imprinting technology is a rapidly developing research field based on the theory of molecular recognition. The obtained imprinted polymer can selectively rebind the template molecule and its analogues. This technology has been applied to the separation and enrichment of metal ions, organic small molecules, and even polypeptides and proteins, and has shown good prospects in molecular recognition, enrichment, separation, and detection. In recent years, the combination of magnetic nanoparticles and molecular imprinting technology has become a new research hotspot in this field, with the advantages of strong recognition specificity, high adsorption selectivity, efficient separation, and renewable utilization. Molecular imprinted polymers have the advantage of specific recognition of the target substance, and at the same time, the superparamagnetism of magnetic nanoparticles themselves can achieve rapid separation in an external magnetic field environment, improving the separation efficiency of adsorbing the target substance, saving analysis time and detection costs. Therefore, it is necessary to propose a magnetic imprinting technology with high selectivity and specific recognition of nitroimidazole drugs for magnetic dispersive solid-phase extraction purification and determination of nitroimidazole drugs. Summary of the Invention

[0005] The present invention aims to overcome the technical defects existing in the purification method of solid-phase extraction pretreatment in the detection of nitroimidazole drugs. To this end, a magnetic imprinted polymer is proposed in the first aspect of the present invention, which can highly selectively and specifically recognize nitroimidazole drugs and can be applied to the magnetic dispersive solid-phase extraction purification and analysis determination of such drugs.

[0006] A preparation method of such a magnetic imprinted polymer is proposed in the second aspect of the present invention.

[0007] An application of such a magnetic imprinted polymer is proposed in the third aspect of the present invention.

[0008] According to the first aspect of the present invention, a magnetic imprinted polymer is proposed. The raw materials of the magnetic imprinted polymer include: vinylated Fe3O4 microspheres, virtual template, functional monomer, crosslinking agent, porogen, initiator; the Fe3O4 microspheres include Fe3O4 and a SiO2 layer coating Fe3O4.

[0009] In some embodiments of the present invention, the virtual template is 4-methyl-5-nitroimidazole.

[0010] In some embodiments of the present invention, the polymer is spherical or quasi-spherical, and the average particle size is 54 μm to 75 μm.

[0011] In some embodiments of the present invention, the functional monomer is selected from at least one of 2-vinylpyridine, methacrylic acid, acrylic acid, 4-vinylpyridine or acrylamide.

[0012] In some embodiments of the present invention, the crosslinking agent is selected from at least one of ethylene glycol dimethacrylate, trimethylolpropane trimethacrylate, divinylbenzene.

[0013] In some embodiments of the present invention, the initiator can be a commonly used water-soluble initiator or oil-soluble initiator in the art, such as azobisisobutyronitrile, ammonium persulfate.

[0014] In some embodiments of the present invention, the porogen is selected from at least one of methanol, acetonitrile, chloroform, acetone.

[0015] In some preferred embodiments of the present invention, the porogen is methanol.

[0016] In the present invention, the porogen should ensure that the template molecules can be fully dissolved. The amount of the porogen also affects the adsorption parameters such as the hardness and surface characteristics of the synthesized imprinted polymer. At the same time, the porogen is also crucial for the polymer imprint recognition of nitroimidazole drugs in different use medium systems. Therefore, the results of the optimization experiment on the type of porogen show that: choosing methanol as the porogen, the prepared magnetic imprinted polymer has the strongest recognition specificity and adsorption selectivity for nitroimidazole drugs.

[0017] According to the second aspect of the present invention, a method for preparing a magnetic imprinted polymer is provided, including: mixing the vinylated Fe3O4 microspheres, virtual template, functional monomer, and porogen, standing still to form a prepolymer, and then carrying out a polymerization reaction with a crosslinking agent and an initiator. The product is ground into powder, and after removing the template, it is dried to obtain the magnetic imprinted polymer.

[0018] In some embodiments of the present invention, the magnetic imprinted polymer is prepared by bulk polymerization.

[0019] In some embodiments of the present invention, the ratio of the vinylated Fe3O4, virtual template, functional monomer, crosslinking agent, porogen, and initiator is (10 - 300) g : (1 - 5) mol : (2 - 20) mol : (10 - 40) mol : (2 - 30) L : (10 - 80) g.

[0020] In some preferred embodiments of the present invention, the ratio of the vinylated Fe3O4, virtual template, functional monomer, crosslinking agent, porogen, and initiator is (50 - 200) g : (2 - 5) mol : (3 - 15) mol : (15 - 30) mol : (2 - 20) L : (40 - 80) g.

[0021] In some preferred embodiments of the present invention, the standing still time is 1 h to 2 h.

[0022] In some preferred embodiments of the present invention, the temperature of the polymerization reaction is 50 °C to 80 °C.

[0023] In some preferred embodiments of the present invention, the time of the polymerization reaction is 24 h to 48 h.

[0024] In some preferred embodiments of the present invention, the product after grinding also needs to be sieved.

[0025] In some preferred embodiments of the present invention, the removal of the template is to repeatedly wash with methanol containing 10% by volume of acetic acid, and then wash with pure methanol to remove acetic acid.

[0026] In some preferred embodiments of the present invention, the drying is vacuum drying, the temperature is 50°C to 70°C, and the time is 8 h to 12 h.

[0027] In some more preferred embodiments of the present invention, the preparation method of the vinylated Fe3O4 microspheres comprises: firstly, coating a SiO2 layer on the surface of Fe3O4 to form Fe3O4@SiO2, and then further modifying the surface of Fe3O4@SiO2 with γ-methacryloxypropyltrimethoxysilane (KH-570) to obtain vinylated Fe3O4 microspheres (Fe3O4@SiO2@KH-570).

[0028] According to the third aspect of the present invention, there is provided an application of such a magnetic imprinted polymer in the detection of nitroimidazole drugs.

[0029] In some embodiments of the present invention, the magnetic imprinted polymer serves as a magnetic dispersive solid-phase extraction enrichment and purification material for nitroimidazole drugs.

[0030] In some preferred embodiments of the present invention, the magnetic imprinted polymer serves as a magnetic dispersive solid-phase extraction enrichment and purification material for pre-treating nitroimidazole drugs in environmental samples or animal food matrices.

[0031] The beneficial effects of the present invention are as follows:

[0032] 1. The preparation method of the present invention can directly add a crosslinking agent and an initiator to the prepolymer, and carry out a thermal polymerization curing reaction at 50°C to 80°C, thereby further improving the recognition specificity of the molecularly imprinted polymer.

[0033] 2. The magnetic imprinted polymer of the present invention shows significant affinity and high adsorption capacity for nitroimidazole drugs in solutions such as methanol and acetonitrile.

[0034] 3. The high selectivity of the magnetic imprinted polymer prepared by the present invention using 4-methyl-5-nitroimidazole as a virtual template for nitroimidazole drugs can effectively solve the "template leakage" problem and avoid background interference of the bulk template compound on detection.

[0035] 4. The magnetic imprinted polymer prepared by the present invention has potential application prospects as a magnetic dispersive solid-phase extraction enrichment and purification material for detecting nitroimidazole drugs in sample matrices such as environmental water samples and animal-derived foods.

[0036] 5. After being recycled 10 times, the adsorption recovery rate of the magnetic imprinted polymer prepared by the present invention for nitroimidazole drugs is still greater than 84.1%, and the adsorption performance is stable and excellent, having the potential for recycling. Description of the Drawings

[0037] The present invention will be further described below in conjunction with the accompanying drawings and embodiments, where:

[0038] Figure 1 It is a graph showing the adsorption and detection results of the polymer prepared in Example 1 and Comparative Example 1 of the present invention for nitroimidazole drugs.

[0039] Figure 2 It is a comparative graph of the adsorption effects of the polymers prepared in Example 1 and Comparative Example 1 of the present invention for nitroimidazole drugs in methanol solution.

[0040] Figure 3 It is a comparative graph of the adsorption effects of the polymers prepared in Example 2 and Comparative Example 1 of the present invention for nitroimidazole drugs in acetonitrile solution.

[0041] Figure 4 It is a comparative graph of the adsorption effects of the polymers prepared in Example 3 and Comparative Example 1 of the present invention for nitroimidazole drugs in river water samples.

[0042] Figure 5 It is a static adsorption test graph of the polymers prepared in Example 1 and Comparative Example 1 of the present invention for nitroimidazole drugs. Detailed implementation manners

[0043] The concept of the present invention and the technical effects produced will be clearly and completely described below in conjunction with the embodiments to fully understand the purpose, features and effects of the present invention. Obviously, the described embodiments are only a part of the embodiments of the present invention, rather than all the embodiments. Based on the embodiments of the present invention, other embodiments obtained by those skilled in the art without creative efforts shall fall within the scope of protection of the present invention.

[0044] Example 1

[0045] In this example, a magnetic imprinted polymer (m-MIPs A) was prepared. The specific process is as follows:

[0046] (1) Vinyl modification on the surface of Fe3O4

[0047] 0.1 g of Fe3O4 was dispersed in absolute ethanol, 4 mL of ammonia water was added, 4 mL of tetraethyl orthosilicate and 4 mL of absolute ethanol were slowly mixed and added dropwise, and mechanical stirring was carried out at a speed of 100 rpm. It was allowed to react fully at room temperature for 24 h. Fe3O4@SiO2 was separated by a strong rubidium magnet, ultrasonically cleaned with absolute ethanol and ultrapure water, and dried for later use. In a three-necked flask, 0.1 g of Fe3O4@SiO2, 50 mL of toluene and 2 mL of γ-methacryloxypropyltrimethoxysilane were added in sequence, nitrogen protection was introduced, and the reaction was carried out at the reflux temperature with heating and stirring for 24 h. Finally, the vinylated Fe3O4 was separated by a strong rubidium magnet, ultrasonically washed with absolute ethanol and ultrapure water, and dried for later use.

[0048] (2) Prepolymerization reaction

[0049] Accurately weigh 100 mg of vinylated Fe3O4 magnetic microspheres and 254.1 mg (2 mmol) of 4-methyl-5-nitroimidazole as the virtual template in a test tube respectively. Add 5 mL of methanol, vortex to dissolve, then add 0.434 mL (4 mmol) of 2-vinylpyridine functional monomer, sonicate for 5 min, and let stand for 1 h to form the prepolymerization reaction product.

[0050] (3) Polymerization and curing reaction

[0051] Add 4 mL (20 mmol) of ethylene glycol dimethacrylate and 60 mg of azobisisobutyronitrile to the above prepolymerization product, sonicate for 5 min, purge with nitrogen for 5 min, polymerize in a 60 °C vacuum drying oven for 24 h. Grind and crush the product, pass through a 100-mesh sieve and a 200-mesh sieve in sequence, repeatedly sediment with methanol to remove fine particles, put it into a 500 mL beaker, use 2000 mL of 10% acetic acid methanol solution, ultrasonically wash 3 - 5 times repeatedly to remove the virtual template molecules, then ultrasonically wash with 200 mL of methanol in several times to remove acetic acid, place it in a vacuum drying oven, dry at 60 °C for 8 h, and obtain the magnetic polymer and store it sealed in a desiccator.

[0052] Example 2

[0053] This example prepared a magnetic imprinted polymer (m-MIPs B), and the specific process is as follows:

[0054] (1) Vinyl modification of the Fe3O4 surface

[0055] Disperse 0.1 g of Fe3O4 in absolute ethanol, add 4 mL of ammonia water, slowly mix and dropwise add 4 mL of tetraethyl orthosilicate and 4 mL of absolute ethanol, mechanically stir at a speed of 100 rpm, and let it react fully at room temperature for 24 h. Separate Fe3O4@SiO2 with a strong rubidium magnet, ultrasonically clean with absolute ethanol and ultrapure water, and dry for later use. Add 0.1 g of Fe3O4@SiO2, 50 mL of toluene and 2 mL of γ-methacryloxypropyltrimethoxysilane to a three-necked flask in sequence, protect with nitrogen, heat and stir under reflux, react at 100 °C for 24 h. Finally, separate the vinylated Fe3O4 with a strong rubidium magnet, ultrasonically wash with absolute ethanol and ultrapure water, and dry for later use.

[0056] (2) Prepolymerization reaction

[0057] Accurately weigh 150 mg of vinylated Fe3O4 magnetic microspheres and 508.2 mg (4 mmol) of 4-methyl-5-nitroimidazole as the virtual template in a test tube respectively. Add 4 mL of methanol, vortex to dissolve, then add 0.651 mL (6 mmol) of 2-vinylpyridine functional monomer, sonicate for 5 min, and let stand for 1 h to form the prepolymerization reaction product.

[0058] (3) Polymerization and curing reaction

[0059] Add 6 mL (30 mmol) of ethylene glycol dimethacrylate and 80 mg of azobisisobutyronitrile to the above prepolymerization product, sonicate for 5 min, purge with nitrogen for 5 min, polymerize in a vacuum drying oven at 70 °C for 36 h. Grind and crush the product, pass through a 100-mesh sieve and a 200-mesh sieve in sequence, repeatedly sediment with methanol to remove fine particles, load into a 500 mL beaker, use 2000 mL of 10% acetic acid methanol solution, ultrasonically wash repeatedly 3 - 5 times to remove the virtual template molecules, then ultrasonically wash with 200 mL of methanol in portions to remove acetic acid, place in a vacuum drying oven, dry at 60 °C for 12 h, and obtain the magnetic polymer, which is sealed and stored in a desiccator.

[0060] Example 3

[0061] In this example, a magnetic imprinted polymer (m-MIPs C) was prepared. The specific process is as follows:

[0062] (1) Vinyl modification of the Fe3O4 surface

[0063] Disperse 0.1 g of Fe3O4 in anhydrous ethanol, add 4 mL of ammonia water, slowly mix and dropwise add 4 mL of tetraethyl orthosilicate and 4 mL of anhydrous ethanol, mechanically stir at a speed of 100 rpm / min, and allow it to react fully at room temperature for 24 h. Separate Fe3O4@SiO2 with a strong rubidium magnet, ultrasonically clean with anhydrous ethanol and ultrapure water, and dry for later use. Add 0.1 g of Fe3O4@SiO2, 50 mL of toluene and 2 mL of γ-methacryloxypropyltrimethoxysilane to a three-necked flask in sequence, protect with nitrogen, heat and stir under reflux, react at 100 °C for 24 h. Finally, separate the vinylated Fe3O4 with a strong rubidium magnet, ultrasonically wash with anhydrous ethanol and ultrapure water, and dry for later use.

[0064] (2) Prepolymerization reaction

[0065] Accurately weigh 200 mg of vinylated Fe3O4 magnetic microspheres and 635.5 mg (5 mmol) of 4-methyl-5-nitroimidazole as the virtual template in a test tube respectively. Add 10 mL of methanol, vortex to dissolve, then add 0.868 mL (8 mmol) of 2-vinylpyridine functional monomer, sonicate for 5 min, and let stand for 2 h to form the prepolymerization reaction product.

[0066] (3) Polymerization and curing reaction

[0067] 6 mL (30 mmol) of ethylene glycol dimethacrylate and 80 mg of azobisisobutyronitrile were added to the above prepolymer. After ultrasonic treatment for 5 min and nitrogen gas introduction for 5 min, polymerization was carried out in a vacuum drying oven at 80 °C for 48 h. The product was ground and crushed, passed through a 100-mesh sieve and a 200-mesh sieve in sequence, and small particles were removed by repeated sedimentation with methanol. It was placed in a 500 mL beaker, and 2000 mL of 10% acetic acid methanol solution was used to ultrasonically wash and remove the template molecules 3 - 5 times repeatedly. Then, it was ultrasonically washed with 200 mL of methanol in portions to remove acetic acid, placed in a vacuum drying oven, dried at 60 °C for 12 h, and the magnetic polymer was obtained and stored sealed in a desiccator.

[0068] Comparative Example 1

[0069] In this comparative example, a magnetic non-imprinted polymer (m-NIPs A) was prepared. The difference from Example 1 was that no dummy template was added during the preparation process, and the rest was carried out with reference to Example 1.

[0070] Test Example

[0071] Adsorption and detection of nitroimidazole drugs by the polymers prepared in Examples 1 - 3 and Comparative Example 1

[0072] 150 mg of m-MIPs prepared in Examples 1 - 3 and m-NIPs prepared in Comparative Example 1 (particle size 54 μm - 75 μm) were weighed separately into 15 mL polyacrylamide centrifuge tubes and washed with 3 mL of 5% (v / v) acetic acid methanol. Then, they were successively balanced and activated with 3 mL of methanol and 3 mL of water, and separated by an external magnetic field, and the liquid was poured out and discarded.

[0073] A series of mixed standard solutions of nitroimidazole drugs with concentrations of 0.1, 0.5, 2.0, and 20 μg / mL were obtained by diluting with methanol as test sample solutions. 5 mL of each was separately pipetted and transferred to centrifuge tubes containing the activated m-MIPs prepared in Example 1 and m-NIPs prepared in Comparative Example 1, vortex-mixed evenly, and allowed to stand for an adsorption reaction for 30 min. After separation by an external magnetic field, the reaction sample solution was discarded, and the magnetic polymer was washed with 5 mL of water and 5 mL of methanol. Finally, it was eluted with 3 mL of 80% methanol - formic acid - aqueous solution (80:0.5:20, v / v / v). The eluate was carefully blown dry with nitrogen until nearly dry, dissolved with 20% methanol - aqueous solution, centrifuged at high speed, and passed through a 0.22 μm microporous filter membrane for LC-MS / MS detection. The results are as Figure 1As shown in the figure, where MNZOH: hydroxy metronidazole; HMMNI: hydroxymethyl metronidazole; MNZ: metronidazole; RNZ: ronidazole; DMZ: dimetridazole; SNZ: secnidazole; IPZ: ipronidazole; IPZOH: hydroxy ipronidazole; ONZ: ornidazole; CNZ: canidazole; m-MIPs: magnetic imprinted polymers; m-NIPs: magnetic non-imprinted polymers.

[0074] The experimental results show that the m-MIPs A prepared in Example 1 was successfully applied to the magnetic dispersive solid-phase extraction of 10 nitroimidazole drugs, and the adsorption recovery rate was 91.8% - 104%. The adsorption recovery rate of the m-NIPs A prepared in Comparative Example 1 for nitroimidazole drugs was between 33.6% - 47.5% (see Figure 2 ).

[0075] The mixed standard solutions of nitroimidazole drugs with serial concentrations of 0.1, 0.5, 2.0 and 20 μg / mL were diluted with acetonitrile as the test sample solutions. 5 mL of each was respectively transferred to centrifuge tubes containing the activated m-MIPs B prepared in Example 2 and m-NIPs A prepared in Comparative Example 1, vortex-mixed evenly, and allowed to stand for adsorption reaction for 30 min. Separated by an external magnetic field, the reaction sample solution was discarded, the magnetic polymer was washed with 5 mL of water and 5 mL of methanol, and finally eluted with 3 mL of 80% methanol-formic acid-aqueous solution (80:0.5:20, v / v / v). The eluate was carefully blown dry with nitrogen until nearly dry, dissolved with 20% methanol-aqueous solution, centrifuged at high speed, and passed through a 0.22 μm microporous filter membrane for LC-MS / MS detection.

[0076] The results are as Figure 3 shown. The m-MIPs B prepared in Example 2 was successfully applied to the magnetic dispersive solid-phase extraction of 10 nitroimidazole drugs in acetonitrile solution, and the adsorption recovery rate was 94.1% - 107%. The adsorption recovery rate of the m-NIPs A prepared in Comparative Example 1 for nitroimidazole drugs in acetonitrile solution was between 35.2% - 46.8%.

[0077] 5 mL of river water with the final concentrations of the mixed standard solutions of nitroimidazole drugs being 0.1, 0.5, 2.0 and 20 μg / mL were respectively transferred to centrifuge tubes containing the activated m-MIPs C prepared in Example 3 and m-NIPs A prepared in Comparative Example 1, vortex-mixed evenly, and allowed to stand for adsorption reaction for 30 min. Separated by an external magnetic field, the reaction sample solution was discarded, the magnetic polymer was washed with 5 mL of water and 5 mL of methanol, and finally eluted with 3 mL of 80% methanol-formic acid-aqueous solution (80:0.5:20, v / v / v). The eluate was carefully blown dry with nitrogen until nearly dry, dissolved with 20% methanol-aqueous solution, centrifuged at high speed, and passed through a 0.22 μm microporous filter membrane for LC-MS / MS detection.

[0078] The results are as Figure 4 shown. The m-MIPs C prepared in Example 3 was successfully applied to the magnetic dispersive solid-phase extraction of 10 nitroimidazole drugs in river water samples, and the adsorption recovery rates were all greater than 92.7%; the adsorption recovery rates of the m-NIPs A prepared in Comparative Example 1 for nitroimidazole drugs in river water samples were all lower than 46.5%.

[0079] The m-MIPs A prepared in Example 1 was used in the static adsorption test of 10 nitroimidazole drugs. According to the changes in the concentrations of each drug in the solution at different time points, the adsorption amount was calculated. The maximum adsorption amounts of the 10 nitroimidazole drugs were approximately 2.91 - 6.72 mg / g polymer (see Figure 5 ). This indicates that the magnetic imprinted polymer prepared by the present invention has group-specific recognition and high affinity for the adsorption of nitroimidazole drugs.

[0080] After the m-MIPs A prepared in Example 1 was separated by an external magnetic field and reused 10 times, the adsorption recovery rate for nitroimidazole drugs was still greater than 84.1%. This shows that the magnetic material has stable and excellent adsorption performance and has the potential for recycling.

[0081] The above has described the embodiments of the present invention in detail. However, the present invention is not limited to the above embodiments. Within the scope of knowledge possessed by those of ordinary skill in the art, various changes can be made without departing from the purpose of the present invention. In addition, without conflict, the embodiments of the present invention and the features in the embodiments can be combined with each other.

Claims

1. A magnetic imprinting polymer, characterized in that, The raw materials of the magnetic imprinted polymer include: vinylated Fe3O4 microspheres, virtual template, functional monomer, crosslinking agent, porogen, initiator; the Fe3O4 microspheres include Fe3O4 and a SiO2 layer coating Fe3O4; the virtual template is 4-methyl-5-nitroimidazole.

2. The magnetic imprinted polymer according to claim 1, wherein The functional monomer is selected from at least one of 2-vinylpyridine, methacrylic acid, acrylic acid, 4-vinylpyridine or acrylamide.

3. The preparation method of the magnetic imprinted polymer according to any one of claims 1 to 2, characterized in that, It includes: Mix the vinylated Fe3O4 microspheres, virtual template, functional monomer, and porogen, let it stand still to form a prepolymer, then carry out a polymerization reaction with the crosslinking agent and initiator, grind the product, remove the template, and dry it to obtain the magnetic imprinted polymer.

4. The preparation method according to claim 3, wherein, The ratio of the vinylated Fe3O4 microspheres, virtual template, functional monomer, crosslinking agent, porogen and initiator is (10 - 300) g : (1 - 5) mol﹕(2 - 20) mol﹕(10 - 40) mol﹕(2 - 30) L﹕(10 - 80) g.

5. The preparation method according to claim 3, characterized in that, The temperature of the polymerization reaction is 50°C to 80°C.

6. The preparation method according to claim 3, characterized in that, The time of the polymerization reaction is 24 h to 48 h.

7. The preparation method according to claim 3, characterized in that, The preparation method of the vinylated Fe3O4 microspheres includes: first coat a SiO2 layer on the surface of Fe3O4 to form Fe3O4@SiO2, and then carry out vinylation modification on Fe3O4@SiO2 with γ-methacryloxypropyltrimethoxysilane to obtain vinylated Fe3O4 microspheres.

8. The preparation method according to claim 3, characterized in that, The temperature of the drying is 50°C to 70°C, and the time is 8 h to 12 h.

9. Use of the magnetic imprinted polymer according to any one of claims 1 to 2 in detecting nitroimidazole drugs.

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