Magnetic organic polymers for the enrichment and extraction of macrolide antibiotics, their preparation methods and applications

Abstract

This invention discloses a magnetic organic polymer for the enrichment and extraction of macrolide antibiotics, its preparation, and its application. The magnetic organic polymer has a core-shell structure, with magnetic Fe3O4 nanoparticles as the core and a Tb-PDAN organic polymer formed by the reaction of trimesin and terephthalonitrile as the shell. This magnetic organic polymer can be used as an adsorbent for the enrichment and extraction of macrolide antibiotics in water, enabling qualitative and / or quantitative detection of macrolide antibiotics. The magnetic organic polymer of this invention can simultaneously, rapidly, and efficiently extract 16 macrolide antibiotics from water and is reusable, making it of significant importance for advancing the monitoring of macrolide antibiotics in water.

Description

Technical Field

[0001] This invention relates to the field of antibiotic enrichment and extraction technology, specifically to a magnetic organic polymer for the enrichment and extraction of macrolide antibiotics, as well as the preparation method and application of the magnetic organic polymer. Background Technology

[0002] Antibiotics are widely used in the feeding of livestock, poultry, and aquatic products because they can prevent and treat bacterial infections and accelerate animal growth. However, because they cannot be completely absorbed by organisms, excessive amounts are excreted in the feces and urine of animals in their original form. Furthermore, due to misuse and abuse in recent years, antibiotics are entering the environment at a rate exceeding their degradation rate, damaging ecosystems and exacerbating environmental pollution, especially water resources. This is because traditional water treatment processes cannot effectively remove antibiotic compounds, causing serious harm to aquatic organisms and human health.

[0003] The types and quantities of antibiotics used are increasing year by year. In 2010, macrolides ranked third in global antibiotic consumption. Macrolide antibiotics have strong toxicity to animals and have been proven to have certain carcinogenic effects. In addition, residual macrolide antibiotics in the environment can induce the development of allergic reactions and the emergence of drug-resistant bacteria. Therefore, the detection of macrolide antibiotic residues in environmental water samples is very important. The main sources of antibiotics in environmental water samples are industrial wastewater, hospital wastewater, and sewage treatment effluent. Due to the large total amount of effluent, the amount of antibiotics to be detected in environmental water samples is often small. Therefore, separating and enriching macrolide antibiotics in water samples before detection is a crucial step and is key to ensuring the accuracy of the test results.

[0004] Currently, sample pretreatment generally employs methods such as liquid-liquid extraction or solid-phase extraction. Liquid-liquid extraction consumes large amounts of organic reagents, leading to secondary pollution and waste disposal issues. Traditional solid-phase extraction is not only complex to operate but also incurs high detection costs due to the use of some commercially available solid-phase extraction columns, limiting its application. The separation and recovery of materials during solid-phase extraction are key technical aspects, which to some extent restricts its wider application. With the development of solid adsorbent materials such as graphene, metal-organic frameworks, molecularly imprinted polymers, and other organic polymers, researchers have introduced Fe3O4 magnetic particles into adsorbent materials to establish magnetic solid-phase extraction technology. This novel solid-phase extraction technology has attracted widespread attention in sample pretreatment due to its ease of operation, fewer steps, time-saving characteristics, and reusability. Developing novel magnetic materials that combine stability, selectivity, and ease of separation is the core of magnetic solid-phase extraction technology. Currently, there are few reports on the use of magnetic organic polymers to extract macrolide antibiotics from water. Therefore, developing novel magnetic materials that can rapidly and efficiently extract various macrolide antibiotics from water, and achieving rapid, accurate, and efficient sample pretreatment, is of great significance for improving detection capabilities. Summary of the Invention

[0005] To address the shortcomings of existing technologies, this invention provides a novel magnetic organic polymer for the enrichment and extraction of macrolide antibiotics. This material can form various interactions with the target compound, enabling the simultaneous extraction of 16 macrolide antibiotics, thus meeting the need for rapid separation and analysis of multiple macrolide antibiotics in water samples.

[0006] To achieve the above objectives, the present invention provides a magnetic organic polymer for the enrichment and extraction of macrolide antibiotics, which has a core-shell structure, with magnetic Fe3O4 nanoparticles as the core and Tb-PDAN organic polymer formed by the reaction of trimesin and terephthalonitrile as the shell; the magnetic organic polymer has a planar conjugated structure and also contains nitrogen elements with lone pairs of electrons.

[0007] As a limitation of the above technical solution, the magnetic organic polymer is formed by first coating SiO2 on the surface of Fe3O4 nanoparticles to form Fe3O4@SiO2 particles, and then coating them with the shell material Tb-PDAN organic polymer.

[0008] Given the problem of easy agglomeration of nano-Fe3O4 particles, coating their surface with SiO2 first can improve the dispersibility of Fe3O4 and the uniformity of the coating shell material.

[0009] This invention utilizes an organic polymer formed by the reaction of trimesin and terephthalonitrile as a shell material to encapsulate magnetic Fe3O4 nanoparticles, constructing a magnetic adsorption material Fe3O4@SiO2@Tb-PDAN for the enrichment and extraction of macrolide antibiotics from water. This material contains cyano groups and benzene rings. The cyano group, an electron-rich group, can form a conjugation with the benzene ring, increasing the electron cloud density and facilitating strong intermolecular forces between the material and macrolide antibiotics, thereby promoting adsorption. Furthermore, the structure of Fe3O4@SiO2@Tb-PDAN also contains hydrocarbon groups, and the proportion of hydrocarbon groups is relatively large, thus exhibiting hydrophobicity. Based on the principle of "like dissolves like," macrolide antibiotics and Fe3O4@SiO2@Tb-PDAN interact more readily in an aqueous environment, which is more conducive to the stable adsorption of target compounds, achieving highly efficient enrichment and extraction of macrolide antibiotics and improving current detection levels.

[0010] As a limitation of the above technical solution, the magnetic organic polymer is prepared by placing Fe3O4@SiO2 particles, pyromellitic methyl methacrylate, terephthalonitrile, and 1,8-diazabicyclo[5.4.0]undec-7-ene (DBU) in a tetrahydrofuran solvent, followed by ultrasonic mixing and reflux reaction.

[0011] Fe3O4@SiO2, pyromellitic aldehyde and terephthalonitrile were used as raw materials, tetrahydrofuran was used as solvent, and DBU was used as catalyst. The reaction was carried out at reflux temperature.

[0012] In the core-shell structure formation reaction, pyromellitic aldehyde and terephthalonitrile are used as raw materials for the shell structure, tetrahydrofuran is used as solvent, and DBU is used as catalyst. At reflux temperature, the aldehyde and cyano groups react to generate a polymer with carbon-carbon double bonds, which uniformly encapsulates Fe3O4@SiO2, constructing a magnetic organic polymer that can form π conjugated bonds with macrolide antibiotics to produce strong adsorption. It is also easy to separate and subsequently desorb, realizing the efficient enrichment, extraction and separation analysis of macrolide antibiotics.

[0013] As a limitation of the above technical solution, the magnetic organic polymer can simultaneously extract 16 kinds of macrolide antibiotics.

[0014] The magnetic organic polymer of this invention can simultaneously extract multiple macrolide antibiotics from water. Compared with existing adsorption materials used for the enrichment and extraction of macrolide antibiotics, it has the significant advantages of simultaneously extracting more types of antibiotics and achieving a higher enrichment and extraction rate.

[0015] Meanwhile, the present invention also provides a method for preparing the magnetic organic polymer used for the enrichment and extraction of macrolide antibiotics as described above, comprising the following steps:

[0016] (1) Obtain spherical magnetic Fe3O4 nanoparticles, wash and vacuum dry them for later use;

[0017] (2) SiO2 was coated on the surface of magnetic Fe3O4 nanoparticles to obtain Fe3O4@SiO2 particles;

[0018] (3) Fe3O4@SiO2 particles, pyromellitic aldehyde, terephthalic acid nitrile and DBU were placed in tetrahydrofuran solvent and ultrasonically mixed to allow the mixture to react fully at reflux temperature. The product was then washed and dried after magnetic separation to obtain the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN.

[0019] The synthesis reaction of the magnetic organic polymer of this invention does not require a vacuum environment, and the operation is simple and convenient. The obtained polymer has a stable structure, strong adsorption, and high enrichment and extraction efficiency, which is conducive to the promotion and application of the polymer.

[0020] As a limitation of the above technical solution, step (1) uses a solvothermal method to prepare spherical magnetic Fe3O4 nanoparticles, specifically including the following steps:

[0021] FeCl3·6H2O was dissolved in ethylene glycol, and then PEG-4000 and CH3COONa·3H2O were added and stirred thoroughly. The mixture was then reacted at 200±5℃ for 7-9 hours. The product was washed with anhydrous ethanol and then dried under vacuum at 60±5℃ to obtain spherical magnetic Fe3O4 nanoparticles for use.

[0022] The mass ratio of FeCl3·6H2O, PEG-4000 and CH3COONa·3H2O is 1.6:(1.8~2.4):(7.0~7.4).

[0023] As a limitation of the above technical solution, step (2) uses tetraethyl orthosilicate hydrolysis to coat SiO2 on the surface of magnetic Fe3O4 nanoparticles, specifically including the following steps:

[0024] Magnetic Fe3O4 nanoparticles were added to an ethanol solution, ultrasonically dispersed, and then ammonia and tetraethyl orthosilicate were added. After hydrolysis, Fe3O4@SiO2 particles were obtained.

[0025] The ratio of the magnetic Fe3O4 nanoparticles, ethanol solution, ammonia, and tetraethyl orthosilicate is 0.1 g:(90-110) mL:(1.2-1.7) mL:(0.8-1.2) mL; the volume ratio of anhydrous ethanol to water in the ethanol solution is (3-6):1; the hydrolysis reaction conditions are heating and stirring at 25-32℃ for 20-26 h.

[0026] As a limitation of the above technical solution, in step (3), DBU is first dissolved in water to prepare a solution with a molar concentration of 5-7 mol / L and then added to tetrahydrofuran solvent; the ratio between the amounts of Fe3O4@SiO2 particles, pyromellitic aldehyde, terephthalonitrile and DBU solution is (85-120) mg: (0.24-0.32) mmol: 0.48 mmol: (2-3) mL;

[0027] After magnetic separation, the product was washed sequentially with anhydrous ethanol and ultrapure water, and then vacuum dried at 60±5℃ for 2-4 h to obtain the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN.

[0028] Further refine the preparation conditions of magnetic organic polymers to obtain magnetic adsorption materials with stable structure and significant advantages in enrichment and extraction effects.

[0029] Furthermore, the present invention also provides a method for using the magnetic organic polymer described above for the enrichment and extraction of macrolide antibiotics. The method involves using the magnetic organic polymer as an adsorbent to enrich and extract macrolide antibiotics in water, and enabling qualitative and / or quantitative detection of macrolide antibiotics.

[0030] The sample obtained by enriching and extracting macrolide antibiotics in water using the magnetic organic polymer of the present invention as an adsorbent can be used for various qualitative or quantitative analyses, such as capillary electrophoresis (CE), high performance liquid chromatography (HPLC), and liquid chromatography-tandem mass spectrometry (LC-MS / MS), which are commonly used to analyze and detect macrolide antibiotic residues. It is especially suitable for the LC-MS / MS method, which has the characteristics of good selectivity, high sensitivity, and high throughput, for the simultaneous detection of multiple macrolide antibiotics in water samples.

[0031] As a limitation of the above technical solution, the method of using the magnetic organic polymer for the enrichment and extraction of macrolide antibiotics specifically includes the following steps:

[0032] A magnetic organic polymer is added to a water sample containing macrolide antibiotics. After thorough mixing and extraction, the organic polymer is precipitated using an external magnetic field. The supernatant is then removed under the influence of the magnetic field. Finally, an eluent is added to the collected organic polymer to recover the analyte for qualitative and / or quantitative determination. The eluent is an ammonia-acetonitrile solution, with the volume percentage of ammonia in the ammonia-acetonitrile solution being 1-2%.

[0033] The magnetic organic polymer of this invention is used for the enrichment and extraction of macrolide antibiotics in water. The operation is simple, utilizing the strong magnetism and structural stability of the magnetic organic polymer. Through mixed extraction, separation and recovery under a magnetic field, and subsequent elution, the sample can be used for subsequent conventional detection methods. It exhibits strong and stable adsorption of target compounds, high enrichment and extraction rates, and convenient and efficient desorption, achieving high recovery rates for 16 macrolide antibiotics, with the highest recovery rate exceeding 98%. During the enrichment and extraction process, the adsorption extraction time is generally only 3–15 minutes, and the elution time is generally only 3–7 minutes, yielding samples suitable for subsequent detection. The operation is rapid and convenient, facilitating the rapid separation and analysis of multiple macrolide antibiotics in water samples. The magnetic organic polymer of this invention also has the advantage of good reusability, enabling efficient and practical detection.

[0034] In summary, the magnetic organic polymer of the present invention, used for the enrichment and extraction of macrolide antibiotics in water, has significant advantages such as high adsorption efficiency and simultaneous extraction of multiple antibiotic types, achieving the goal of rapid separation and enrichment of macrolide antibiotics from water samples; moreover, the preparation process of this polymer is simple, the product is stable, and the enrichment and extraction application is convenient, which is of great significance for improving detection capabilities. Attached Figure Description

[0035] Figure 1 This is a flowchart illustrating the preparation process of Fe3O4@SiO2@Tb-PDAN according to the present invention.

[0036] Figure 2 Scanning electron microscope (SEM) images of Fe3O4 nanoparticles (A) and Fe3O4@SiO2@Tb-PDAN (B) from Example 1; transmission electron microscope (TEM) images of Fe3O4 nanoparticles (C) and Fe3O4@SiO2@Tb-PDAN (D).

[0037] Figure 3 The infrared spectra of Fe3O4@SiO2 and Fe3O4@SiO2@Tb-PDAN in Example 1 are shown.

[0038] Figure 4 The magnetic properties of Fe3O4 and Fe3O4@SiO2@Tb-PDAN in Example 1 are characterized.

[0039] Figure 5 The image shows the adsorption effect of Fe3O4@SiO2@Tb-PDAN in Example 1 on the three-stage recovery and reuse of 16 macrolide antibiotics in a water sample. Detailed Implementation

[0040] The technical solution of the present invention will be clearly and completely described below with reference to the embodiments. Obviously, the described embodiments are only some embodiments of the present invention, and not all embodiments. Based on the embodiments of the present invention, all other embodiments obtained by those of ordinary skill in the art without creative effort are within the scope of protection of the present invention.

[0041] The chemical raw materials involved in the following examples and comparative examples are all typical products purchased from the market. Among them, ammonia water was purchased at a mass fraction of 25%, acetonitrile was chromatographically pure, and other chemical raw materials were analytically pure.

[0042] Example 1

[0043] The preparation process of the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN of the present invention is as follows: Figure 1 As shown, the specific operations include the following:

[0044] (1) Preparation of magnetic Fe3O4 nanoparticles: 1.6g FeCl3·6H2O was accurately weighed and dissolved in 60mL ethylene glycol. After being stirred and dissolved by a magnetic stirrer, 2.0g PEG-4000 and 7.2g CH3COONa·3H2O were added to the solution. After stirring for 30min, a brown turbid solution was obtained. The solution was transferred to a reaction vessel and reacted at 200℃ for 8h. The product was cleaned with anhydrous ethanol to obtain Fe3O4 nanoparticles, which were then vacuum dried at 60℃ for 3h.

[0045] (2) Preparation of Fe3O4@SiO2: Add 0.1g of Fe3O4 nanoparticles from step (1) to 100mL of ethanol solution, disperse by ultrasonication for 30min, then add 1.5mL of ammonia and 1.0mL of tetraethyl orthosilicate, and hydrolyze to obtain Fe3O4@SiO2 particles; the volume ratio of anhydrous ethanol to water in the ethanol solution is 4:1, and the hydrolysis reaction conditions are heating and stirring at 30℃ for 24h.

[0046] (3) Preparation of magnetic organic polymer Fe3O4@SiO2@Tb-PDAN: 100 mg Fe3O4@SiO2 particles were added to a round-bottom flask containing 20 mL tetrahydrofuran. After sonication for 5 min, 52 mg pyromellitic aldehyde (0.32 mmol), 75 mg terephthalonitrile (0.48 mmol) and 2 mL DBU solution (solvent is water, and the concentration of DBU in the solution is 6 mol / L) were added to the round-bottom flask in sequence. The reaction mixture was heated to reflux temperature and reacted for 24 h. The obtained product was magnetically separated and washed with anhydrous ethanol and ultrapure water respectively until the supernatant became clear. It was then vacuum dried at 60 °C for 3 h to obtain Fe3O4@SiO2@Tb-PDAN.

[0047] The obtained materials were characterized, and the results are as follows: Figures 2-4 As shown.

[0048] Figure 2 Images show scanning electron microscopy (SEM) and transmission electron microscopy (TEM) images of magnetic Fe3O4 nanoparticles and the magnetic polymer Fe3O4@SiO2@Tb-PDAN. Image A is an SEM image of Fe3O4 nanoparticles, image B is an SEM image of Fe3O4@SiO2@Tb-PDAN, image C is a TEM image of Fe3O4 nanoparticles, and image D is a TEM image of Fe3O4@SiO2@Tb-PDAN. The SEM images of the two types of nanoparticles show that the magnetic Fe3O4 nanoparticles have a spherical structure. Because nano-Fe3O4 particles are prone to aggregation, coating their surface with SiO2 first improves the dispersion of Fe3O4 and the uniformity of the coating material Tb-PDAN. The roughness of the coated Fe3O4@SiO2@Tb-PDAN particles is significantly increased, and there is obvious aggregation between particles, further proving that Tb-PDAN is successfully coated onto the Fe3O4 nanoparticles. TEM images of the two types of nanoparticles show that the Fe3O4 nanoparticles are basically uniform in shape, and the magnetic Fe3O4@SiO2@Tb-PDAN material has a distinct core-shell structure. The inner core is composed of Fe3O4 nanoparticles, while the outer shell is composed of Tb-PDAN generated by the reaction of trimesin and terephthalonitrile.

[0049] Figure 3 The infrared spectra of the magnetic materials Fe3O4@SiO2 and Fe3O4@SiO2@Tb-PDAN are shown at 577 and 1096 cm⁻¹. -1 The absorption peaks at 3436 cm⁻¹ represent the vibrations of Fe-O-Fe and Si-O-Si, respectively. -1 and 1632cm -1 The presence of water groups and hydroxyl groups adsorbed on the Fe3O4 surface indicates that Tb-PDAN was successfully coated onto Fe3O4@SiO2. Furthermore, Fe3O4@SiO2@Tb-PDAN exhibits high viscosity at 1612 cm⁻¹. -1 and 2212cm -1 New characteristic absorption peaks appear, attributed to -CN and C=C, respectively. Meanwhile, at 2937 cm⁻¹... -1 A signal belonging to -C=CH was observed at this location, further confirming the formation of C=C bonds. This demonstrates that Tb-PDAN was successfully coated onto the Fe3O4@SiO2 surface.

[0050] Figure 4The hysteresis curves of magnetic Fe3O4 nanoparticles and magnetic polymer Fe3O4@SiO2@Tb-PDAN are shown. The results show that the saturation magnetization of Fe3O4 is 82.94 emu / g, while that of Fe3O4@SiO2@Tb-PDAN is 35.84 emu / g. Although the magnetism of Fe3O4@SiO2@Tb-PDAN is significantly reduced compared to Fe3O4, it still exhibits superparamagnetism and can still achieve rapid separation under the action of an external magnetic field.

[0051] The magnetic polymer Fe3O4@SiO2@Tb-PDAN synthesized in this embodiment was used as an adsorbent to extract macrolide antibiotics from water samples.

[0052] Weigh 12 mg of Fe3O4@SiO2@Tb-PDAN and add it to 10 mL of a water sample containing 16 macrolide antibiotics (see Table 1-1 below, each antibiotic concentration is 2 ng / mL) at pH 8. (If the water sample is turbid, it can be filtered through a 0.45 μm nylon filter membrane or other methods, the same below). Vortex for 5 min, and use an external magnetic field to cause Fe3O4@SiO2@Tb-PDAN to settle. Remove the supernatant under the action of the magnetic field, then wash the Fe3O4@SiO2@Tb-PDAN. Add 6 mL of ammonia-acetonitrile solution to the collected Fe3O4@SiO2@Tb-PDAN. The ammonia solution in the ammonia-acetonitrile solution... The volume percentage was 1.2%. After vortexing for 5 min, the entire ammonia-acetonitrile solution was transferred to another centrifuge tube under an external magnetic field. 6 mL of the same ammonia-acetonitrile solution was added to Fe3O4@SiO2@Tb-PDAN, and the mixture was vortexed for 5 min. The ammonia-acetonitrile solution was then removed under an external magnetic field. The eluent from both washes was combined and vortexed. 6 mL of the eluent was dried under nitrogen and reconstituted with 1 mL of a mixed solution of acetonitrile and 0.1% formic acid water (0.1% being the volume percentage of formic acid in formic acid water, the same below) (where the volume ratio of acetonitrile to 0.1% formic acid water was 7:3, the same below). The solution was filtered through a 0.2 μm filter and then analyzed by LC-MS / MS. The enrichment effect of Fe3O4@SiO2@Tb-PDAN on 16 macrolide antibiotics was evaluated by calculating the recovery rate. The results are shown in Table 1-1.

[0053]

[0054]

[0055] As can be seen from the results in the table above, the recovery rate of the magnetic organic polymer in Example 1 for the enrichment and extraction of 16 macrolide antibiotics in water ranges from 71.54% to 98.29%, with a maximum of 98.29%.

[0056] In addition, the magnetic organic polymer prepared in Example 1 was used to enrich and extract sulfonamides, quinolones, and β-lactam antibiotics (see Table 1-2 below, each antibiotic concentration is 2 ng / mL) in water samples. The results showed that the magnetic organic polymer of the present invention only had a good enrichment and extraction effect on macrolide antibiotics, while it had almost no effect on other types of antibiotics, as shown in Table 1-2.

[0057]

[0058] Example 2

[0059] (1) Preparation of magnetic Fe3O4 nanoparticles: 1.6g FeCl3·6H2O was accurately weighed into 60mL ethylene glycol and dissolved by stirring with a magnetic stirrer. 1.9g PEG-4000 and 7.1g CH3COONa·3H2O were added to the solution and stirred for 30min to obtain a brown turbid solution. The solution was transferred to a reaction vessel and reacted at 200℃ for 7h. The product was cleaned with anhydrous ethanol to obtain Fe3O4 nanoparticles, which were then vacuum dried at 60℃ for 4h.

[0060] (2) Preparation of Fe3O4@SiO2: Add 0.1g of Fe3O4 nanoparticles from step (1) to 110mL of ethanol solution, disperse by ultrasonication for 30min, then add 1.3mL of ammonia and 0.9mL of tetraethyl orthosilicate, and hydrolyze to obtain Fe3O4@SiO2 particles. The volume ratio of anhydrous ethanol to water in the ethanol solution is 3:1, and the hydrolysis reaction is carried out under the condition of heating and stirring at 25℃ for 26h.

[0061] (3) Preparation of the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN: 85 mg of Fe3O4@SiO2 particles were first added to a round-bottom flask containing 20 mL of tetrahydrofuran. After sonication for 5 min, 45.5 mg of trimesin (0.28 mmol), 75 mg of terephthalonitrile (0.48 mmol), and 3 mL of DBU solution (water as solvent, DBU concentration in solution was 5 mol / L) were added to the round-bottom flask sequentially. The reaction mixture was heated to reflux temperature for 26 h. The obtained product was washed with anhydrous ethanol and ultrapure water until the supernatant became clear, and then dried under vacuum at 60 °C for 2 h to obtain Fe3O4@SiO2@Tb-PDAN. The microscopic characterization results of the obtained material showed that it was similar to the material obtained in Example 1.

[0062] The Fe3O4@SiO2@Tb-PDAN synthesized in this embodiment was used as an adsorbent to extract macrolide antibiotics from water samples.

[0063] Weigh 12 mg of Fe3O4@SiO2@Tb-PDAN and add it to 10 mL of a water sample with pH 7 containing 16 macrolide antibiotics (see Table 2 below, each antibiotic concentration is 2 ng / mL). Vortex for 15 min, and use an external magnetic field to cause Fe3O4@SiO2@Tb-PDAN to settle. Remove the supernatant under the action of the magnetic field, then wash the Fe3O4@SiO2@Tb-PDAN. Add 6 mL of ammonia-acetonitrile solution to the collected Fe3O4@SiO2@Tb-PDAN. The volume percentage of ammonia in the ammonia-acetonitrile solution is 2%. Vortex for 7 min. Under an external magnetic field, the entire ammonia-acetonitrile solution was transferred to another centrifuge tube. 6 mL of the same ammonia-acetonitrile solution was added to Fe3O4@SiO2@Tb-PDAN, and the mixture was vortexed for 7 min. The ammonia-acetonitrile solution was then removed under an external magnetic field. The eluent from both washes was combined and vortexed to mix. 6 mL of the eluent was dried under nitrogen and reconstituted with 1 mL of a mixture of acetonitrile and 0.1% formic acid (7:3, v:v). The solution was filtered through a 0.2 μm filter and then analyzed by LC-MS / MS. The enrichment effect of Fe3O4@SiO2@Tb-PDAN on 16 macrolide antibiotics was evaluated by calculating the recovery rate. The recovery rate ranged from 70.16% to 95.53%, and the specific results are shown in Table 2.

[0064]

[0065] Example 3

[0066] (1) Preparation of magnetic Fe3O4 nanoparticles: 1.6g FeCl3·6H2O was accurately weighed into 60mL ethylene glycol and dissolved by stirring with a magnetic stirrer. 2.4g PEG-4000 and 7.4g CH3COONa·3H2O were added to the solution and stirred for 30min to obtain a brown turbid solution. The solution was transferred to a reaction vessel and reacted at 200℃ for 9h. The product was cleaned with anhydrous ethanol to obtain Fe3O4 nanoparticles, which were then vacuum dried at 60℃ for 2h.

[0067] (2) Preparation of Fe3O4@SiO2: Add 0.1g of Fe3O4 nanoparticles from step (1) to 90mL of ethanol solution, disperse by ultrasonication for 30min, then add 1.7mL of ammonia and 1.2mL of tetraethyl orthosilicate, and hydrolyze to obtain Fe3O4@SiO2 particles. The volume ratio of anhydrous ethanol to water in the ethanol solution is 6:1, and the hydrolysis reaction is carried out under the condition of heating and stirring at 32℃ for 20h.

[0068] (3) Preparation of the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN: 120 mg of Fe3O4@SiO2 particles were first added to a round-bottom flask containing 20 mL of tetrahydrofuran. After sonication for 5 min, 39 mg of trimesin (0.24 mmol), 75 mg of terephthalonitrile (0.48 mmol), and 2.5 mL of DBU solution (water as solvent, DBU concentration in solution was 7 mol / L) were added to the round-bottom flask sequentially. The reaction mixture was heated to reflux temperature for 22 h. The obtained product was washed with anhydrous ethanol and ultrapure water until the supernatant became clear. It was then vacuum dried at 60 °C for 4 h to obtain Fe3O4@SiO2@Tb-PDAN. The microscopic characterization results of the obtained material showed that it was similar to the material obtained in Example 1.

[0069] The Fe3O4@SiO2@Tb-PDAN synthesized in this embodiment was used as an adsorbent to extract macrolide antibiotics from water samples.

[0070] Weigh 12 mg of Fe3O4@SiO2@Tb-PDAN and add it to 10 mL of a water sample with pH 9 containing 16 macrolide antibiotics (see Table 3 below, each antibiotic concentration is 2 ng / mL). Vortex for 10 min, and use an external magnetic field to cause Fe3O4@SiO2@Tb-PDAN to settle. Remove the supernatant under the action of the magnetic field, then wash the Fe3O4@SiO2@Tb-PDAN. Add 6 mL of ammonia-acetonitrile solution to the collected Fe3O4@SiO2@Tb-PDAN solution. The volume percentage of ammonia in the ammonia-acetonitrile solution is 1.6%. Vortex for 3 minutes. Under an external magnetic field, the entire ammonia-acetonitrile solution was transferred to another centrifuge tube. 6 mL of ammonia-acetonitrile solution was added to Fe3O4@SiO2@Tb-PDAN, and the mixture was vortexed for 3 min. The ammonia-acetonitrile solution was then removed under an external magnetic field. The eluent from both washes was combined and vortexed to mix. 6 mL of the eluent was dried under nitrogen and reconstituted with 1 mL of a mixture of acetonitrile and 0.1% formic acid (7:3, v:v). The solution was filtered through a 0.2 μm filter and then injected into LC-MS / MS for analysis. The enrichment effect of Fe3O4@SiO2@Tb-PDAN on 16 macrolide antibiotics was evaluated by calculating the recovery rate. The recovery rate ranged from 70.22% to 96.47%, and the specific results are shown in Table 3.

[0071]

[0072]

[0073] Example 4

[0074] The reusability of the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN in Example 1 was tested. Fe3O4@SiO2@Tb-PDAN was used to enrich and extract 16 macrolide antibiotics from a water sample, followed by recovery and reuse. The specific application method is as follows:

[0075] Weigh 12 mg of the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN from Example 1 and add it to 10 mL of a water sample with pH 8 containing 16 macrolide antibiotics (each antibiotic concentration is 2 ng / mL). Vortex for 5 min, and use an external magnetic field to cause Fe3O4@SiO2@Tb-PDAN to precipitate. Remove the supernatant under the action of the magnetic field. Add 6 mL of ammonia-acetonitrile solution to Fe3O4@SiO2@Tb-PDAN, with ammonia accounting for 1.2% of the total volume. Vortex for 5 min, and then transfer the entire ammonia-acetonitrile solution to another centrifuge tube under an external magnetic field. Add another 6 mL of the same ammonia-acetonitrile solution to Fe3O4@SiO2@Tb-PDAN, vortex for 5 min, and then remove the ammonia-acetonitrile solution under an external magnetic field. Combine the eluents from both washes and vortex to mix. Take 6 mL of the eluent and blow it dry with nitrogen. Redissolve the eluent in 1 mL of a mixture of acetonitrile and 0.1% formic acid (7:3, v:v). Filter through a 0.2 μm filter membrane and inject for analysis of 16 macrolide antibiotics. Recover Fe3O4@SiO2@Tb-PDAN, wash and dry it with the same ammonia-acetonitrile solution, and repeat the above steps for adsorption experiments. Calculate the recovery rate.

[0076] The results are as follows Figure 5 As shown, the enrichment and extraction efficiency of the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN of the present invention for macrolide antibiotics in water samples decreases slowly with the increase of repeated use. After three repeated uses, the extraction efficiency for 16 macrolide antibiotics is still between 68.05% and 90.74%, indicating that the adsorbent material has good stability and repeatability.

[0077] Comparative Example 1

[0078] A carbon-nitrogen double bond material was prepared using 1,3,5-TRIS (3'-aldehyde-4'-hydroxybenzene)benzene and ethylenediamine monohydrate as raw materials, 1,4-dioxane as solvent, and acetic acid as catalyst. The specific preparation method is as follows:

[0079] 1,3,5-TRIS (3'-aldehyde-4'-hydroxybenzene) benzene (0.26 g, 0.60 mmol) and ethylenediamine monohydrate (73.2 μL, 0.90 mmol) were thoroughly mixed in 40 mL of 1,4-dioxane solvent, and then 5 mL of acetic acid aqueous solution (12 mol / L) was added. The mixture was transferred to an oil bath and reacted at 70 °C with stirring for 24 h. The product was centrifuged, washed once with 40 mL of 1,4-dioxane, and three times with 30 mL of anhydrous ethanol. Then, it was vacuum dried at 60 °C for 5 h to obtain carbon-nitrogen double bond material.

[0080] The macrolide antibiotics were tested using the materials from Comparative Example 1 (the test experiment was the same as in Example 1), and the results are shown in Table 4 below.

[0081]

[0082]

[0083] As shown in Table 4, the material in Comparative Example 1 showed good extraction efficiency for tilmicosin, avermectin, and moxicillin, with recoveries of 89.13%, 96.89%, and 96.06%, respectively. However, its extraction efficiency for acetomycin, epromycin, doramectin, and emamectin was relatively low, with recoveries of 62.59%, 60.76%, 56.47%, and 61.67%, respectively. The extraction efficiency for the remaining nine macrolide antibiotics was poor, with recoveries ranging from 18.42% to 43.22%. This indicates that the material in Comparative Example 1 only showed good extraction efficiency for three macrolide antibiotics, and the number of macrolide antibiotics that could be efficiently enriched and extracted was limited. In contrast, the material of this invention achieved recoveries of over 70% for all 16 macrolide antibiotics, facilitating the simultaneous and effective extraction of multiple macrolide antibiotics from water and demonstrating significant advantages in the simultaneous high-throughput rapid detection of macrolide antibiotics.

[0084] Comparative Example 2

[0085] A carbon-nitrogen double-bond material was synthesized using Fe3O4@SiO2, 3,3',5,5'-tetraaldehyde biphenyl and p-phenylenediamine as raw materials, dimethyl sulfoxide (DMSO) and 1,4-dioxane as solvents, and acetic acid as a catalyst. The specific preparation method is as follows:

[0086] (1) Dissolve 1.6g FeCl3·6H2O in 60mL ethylene glycol, then add 2.0g PEG-4000 and 7.2g CH3COONa·3H2O and stir thoroughly until homogeneous. React at 200℃ for 8h. After washing the product with anhydrous ethanol, dry it under vacuum at 60℃ to obtain spherical magnetic Fe3O4 nanoparticles for use.

[0087] (2) Add 200 mg of magnetic Fe3O4 nanoparticles to 200 mL of ethanol solution (160 mL of anhydrous ethanol and 40 mL of water, respectively), disperse evenly by ultrasonication, and then add 3 mL of ammonia and 2 mL of tetraethyl orthosilicate. Fe3O4@SiO2 particles are obtained by hydrolysis reaction.

[0088] (3) 150 mg of Fe3O4@SiO2 magnetic particles were added to a round-bottom flask containing 35 mL of 1,4-dioxane. After sonication for 5 min, the flask was placed in an oil bath and stirred. Then, 80.00 mg (0.30 mmol) of 3,3',5,5'-tetraaldehyde biphenyl was dissolved in 10 mL of DMSO, sonicated for 2 min, and then added dropwise to the flask. Next, 64.88 mg (0.60 mmol) of p-phenylenediamine was dissolved in 5 mL of 1,4-dioxane solvent, sonicated for 1 min, and then added dropwise to the flask. Finally, 5 mL of 12 mol / L acetic acid aqueous solution was added dropwise to the mixture, and the reaction was carried out at 70 °C for 24 h. After magnetic separation, the product was washed successively with anhydrous ethanol and ultrapure water until the supernatant became clear, and then vacuum dried at 60 °C for 3 h to obtain the magnetic material.

[0089] The materials used in Comparative Example 2 were used to test macrolide antibiotics (the test experiment was the same as in Example 1), and the results are shown in Table 5 below.

[0090]

[0091]

[0092] As shown in Table 5, the recovery rates of ephemeralin and emamectin in the material of Comparative Example 2 were 43.60% and 52.43%, respectively, while the recovery rates of the remaining 14 macrolide antibiotics were all below 30%. This indicates that the material of Comparative Example 2 is not suitable for the extraction and detection of macrolide antibiotics.

[0093] In summary, this invention constructs a magnetic adsorption material for the enrichment and extraction of macrolide antibiotics in water by encapsulating magnetic Fe3O4 nanoparticles in a shell material formed by the reaction of trimesin and terephthalonitrile. Utilizing the large electron cloud density of the carbon-carbon double bonds and cyano groups in the shell material, various interactions are formed with the target compounds, enabling rapid separation and analysis of multiple macrolide antibiotics in water samples.

Claims

1. A magnetic organic polymer for the enrichment extraction of macrolide antibiotics, characterized by: The magnetic organic polymer is in a core-shell structure, the core is a magnetic Fe3O4 nanoparticle, and the shell is a Tb-PDAN organic polymer formed by the reaction of trimesoyl chloride and p-phenylenediacetonitrile, the Tb-PDAN organic polymer contains both -CN and C=C groups, and the -CN and C=C are connected.

2. The magnetic organic polymer for the enrichment extraction of macrolide antibiotics according to claim 1, characterized by: The magnetic organic polymer is formed by first wrapping the core Fe3O4 nanoparticle with SiO2 to form Fe3O4@SiO2 particles, and then wrapping the Fe3O4@SiO2 particles with the shell material Tb-PDAN organic polymer.

3. The magnetic organic polymer for the enrichment extraction of macrolide antibiotics according to claim 2, characterized by: The magnetic organic polymer is prepared by placing Fe3O4@SiO2 particles, trimesoyl chloride, p-phenylenediacetonitrile and 1,8-diazabicyclo[5.4.0]undec-7-ene in a tetrahydrofuran solvent, and then performing ultrasonic mixing and reflux reaction.

4. The magnetic organic polymer for the enrichment extraction of macrolide antibiotics according to claim 1, characterized by: The magnetic organic polymer can simultaneously extract 16 kinds of macrolide antibiotics.

5. The method for preparing a magnetic organic polymer for the enrichment extraction of a macrolide antibiotic according to any one of claims 1 to 4, characterized in that, The method comprises the following steps: (1) obtaining spherical magnetic Fe3O4 nanoparticles, washing, vacuum drying and then waiting for use; (2) coating SiO2 on the surface of the magnetic Fe3O4 nanoparticles to obtain Fe3O4@SiO2 particles; (3) placing Fe3O4@SiO2 particles, trimesoyl chloride, p-phenylenediacetonitrile and 1,8-diazabicyclo[5.4.0]undec-7-ene in a tetrahydrofuran solvent, ultrasonic mixing, and fully reacting the mixed solution at a reflux temperature, and then washing and drying the product after magnetic separation to obtain the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN.

6. The method for preparing a magnetic organic polymer for the enrichment extraction of macrolide antibiotics according to claim 5, characterized in that, Step (1) adopts a solvothermal method to prepare spherical magnetic Fe3O4 nanoparticles, and specifically comprises the following steps: dissolving FeCl3·6H2O in ethylene glycol, adding PEG-4000 and CH3COONa·3H2O, fully stirring and mixing, and then reacting at 200±5°C for 7-9 hours, and then washing the product with anhydrous ethanol and vacuum drying at 60±5°C to obtain the spherical magnetic Fe3O4 nanoparticles to be used; the mass ratio of FeCl3·6H2O, PEG-4000 and CH3COONa·3H2O is 1.6: (1.8-2.4): (7.0-7.4).

7. The method for preparing a magnetic organic polymer for the enrichment extraction of macrolide antibiotics according to claim 5, characterized by, Step (2) adopts a tetraethyl orthosilicate hydrolysis method to coat SiO2 on the surface of the magnetic Fe3O4 nanoparticles, and specifically comprises the following steps: adding the magnetic Fe3O4 nanoparticles to an ethanol solution, ultrasonic dispersion, then adding ammonia and tetraethyl orthosilicate, and then performing hydrolysis reaction to obtain Fe3O4@SiO2 particles; the dosage ratio of the magnetic Fe3O4 nanoparticles, the ethanol solution, ammonia and tetraethyl orthosilicate is 0.1 g: (90-110) mL: (1.2-1.7) mL: (0.8-1.2) mL; the volume ratio of anhydrous ethanol to water in the ethanol solution is (3-6):1; and the hydrolysis reaction conditions are heating and stirring at 25-32°C for 20-26 hours.

8. The method for preparing the magnetic organic polymer for macrolide antibiotic enrichment and extraction according to claim 7. In step (3), 1,8-diazabicyclo[5.4.0]undec-7-ene is first dissolved in water to form a solution with a molar concentration of 5-7 mol / L, and then added to the tetrahydrofuran solvent; the ratio between the use amounts of the Fe3O4@SiO2 particles, triformylphenyl, p-phenylenediacetonitrile and 1,8-diazabicyclo[5.4.0]undec-7-ene solution is (85-120) mg:(0.24-0.32) mmol:0.48 mmol:(2-3) mL; After the product is separated by magnetism, it is washed with anhydrous ethanol and ultrapure water in sequence, and then vacuum dried at 60±5℃ for 2-4h to obtain the magnetic organic polymer Fe3O4@SiO2@Tb-PDAN.

9. The method of using the magnetic organic polymer for the enrichment extraction of macrolide antibiotics according to any one of claims 1 to 4, characterized in that: The magnetic organic polymer is used as an adsorbent to enrich and extract macrolide antibiotics in water.

10. The method of using the magnetic organic polymer for the enrichment extraction of macrolide antibiotics according to claim 9, characterized in that, Specifically includes the following steps: The magnetic organic polymer is added to the water sample containing macrolide antibiotics, and after extraction by fully mixing, the organic polymer is settled by using an external magnetic field, and the supernatant is removed under the action of the magnetic field. Finally, an eluent is added to the collected organic polymer to recover the analyte for qualitative and / or quantitative determination; the eluent is an ammonia-acetonitrile solution, and the volume ratio of ammonia in the ammonia-acetonitrile solution is 1-2%.

Images