Solid phase extraction material, its manufacturing method and application

Abstract

The present invention relates to a solid-phase extraction material and its manufacturing method and application, which belongs to the field of solid-phase extraction. The method involves pre-polymerizing monomers N-vinylpyrrolidone and divinylbenzene in the presence of a chain transfer agent, then dropping them into an emulsion of monodisperse seed microspheres, and then swelling and reacting them to produce white spheres, and then obtaining a solid-phase extraction material from the white spheres through a reaction in which functional groups are introduced. The solid-phase extraction material obtained by the reaction has a good spherical shape, a large specific surface area, and a high ion exchange capacity. In the process of separating and concentrating PPCPs, the prepared solid-phase extraction material has a synergistic effect on various forces acting on the substance, resulting in high extraction efficiency. By adjusting the pH of the eluent during elution, the degree of ionization of the substance or extraction material can be controlled, and the substance can be selectively separated. Extraction experiment results show that the extraction recovery rate of the substance by the prepared solid-phase extraction material is basically maintained at 85% to 105%, and it can selectively separate acidic, alkaline, neutral, and amphoteric substances.

Description

[Technical Field]

[0001] The present invention is in the field of solid phase extraction, and specifically relates to the preparation and application of a series of uniform particle size reinforced solid phase extraction materials. [Background technology]

[0002] The performance of solid-phase extraction packing materials plays a key role in determining extraction efficiency. The functional groups contained in solid-phase extraction packing materials enable compound concentration through their binding force. Solid-phase extraction packing materials can be divided into molecular polymer matrix, bonded silica gel, inorganic metal oxide, and other reinforced solid-phase extraction packing materials. Reinforced solid-phase extraction packing materials, among others, have a wider range of applications than single-functional solid-phase extraction columns due to their diverse functional groups that enable compound extraction through various binding forces. Reinforced adsorbents have a hybrid retention pattern, extracting analytes through ion interactions while effectively retaining uncharged substances through hydrophobic-hydrophilic interactions. These substances, which have very different physical and chemical properties, can be eluted with different eluents prior to chromatographic analysis. Reinforced ion-exchange polymers can be divided into reinforced cation-exchange adsorbents and reinforced anion-exchange adsorbents according to the ionic groups they bind, and further divided into strong ion-exchange adsorbents and weak ion-exchange adsorbents according to the strength of the binding groups.

[0003] Waters' HLB solid-phase extraction cartridges, with their hydrophilic and hydrophobic backbones, are widely used for the concentration and separation of trace organic compounds in water. However, they suffer from low extraction recovery rates for many organic compounds, especially charged compounds in aqueous solutions. For this reason, Waters has launched a series of supplementary products, including MCX, MAX, WCX, and WAX, which feature a hydrophilic and hydrophobic N-vinylpyrrolidone-divinylbenzene backbone and sulfonic acid, quaternary amine, carboxylic acid, and piperazinyl groups, respectively, and exhibit excellent extraction efficiency for negatively and positively charged organic compounds in water. However, the manufacturing processes for these products are not disclosed.

[0004] Seeded swelling polymerization is an important method for effectively combining hydrophilic and hydrophobic backbones, and can also ensure the monodispersity of the microspheres produced, effectively ensuring the uniformity of particle size of the filler. However, currently, seeded polymerization still presents certain problems in the production of hydrophilic and lipophilic materials. For example, as described in the patent document CN 102382227A, seeded swelling polymerization produces monodisperse microspheres of N-vinylpyrrolidone and divinylbenzene with uniform particle size. However, because N-vinylpyrrolidone is highly hydrophilic, the proportion involved in the swelling polymerization reaction cannot be controlled. As a result, most of the resulting polymer microspheres are the self-polymerization of the hydrophobic divinylbenzene. Furthermore, the hydrophilicity of the product cannot be ensured. Therefore, using it as a precursor to produce modified fillers is uneconomical and has poor extractability. Therefore, how to produce MCX, MAX, WCX, and WAX with uniform particle size is currently an important technical challenge that urgently needs to be overcome in the efficient pretreatment of trace organic matter in water. Summary of the Invention [Problem to be solved by the invention]

[0005] The purpose of the present invention is to overcome the drawback of conventional seed swelling polymerization technology, namely, the inability to control the proportion of the hydrophilic monomer N-vinylpyrrolidone involved in the swelling polymerization reaction. By adding a prepolymerization process before the two-stage swelling polymerization, the hydrophilic substance N-vinylpyrrolidone forms prepolymer micelles with the hydrophobic monomer divinylbenzene before participating in the final polymerization, and becomes hydrophobic. Based on the empirical rule that substances with similar chemical structures are highly compatible with each other, it can enter the activator dibutyl phthalate (DBP). Furthermore, the hydrophilic substance N-vinylpyrrolidone fully participates in the final polymerization reaction, thereby achieving sufficient polymerization of the hydrophilic monomers N-vinylpyrrolidone and divinylbenzene, providing a novel polymerization method for amphiphilic resin microspheres.

[0006] Another object of the present invention is to successfully obtain a range of uniform particle size reinforced solid phase extraction materials using the above-mentioned manufacturing method.

[0007] It is yet another object of the present invention to provide an application of the above solid phase extraction material which exhibits excellent detection or selective separation effects for acidic, alkaline, neutral and amphoteric trace pollutants in water. [Means for solving the problem]

[0008] In order to solve the above problems, the technical solutions adopted by the present invention are as follows:

[0009] A method for producing a solid-phase extraction material includes the steps of pre-polymerizing the monomers N-vinylpyrrolidone and divinylbenzene in the presence of a chain transfer agent, then adding them dropwise to an emulsion of monodisperse seed microspheres, allowing them to swell and react to produce white spheres, and then obtaining a solid-phase extraction material from the white spheres through a reaction that introduces functional groups.

[0010] The concept of the present invention for producing solid-phase extraction materials is to first synthesize hydrophilic and lipophilic solid-phase extraction microspheres, i.e., white spheres, and then introduce various groups with ion exchange properties to produce a series of solid-phase extraction packing materials. By modifying the groups in the hydrophilic and lipophilic backbone, the extractability of acidic, alkaline, neutral, and amphoteric substances can be correspondingly improved, making them suitable for the efficient concentration and separation of hydrophilic organic substances.

[0011] In the conventional seed swelling polymerization method, in order to ensure a good sphere formation rate and yield, the two-stage swelling is usually applied only to highly hydrophobic monomers such as styrene and divinylbenzene. This is because the monodisperse seed microspheres first adsorb the activator dibutyl phthalate (DBP) as a hydrophobic core in water, and then utilize the hydrophobicity of DBP to absorb the hydrophobic monomer involved in the two-stage swelling. In this step, the empirical rule that substances with similar chemical structures are highly compatible with each other is mainly utilized, and finally, the two-stage swollen monomer is polymerized around the seed microspheres in the presence of substances such as initiators. This rule of thumb is not applicable to highly hydrophilic substances such as N-vinylpyrrolidone, which dissolves very easily in water and tends to dissolve in the aqueous phase during the swelling process rather than existing as an independent oil phase. Therefore, it is difficult for these substances to be absorbed into activated seed microspheres and participate in nearby polymerization, based on the empirical rule that substances with similar chemical structures are highly compatible with each other. For this reason, prior art techniques generally do not use highly hydrophilic monomers such as N-vinylpyrrolidone to produce hydrophilic solid-phase extraction microspheres by swelling polymerization. In contrast, the present invention adds a prepolymerization process before the two-stage swelling polymerization, and adjusts the hydrophilicity of the prepolymerized product by adjusting the prepolymerization conditions. This allows for sufficient polymerization of the hydrophilic monomer N-vinylpyrrolidone and the hydrophobic monomer, resulting in a hydrophilic-lipophilic solid-phase extraction microsphere precursor (i.e., white spheres) with uniform particle size, high yield, and high hydrophilicity. This can then be further reacted with functional groups to produce solid-phase extraction microspheres with various properties.

[0012] It should be noted that the white spheres refer to hydrophilic and lipophilic solid-phase extraction microsphere precursors obtained by prepolymerizing the monomers N-vinylpyrrolidone and divinylbenzene in the presence of a chain transfer agent, then adding them dropwise to an emulsion of monodisperse seed microspheres, followed by swelling and reaction, and the white spheres have not been treated by a reaction to introduce functional groups.

[0013] Preferably, the static contact angle of the white ball is less than 90°, preferably less than 85°, more preferably less than 80°, and even more preferably less than 75°.

[0014] Preferably, the particle size of the monodisperse seed microspheres is in the range of 1 to 15 μm.

[0015] Preferably, the prepolymerization specifically includes the steps of adding N-vinylpyrrolidone and divinylbenzene as monomers, an emulsifier, a radical initiator, and a chain transfer agent to an aqueous phase, followed by ultrasonically enhancing dispersion to obtain emulsion B, and prepolymerizing emulsion B at a predetermined temperature.

[0016] Preferably, the mass ratio of the monomers N-vinylpyrrolidone and divinylbenzene is (1 to 81):9.

[0017] Preferably, the mass of the emulsifier is 0.1% to 20% of the total mass of the monomers, the mass of the radical initiator is 0.5% to 4% of the total mass of the monomers, and the molar ratio of the radical initiator to the chain transfer agent is 1:(1 to 2.8).

[0018] Preferably, in the prepolymerization process, the mass ratio of the monomers N-vinylpyrrolidone and divinylbenzene is 1:1, the mass of the initiator is 2% of the total mass of the monomers, and the molar ratio of the radical initiator and the chain transfer agent is 1:1.

[0019] Preferably, the prepolymerization temperature of the emulsion B is 45 to 55°C, the prepolymerization time of the emulsion B is 1 to 24 hours, the swelling temperature is 0 to 30°C, and the swelling time is 4 to 48 hours.

[0020] By using a RAFT chain transfer agent to control the hydrophilic and hydrophobic monomers so that they polymerize regularly, and by adjusting the ratio of hydrophilic and hydrophobic monomers and controlling the prepolymerization reaction conditions such as the amount of RAFT chain transfer agent added and the temperature and time of prepolymerization, the formed amphiphilic micelles swell and enter the vicinity of the seed microspheres to participate in the polymerization, and further produce precursor white spheres for solid-phase extraction microspheres with uniform particle size.

[0021] Preferably, the manufacturing method specifically comprises: a monodisperse seed microsphere preparation step S1, in which styrene and divinylbenzene are mixed in a predetermined ratio to form an oil phase, ethanol and water are mixed to form an aqueous phase, a dispersant and a radical initiator are added to the aqueous phase, and monodisperse seed microspheres are prepared by dispersion polymerization; the monodisperse seed microspheres are added to the aqueous phase in which the dispersant and emulsifier have been dissolved, and a swelling agent and a porogen are also added; and emulsion A is obtained by ultrasonically enhancing dispersion; a white sphere production step S2 in which N-vinylpyrrolidone and divinylbenzene monomers, an emulsifier, a radical initiator, and a chain transfer agent are added to an aqueous phase, followed by ultrasonic dispersion to obtain emulsion B; emulsion B is pre-polymerized at a predetermined temperature, and then added dropwise to emulsion A of monodisperse seed microspheres; the emulsion B is allowed to swell at a low temperature, and then the temperature is gradually raised to allow the mixture to react sufficiently, after which the mixture is discharged, washed, and dried to obtain white spheres; and a solid-phase extraction material production step S3 of obtaining a solid-phase extraction material from the white spheres by a reaction to introduce a functional group.

[0022] Preferably, in step S1, the stirring rotation speed of the dispersion polymerization reaction is 100 to 1000 rpm, the temperature is increased at a rate of 1 to 10°C / 10 minutes, and the reaction time is 4 to 12 hours; Preferably, in step S2, emulsion B is pre-polymerized at a predetermined temperature, and then added dropwise to emulsion A of the monodisperse seed microspheres, and the emulsion B is swollen at a low temperature, and then the temperature is gradually increased, the reaction speed is 100-800 rpm, the temperature is increased by 1-10°C / 30 minutes, and the reaction time is 4-48 hours; Preferably, the radical initiator in step S1 or S2 is one or more of azobisisobutyronitrile, azobisisoheptonitrile, dimethyl azobisisobutyrate, azobisisobutylamidine hydrochloride, azobisisobutylimidazoline hydrochloride, dibenzoyl peroxide, benzoyl peroxide, and the emulsifier in step S1 or S2 is one or more of anionic emulsifiers: sodium dodecyl sulfate, sodium dodecylbenzenesulfonate, fatty acid soap, and / or the dispersant in step S1 is one or more of polyethylene glycol, sodium hexametaphosphate, polyethylene glycol fatty acid ester, and polyvinylpyrrolidone, and the porogen is one or more of toluene, xylene, ethyl acetate, acetonitrile, tetrahydrofuran, acetone, and normal hexane; More preferably, the dispersant used in step S1 is polyvinylpyrrolidone, the emulsifier is sodium dodecyl sulfate, the initiator is azobisisobutyronitrile, and the porogen is toluene; and / or The swelling agent in step S1 is one or more of benzene, toluene, xylene, dichloroethane, trichloromethane, dimethyl phthalate, diethyl phthalate, and dibutyl phthalate; In step S1, the mass ratio of water to ethanol in the aqueous phase is 15:85 to 85:15, preferably 40:60 to 60:40, and more preferably 50:50, and the mass ratio of the oil phase to the aqueous phase is 25:75 to 75:25, and preferably 25:75; and / or The proportion of the dispersant added in step S1 is 2% to 10% of the mass of the monomer, preferably 2% to 5%, more preferably 4%, and / or The addition ratio of the initiator in step S1 is 0.5 to 4% of the mass of the monomer, preferably 0.5 to 2%, more preferably 1%; and / or The temperature of the dispersion polymerization reaction in step S1 is controlled to 60 to 95°C, and / or The mass ratio of the monodisperse seed microspheres to the swelling agent in step S1 is 1:2 to 1:10; and / or The mass ratio of the swelling agent to the porogen in step S1 is 1:1; and / or the mass of the monodisperse seed microspheres in emulsion A in step S1 is 1% to 5% of the total mass of the aqueous phase; and / or In step S1, the monodisperse seed microspheres are added to an aqueous phase containing a dispersant and an emulsifier, and the mass of the dispersant and the emulsifier is 0.2%-25% and 0.1%-20% of the mass of the monodisperse seed microspheres, respectively; and / or The chain transfer agent in step S2 is one or more of 2-[dodecylthio(thiocarbonyl)thio]-2-methylpropionic acid, isobutyronitrile dithiobenzoate, 2-cyanopropan-2-ylbenzodithioate, 2-cyanopropan-2-ylbenzodithioate, S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate, S,S'-p-(α,α'-dimethyl-α''-acetic acid) trithiocarbonate, and S-1-dodecyl-S'(α,α'-dimethyl-α''-acetic acid) trithiocarbonate. More preferred are S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate, S,S'-p-(α,α'-dimethyl-α''-acetic acid) trithiocarbonate, and S-1-dodecyl-S'(α,α'-dimethyl-α''-acetic acid) trithiocarbonate.

[0023] Preferably, the reaction introducing the functional group in step S3 includes a reaction using an aminating reagent to produce a strong cation or weak cation exchange solid-phase extraction material having amine groups, a reaction using an oxidizing reagent to produce a weak anion exchange solid-phase extraction material having carboxyl groups, or a reaction using a sulfonating reagent to produce a strong anion exchange solid-phase extraction material having sulfonic acid groups.

[0024] Preferably, the reaction for producing a strong or weak cation exchange solid-phase extraction material having an amine group may be a reaction in which chlorine spheres having a chloromethyl group active group are first produced using a chloromethylation reagent, and then the chlorine spheres are reacted with an amination reagent to produce a strong or weak cation exchange solid-phase extraction material having an amine group.

[0025] Preferably, the reaction for producing the weak anion exchange solid-phase extraction material having a carboxyl group described above may be a reaction in which chlorine spheres having a chloromethyl group active group are first produced using a chloromethylation reagent, and then a weak anion exchange solid-phase extraction material having a carboxyl group is produced using an oxidation reagent.

[0026] Preferably, the reaction to produce a strong anion exchange solid phase extraction material having sulfonic acid groups may be a direct reaction between white spheres and a sulfonating reagent.

[0027] In other words, The solid phase extraction material production step S3 includes: Using the white spheres as raw material, introduce chloromethyl group active groups to obtain chlorine spheres, and using the chlorine spheres as raw material, replace the chloromethyl groups with amine groups to obtain a strong cation or weak cation exchange solid phase extraction material; or Using the white spheres as a raw material, introduce chloromethyl group active groups to obtain chlorine spheres, and then use the chlorine spheres as a raw material to subject the chloromethyl groups to an oxidation reaction to obtain a weak anion exchange solid-phase extraction material; or The method includes using the white spheres as raw material, adding a sulfonation reagent to cause a sulfonation reaction, and obtaining a strong anion exchange solid-phase extraction material. The chloromethylating reagent is one or more of chloromethyl methyl ether, bis(chloromethyl) ether, methoxyacetyl chloride, chloromethyl alkyl ether.

[0028] The aminating reagent is one or more of diethylamine, triethylamine, dimethylamine, trimethylamine, dimethylbutylamine, N-methylimidazole, 1,2-ethylenediamine, and piperazine, and the ratio of the mass of the aminating reagent to the mass of the chlorine atom is 1:1 to 100:1, preferably 1:1 to 10:1.

[0029] The oxidation reagent is one or more of hydrogen peroxide, potassium permanganate, and aluminum oxide, and the ratio of the mass of the oxidation reagent to the mass of the chlorine ball is 0.5:1 to 50:1, preferably 0.5:1 to 20:1.

[0030] The sulfonating reagent is one or more of concentrated sulfuric acid, chlorosulfonic acid, and sulfamic acid, and the ratio of the mass of the sulfonating reagent to the mass of the white spheres is 1:1 to 100:1, preferably 1:1 to 10:1.

[0031] Preferably, in step S3, the rotation speed of the amination reaction is 100 to 800 rpm, the reaction temperature is 40 to 110° C., and the reaction time is 4 to 32 hours.

[0032] Preferably, in step S3, the rotation speed of the oxidation reaction is 100 to 800 rpm, the reaction temperature is 50 to 150° C., and the reaction time is 3 to 24 hours.

[0033] Preferably, in step S3, the rotation speed of the sulfonation reaction is 100 to 800 rpm, the reaction temperature is 80 to 140° C., and the reaction time is 4 to 48 hours.

[0034] The present invention further provides a solid-phase extraction material produced by the above-mentioned method for producing a solid-phase extraction material, which includes a strong cation or weak cation exchange solid-phase extraction material having amine groups, a weak anion exchange solid-phase extraction material having carboxyl groups, or a strong anion exchange solid-phase extraction material having sulfonic acid groups.

[0035] It should be noted that the functional groups vary depending on the type of solid-phase extraction material, and substances with different properties can be selectively extracted. In the case of substances with pKa < 5.0, a weak cation exchange material can be selected; in the case of substances with 2 < pKa < 10, a strong anion exchange material can be selected. An acid solution is added in the washing process, and the elution process is divided into two stages. In the first stage, neutral substances are eluted and separated with an organic solvent, and in the second stage, elution is carried out with an organic solvent mixed with an alkali. In the case of substances with pKa > 9, a weak anion exchange material can be selected; in the case of substances with 2 < pKa < 10, a strong cation exchange material can be selected. An alkali solution is added in the washing process, and the elution process is divided into two stages. In the first stage, neutral substances are eluted and separated with an organic solvent, and in the second stage, elution is carried out with an organic solvent mixed with an acid.

[0036] The acid used in the above washing process is one or more of formic acid, acetic acid, lactic acid, and oxalic acid, and the concentration of the acid is preferably 0.1% - 25%. The organic eluent used in the elution process is one or more of methanol, acetonitrile, and ethyl acetate. The alkali used in the elution process is one or more of ammonia water, dimethylamine, and trimethylamine, and the concentration of the alkali is preferably 0.1% - 25%.

[0037] Preferably, the solid-phase extraction material has an average particle size of 5 - 100 μm, a specific surface area of 300 - 1000 m 2 / g, and an exchange capacity of 0.1 - 5 mmol / g.

[0038] The present invention further provides the application of the above solid-phase extraction material in the extraction and concentration of trace pollutants and charged pollutants in water.

Advantages of the Invention

[0039] Compared with the prior art, the beneficial effects of the present invention are as follows.

[0040] (1) The present invention provides a synthetic method for introducing a hydrophilic monomer into the oil phase to participate in the reaction using a seed swelling method. The concept of using a RAFT chain transfer agent to regularly prepolymerize hydrophilic and hydrophobic monomers to form amphiphilic micelles, which then participate in swelling, is a completely new method in the field, solving the problem of the difficulty of using hydrophilic monomers to produce solid-phase extraction microspheres with uniform particle size using a seed swelling method in the prior art. Furthermore, the uniform particle size white spheres produced by the production method of the present invention can reach a yield of over 80%, have good hydrophilicity, and are highly economically beneficial.

[0041] (2) The static contact angle of the white spheres produced by the present invention is less than 90°, in some embodiments, the static contact angle is less than 85°, in some embodiments, the static contact angle is less than 80°, and in some embodiments, the static contact angle is less than 75°, and they have good hydrophilicity and uniform particle size, making them good precursors for the subsequent solid-phase extraction microsphere production reaction.

[0042] (3) In the process of producing solid-phase extraction microspheres from white spheres by reaction in the present invention, the reactions of chloromethylation, amination, sulfonation, and oxidation are relatively thorough, no by-products are produced, and reproducibility is high. The obtained solid-phase extraction microspheres have a uniform particle size distribution, with a particle size of 30 to 50 μm, and are all spherical. The surface of the microspheres contains many pore structures that contribute to the transfer of substances, and the material has a large specific surface area and a high ion exchange capacity.

[0043] (4) The solid-phase extraction microsphere materials prepared in the present invention have high extraction efficiency of the corresponding substances, high data reproducibility, and high reusability. [Brief explanation of the drawings]

[0044] [Figure 1] 1 shows the synthesis steps in Example 1 of the present invention. [Figure 2] FIG. 1 is a scanning electron microscope image of a white sphere produced in Example 1 of the present invention. [Figure 3] FIG. 2 is a contact angle diagram of a white ball in Example 1 of the present invention. [Figure 4] 1 is a photograph of a white ball product according to Example 1 of the present invention. DETAILED DESCRIPTION OF THE INVENTION

[0045] Unless otherwise defined, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art, and the term "and / or" as used herein includes any and all combinations of one or more of the associated listed items.

[0046] In the examples, unless specific conditions are specified, the experiments are carried out under standard conditions or under conditions recommended by the manufacturer. Reagents or equipment used without a manufacturer's name are all commercially available products.

[0047] As used herein, the term "about" is used to provide flexibility and uncertainty associated with a given term, measurement, or value. One of ordinary skill in the art can readily ascertain the degree of flexibility for a particular variable.

[0048] Concentrations, temperatures, amounts, and other numerical data may be expressed in range format herein. It should be understood that such range format is used merely for convenience and brevity, and should be interpreted flexibly to include not only the numerical values ​​explicitly recited as range limits, but also all individual numerical values ​​or subranges within that range, as if each numerical value and subrange were both explicitly recited. For example, a numerical range of about 1 to about 4.5 should be interpreted as including not only the explicitly recited limit of 1 to about 4.5, but also the individual numerical values ​​(e.g., 2, 3, 4) and subranges (e.g., 1 to 3, 2 to 4, etc.). The same applies to ranges recited with only a single numerical value; for example, "less than about 4.5" should be interpreted as including all recited values ​​and ranges. Furthermore, such interpretation should be applied regardless of the breadth of the range or characteristic being described.

[0049] The static contact angle in the present invention is measured using a DSA100 type contact angle measuring device.

[0050] The present invention will now be further described with reference to specific examples.

[0051] Example 1 (1) Preparation of monodisperse seed microspheres Mix 15 mL of ethanol and 15 mL of water to form the aqueous phase. Add 0.4 g of polyvinylpyrrolidone as a dispersant and 0.1 g of benzoyl peroxide as an initiator to the aqueous phase and stir at 60°C for 30 minutes until completely dissolved. Mix 8 g of styrene and 2 g of divinylbenzene to form the oil phase. Add these dropwise to the aqueous solution and mix uniformly. Then, gradually increase the temperature to 75°C at a rate of 3°C / 10 min. Maintain the stirring speed at 450-500 rpm and react for 4 hours to obtain monodisperse seed microspheres with a particle size of 5-10 μm.

[0052] To 100 mL of aqueous solution, add 0.5 g of polyvinylpyrrolidone as a dispersant, 0.375 g of sodium dodecyl sulfate as an emulsifier, 2 g of the above monodisperse seed microspheres, 10 g of toluene as a porogen, and 10 g of dimethyl phthalate as a swelling agent, and then subject to 200 W ultrasonic enhanced dispersion to obtain emulsion A.

[0053] (2) Manufacturing of uniformly sized white balls The secondary polymerized monomers, 10 g of N-vinylpyrrolidone and 10 g of divinylbenzene, 0.375 g of sodium dodecyl sulfate as an emulsifier, 0.4 g of benzoyl peroxide as an initiator, and 0.46 g of S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate as a RAFT chain transfer agent, were added to the aqueous phase and then subjected to ultrasonic dispersion at 200 W for 1 hour to obtain emulsion B. Emulsion B was prepolymerized at 50°C for 2 hours and then added dropwise to emulsion A. The mixture was then allowed to swell at 30°C for 24 hours, with the stirring speed maintained at 200 rpm. After swelling was complete, the solution was heated to 80°C at 5°C / 30 min intervals and reacted for 24 hours while stirring at 750 rpm. The reacted solution was precipitated, filtered, washed repeatedly with methanol and water, and vacuum-dried for the required time to obtain uniformly sized white spheres.

[0054] The static contact angle of the produced white balls was measured using a DSA100 contact angle measuring device and found to be 73.28°. Elemental analysis revealed that the N content of the white balls was 2.13%, the particle size distribution was 30-50 μm, and the specific surface area was 300-1200 m. 2 / g.

[0055] (3) Fabrication of reinforced solid-phase extraction materials 10 g of the above white spheres are added to 50 mL of chloromethyl methyl ether, and 3.5 g of ferric chloride is added as a catalyst. The mixture is reacted at 50°C under acidic conditions for 12 hours to introduce the active group, chloromethyl, and obtain chlorine spheres.

[0056] A certain amount of chlorine spheres is added to trimethylamine in a mass ratio of 1:3, and the mixture is reacted at 60°C and 300 rpm for 24 hours to obtain a strong cation exchange solid-phase extraction material, MAX.

[0057] A certain amount of chlorine spheres is added to dimethylamine in a mass ratio of 1:3, and the mixture is reacted at 70°C and 300 rpm for 24 hours to obtain a weak anion exchange solid-phase extraction material, WAX.

[0058] A certain amount of white spheres is added to concentrated sulfuric acid in a mass ratio of 1:3, and the mixture is reacted under conditions of 140°C and 300 rpm for 8 hours to obtain a strong anion exchange solid-phase extraction material MCX.

[0059] A certain amount of chlorine spheres is added to hydrogen peroxide in a mass ratio of 1:3, and the mixture is reacted under conditions of 80°C and 300 rpm for 8 hours to obtain a weak cation exchange solid-phase extraction material WCX.

[0060] Example 2 The substances selected were nortriptyline (pKa=9.7), amitriptyline (pKa=9.4), and triclosan (pKa=8.1), which are neutral at pH=7, and ibuprofen (pKa=4.9), bezafibrate (pKa=3.6), and indomethacin (pKa=4.5), which are acidic, and the MAX strong cation exchange solid-phase extraction material prepared in Example 1 was selected.

[0061] (1) Fill 500 mg of solid-phase extraction material into a 6 mL solid-phase extraction column with screen plates on both ends, weigh out an appropriate amount of each of the above drugs, dissolve them in methanol to prepare a 1 g / L standard stock solution, and aspirate an appropriate amount of each standard stock solution to prepare a 1 mg / L mixed standard solution and a 1 mg / L mixed internal standard solution.

[0062] (2) Activate the solid-phase extraction material with 5 mL of methanol, wash the material with 5 mL of water, and then pass it through a solid-phase extraction column. Control the column flow rate at 10 mL / min. After passing through the column, wash the solid-phase extraction column with 5 mL of 5% ammonia water to completely ionize the acidic substances and convert them to an ionized state. Next, elute neutral and alkaline substances with 5 mL of methanol solution. Finally, elute acidic substances with 5 mL of 2% formic acid methanol solution. Blowing each of the above eluents with a nitrogen blower until they are essentially dry, and then add acetonitrile to a constant volume of 1 mL.

[0063] (3) Detection was performed by instrument using ultra-high performance liquid chromatography-tandem mass spectrometry technology, gradient elution was performed using 0.1% (v / v) formic acid aqueous solution and acetonitrile as the mobile phase, multiple reaction monitoring (MRM) was performed in electrospray positive ion mode, and quantification was performed using the internal standard method, with the recovery rates ranging from 92.4% to 103.8%.

[0064] When extraction experiments were carried out using Oasis (registered trademark) MAX sold by Waters, the recovery rates were all 94.0% to 102.9% under the same extraction and detection conditions.

[0065] Example 3 The selected substances were paracetamol (pKa=9.4) and triclosan (pKa=8.14), which are neutral at pH=7, ofloxacin (pKa=5.97, 9.28), which is amphoteric, and clarithromycin (pKa=9.0), erythromycin (pKa=8.9), and ormetoprim (pKa=7.11), which are alkaline, and the strong anion exchange solid-phase extraction material MCX prepared in Example 1 was selected.

[0066] (1) 500 mg of solid-phase extraction material is packed into a 6 mL solid-phase extraction column with screen plates on both ends, and an appropriate amount of each of the above drugs is weighed out and dissolved in methanol to prepare a 1 g / L standard stock solution. An appropriate amount of each standard stock solution is then aspirated to prepare a 1 mg / L mixed standard solution and a 1 mg / L mixed internal standard solution.

[0067] (2) Activate the solid-phase extraction material with 5 mL of methanol, wash the material with 5 mL of water, and then pass it through a solid-phase extraction column. Control the flow rate at 10 mL / min. After passing through the column, wash the solid-phase extraction column with 5 mL of 2% formic acid to completely ionize the alkaline substances and convert them to an ionized state. Next, elute neutral and acidic substances with 5 mL of methanol solution. Finally, elute acidic substances with 5 mL of 5% aqueous ammonia-methanol solution. Spray each of the above eluents with a nitrogen blower until they are essentially dry, and then add acetonitrile to a constant volume of 1 mL.

[0068] (3) Detection was performed by instrument using ultra-high performance liquid chromatography-tandem mass spectrometry technology, gradient elution was performed using 0.1% (v / v) formic acid aqueous solution and acetonitrile as the mobile phase, multiple reaction monitoring (MRM) was performed in electrospray positive ion mode, and quantification was performed using the internal standard method, with the recovery rates ranging from 89.2% to 103.1%.

[0069] When extraction experiments were carried out using Oasis (registered trademark) MCX sold by Waters, the recovery rates were all 84.4% to 98.9% under the same extraction and detection conditions.

[0070] Example 4 Sulfaguanidine (pKa = 2.22, 11.22), a neutral substance at pH 7, and ketoprofen (pKa = 4.5), salicylic acid (pKa = 3.0), and sulfamethoxazole (pKa = 1.6, 5.7), which are acidic substances, were selected as the selected substances, and the WAX ​​of the weak cation exchange solid-phase extraction material prepared in Example 1 was selected.

[0071] (1) 500 mg of solid-phase extraction material is packed into a 6 mL solid-phase extraction column with screen plates on both ends, and an appropriate amount of each of the above drugs is weighed out and dissolved in methanol to prepare a 1 g / L standard stock solution. An appropriate amount of each standard stock solution is then aspirated to prepare a 1 mg / L mixed standard solution and a 1 mg / L mixed internal standard solution.

[0072] (2) Activate the solid-phase extraction material with 5 mL of methanol, wash the material with 5 mL of water, and then pass it through a solid-phase extraction column. The flow rate is controlled at 10 mL / min. After passing through the column, wash the column with 5 mL of 2% formic acid to ionize the groups in the solid-phase extraction material and convert them to an ionized state. Next, elute neutral and alkaline substances with 5 mL of methanol solution. Finally, elute acidic substances with 5 mL of 5% aqueous ammonia-methanol solution. Blowing each of the above eluents with a nitrogen blower until they are essentially dry, the solution is then diluted to 1 mL with acetonitrile.

[0073] (3) Detection was performed by instrument using ultra-high performance liquid chromatography-tandem mass spectrometry technology, gradient elution was performed using 0.1% (v / v) formic acid aqueous solution and acetonitrile as the mobile phase, multiple reaction monitoring (MRM) was performed in electrospray positive ion mode, and quantification was performed using the internal standard method, with the recovery rates ranging from 85.2% to 101.8%.

[0074] When extraction experiments were carried out using Oasis (registered trademark) WAX sold by Waters, the recovery rates were all 86.8% to 100.2% under the same extraction and detection conditions.

[0075] Example 5 The weak anion exchange solid-phase extraction material WCX prepared in Example 1 was selected as the selected substances, which are neutral at pH 7: chloramphenicol (pKa = 11.0), carbamazepine (pKa = 13.94), and florfenicol (pKa = 10.73), and alkaline substances: amitriptyline (pKa = 9.4), atenolol (pKa = 9.6), and salbutamol (pKa = 10.3).

[0076] (1) 500 mg of solid-phase extraction material is packed into a 6 mL solid-phase extraction column with screen plates on both ends, and an appropriate amount of each of the above drugs is weighed out and dissolved in methanol to prepare a 1 g / L standard stock solution. An appropriate amount of each standard stock solution is then aspirated to prepare a 1 mg / L mixed standard solution and a 1 mg / L mixed internal standard solution.

[0077] (2) Activate the solid-phase extraction material with 5 mL of methanol, wash the material with 5 mL of water, and then pass it through a solid-phase extraction column. The flow rate is controlled at 10 mL / min. After passing through the column, wash the column with 5 mL of 5% ammonia water to ionize the groups in the solid-phase extraction material and convert them to an ionized state. Next, elute neutral and acidic substances with 5 mL of methanol solution. Finally, elute alkaline substances with 5 mL of 2% formic acid methanol solution. Blowing each of the above eluents with a nitrogen blower until they are essentially dry, the solution is then diluted to 1 mL with acetonitrile.

[0078] (3) Instrumental detection was performed using ultra-high performance liquid chromatography-tandem mass spectrometry technology, gradient elution was performed using 0.1% (v / v) formic acid aqueous solution and acetonitrile as the mobile phase, multiple reaction monitoring (MRM) was performed in electrospray positive ion mode, and quantification was performed using the internal standard method, with recoveries ranging from 91.9% to 105.2%.

[0079] When extraction experiments were carried out using Oasis (registered trademark) WCX sold by Waters, the recovery rates were all 91.6% to 104.6% under the same extraction and detection conditions.

[0080] Example 6 In this example, white spheres are produced in the same manner as in Example 1, except that the amount of RAFT chain transfer agent S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate added is 0.69 g.

[0081] The white spheres produced by this method have a static contact angle of 79.71°, an N element content of 1.10%, and a particle size distribution of 20-100 μm.

[0082] Example 7 In this example, white spheres are produced in the same manner as in Example 1, except that the amount of RAFT chain transfer agent S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate added is 0.92 g.

[0083] The white spheres produced by this method have a static contact angle of 87.53°, and elemental analysis shows that the N element content is 0.9% and the particle size distribution is 20-100 μm.

[0084] Example 8 In this example, white spheres are produced in the same manner as in Example 1, except that the amount of RAFT chain transfer agent S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate added is 1.15 g.

[0085] The white spheres produced by this method have a static contact angle of 84.41°, an N element content of 1.24%, and a particle size distribution of 20 to 200 μm.

[0086] Example 9 In this example, white spheres are produced in the same manner as in Example 1, except that emulsion B is prepolymerized at 50° C. for 1 hour.

[0087] The white spheres produced by this method have a static contact angle of 89.87°, an N element content of 0.77%, and a particle size distribution of 20 to 200 μm.

[0088] Example 10 In this example, white spheres are produced in the same manner as in Example 1, except that emulsion B is prepolymerized at 50° C. for 3 hours.

[0089] The white spheres produced by this method have a static contact angle of 89.00°, an N element content of 0.49%, and a particle size distribution of 20 to 200 μm.

[0090] Example 11 In this example, white spheres are produced in the same manner as in Example 1, except that the RAFT chain transfer agent is S-1-dodecyl-S'(α,α'-dimethyl-α''-acetic acid) trithiocarbonate (0.46 g).

[0091] The white spheres produced by this method have a static contact angle of 84.00°, an N element content of 1.55%, and a particle size distribution of 20 to 200 μm.

[0092] Example 12 In this example, white spheres are produced in the same manner as in Example 1, except that the RAFT chain transfer agent is S,S'-p-(α,α'-dimethyl-α''-acetic acid) trithiocarbonate (0.46 g).

[0093] The white spheres produced by this method have a static contact angle of 84.89°, an N element content of 0.49%, and a particle size distribution of 20 to 200 μm.

[0094] Comparative Example 1 In this comparative example, white balls are produced in the same manner as in Example 1, except that the RAFT chain transfer agent is cyanomethyl N-methyl-N-phenyldithiocarbamate (0.46 g).

[0095] The white spheres produced by this method had a static contact angle of 96.06°, an N content of 0.22%, and a particle size distribution of 1-200 μm. Because the contact angle was greater than 90°, making it a hydrophobic contact angle, and the N content was extremely low, it was determined that most of the obtained polymer microspheres were the result of self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone was not sufficiently involved in the polymerization, resulting in a failed reaction.

[0096] Comparative Example 2 In this comparative example, white spheres are produced in the same manner as in Example 1, except that the prepolymerization temperature of emulsion B is 40°C.

[0097] The white spheres produced by this method had a static contact angle of 108.33°, an N element content of 0, and a particle size distribution of 1 to 200 μm. Because the contact angle was greater than 90°, making it a hydrophobic contact angle, and the N element content was 0, it was determined that most of the obtained polymer microspheres were the result of self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone was not involved in the polymerization, resulting in a failed reaction.

[0098] Comparative Example 3 In this comparative example, white spheres are produced in the same manner as in Example 1, except that the prepolymerization temperature of emulsion B is 60°C.

[0099] The white spheres produced by this method had a static contact angle of 107.08°, an N element content of 0, and a particle size distribution of 1 to 200 μm. Because the contact angle was greater than 90°, making it a hydrophobic contact angle, and the N element content was 0, it was determined that most of the obtained polymer microspheres were the result of self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone was not involved in the polymerization, resulting in a failed reaction.

[0100] Comparative Example 4 In this comparative example, white spheres are produced in the same manner as in Example 1, except that the amount of RAFT chain transfer agent S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate added is 0.23 g.

[0101] The white spheres produced by this method had a static contact angle of 99.52°, an N content of 0.47%, and a particle size distribution of 1-200 μm. Because the contact angle was greater than 90°, making them hydrophobic, and the N content was extremely low, it was determined that most of the obtained polymer microspheres were the result of self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone was not sufficiently involved in the polymerization, resulting in a failed reaction.

[0102] Comparative Example 5 (1) Preparation of monodisperse seed microspheres Mix 15 mL of ethanol and 15 mL of water to form the aqueous phase. Add 0.4 g of polyvinylpyrrolidone as a dispersant and 0.1 g of benzoyl peroxide as an initiator to the aqueous phase and stir at 60°C for 30 minutes until completely dissolved. Mix 8 g of styrene and 2 g of divinylbenzene to form the oil phase. Add these dropwise to the aqueous solution and mix uniformly. Then, gradually increase the temperature to 75°C at a rate of 3°C / 10 min. Maintain the stirring speed at 450-500 rpm and react for 4 hours to obtain monodisperse seed microspheres with a particle size of 5-10 μm.

[0103] To 100 mL of aqueous solution, add 0.5 g of polyvinylpyrrolidone as a dispersant, 0.375 g of sodium dodecyl sulfate as an emulsifier, 2 g of the above monodisperse seed microspheres, 10 g of toluene as a porogen, and 10 g of dimethyl phthalate as a swelling agent, and then subject to 200 W ultrasonic enhanced dispersion to obtain emulsion A.

[0104] (2) Manufacturing of uniformly sized white balls The aqueous phase was mixed with 10g of N-vinylpyrrolidone and 10g of divinylbenzene (secondary polymerized monomers), 0.375g of sodium dodecyl sulfate as an emulsifier, and 0.4g of benzoyl peroxide as an initiator. This was then ultrasonically dispersed at 200W for 1 hour to obtain Emulsion B. Emulsion B was then added dropwise to Emulsion A while maintaining a stirring speed of 200 rpm. After swelling was complete, the solution was heated to 80°C at a rate of 5°C / 30 minutes and reacted for 24 hours while stirring at 750 rpm. The reacted solution was precipitated, filtered, washed repeatedly with methanol and water, and then vacuum dried for a certain period of time to obtain uniformly sized white spheres.

[0105] The white spheres produced by this method (without prepolymerization) had a static contact angle of 100.97°, a zero N element content, and a particle size distribution of 1-200 μm. Because the contact angle was greater than 90°, indicating a hydrophobic contact angle, and the N element content was zero, most of the obtained polymer microspheres were determined to be the result of self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone was not involved in the polymerization, resulting in a failed reaction. The above content is merely an illustrative description of the present invention and its embodiments, and is not intended to be limiting. The examples are merely one embodiment of the present invention, and actual embodiments are not limited thereto. Therefore, any embodiments and examples similar to the technical solution designed by those skilled in the art based on the suggestions and without departing from the spirit and scope of the present invention and requiring no creative effort are also within the scope of protection of the present invention.

Claims

1. The method includes the steps of pre-polymerizing monomers N-vinylpyrrolidone and divinylbenzene in the presence of a chain transfer agent, then adding them dropwise to an emulsion of monodisperse seed microspheres, allowing them to swell and react to produce white spheres, and then obtaining a solid-phase extraction material from the white spheres through a reaction introducing functional groups; The prepolymerization includes the steps of: adding N-vinylpyrrolidone and divinylbenzene, which are monomers, an emulsifier, a radical initiator, and a chain transfer agent to an aqueous phase, and then performing ultrasonic dispersion to obtain emulsion B; and prepolymerizing emulsion B at a predetermined temperature. The prepolymerization temperature of the emulsion B is 45 to 55°C, and the prepolymerization time of the emulsion B is 1 to 24 hours. The method for producing a solid-phase extraction material is characterized in that the reaction introducing the functional group includes a reaction using an aminating reagent to produce a strong cation or weak cation exchange solid-phase extraction material having an amine group, a reaction using an oxidizing reagent to produce a weak anion exchange solid-phase extraction material having a carboxyl group, or a reaction using a sulfonating reagent to produce a strong anion exchange solid-phase extraction material having a sulfonic acid group.

2. The method for producing a solid-phase extraction material according to claim 1, wherein the mass ratio of the monomers N-vinylpyrrolidone and divinylbenzene is (1-81):

9.

3. The method for producing a solid-phase extraction material according to claim 1, characterized in that the mass of the emulsifier is 0.1-20% of the total mass of the monomers, the mass of the radical initiator is 0.5%-4% of the total mass of the monomers, and the molar ratio of the radical initiator to the chain transfer agent is 1:(1-2.8).

4. 2. The method for producing a solid-phase extraction material according to claim 1, wherein the swelling temperature is 0 to 30° C. and the swelling time is 4 to 48 hours.

5. a monodisperse seed microsphere preparation step S1, which comprises mixing styrene and divinylbenzene in a predetermined ratio to form an oil phase, mixing ethanol and water to form an aqueous phase, adding a dispersant and a radical initiator to the aqueous phase, and preparing monodisperse seed microspheres through a dispersion polymerization reaction; adding the monodisperse seed microspheres to the aqueous phase containing the dispersant and emulsifier dissolved therein, adding a swelling agent and a porogen, and then performing ultrasonically enhanced dispersion to obtain emulsion A; a white sphere production step S2 in which N-vinylpyrrolidone and divinylbenzene monomers, an emulsifier, a radical initiator, and a chain transfer agent are added to an aqueous phase, followed by ultrasonic dispersion to obtain emulsion B; emulsion B is pre-polymerized at a predetermined temperature, and then added dropwise to emulsion A of monodisperse seed microspheres, which are allowed to swell at a low temperature and then gradually heated to a high temperature; the resulting mixture is then sufficiently reacted, discharged, washed, and dried to obtain white spheres; 2. The method for producing a solid-phase extraction material according to claim 1, further comprising a step S3 of producing a solid-phase extraction material from the white spheres by a reaction introducing a functional group.

6. the radical initiator in step S1 or S2 is one or more of azobisisobutyronitrile, azobisisoheptonitrile, dimethyl azobisisobutyrate, azobisisobutylamidine hydrochloride, azobisisobutylimidazoline hydrochloride, dibenzoyl peroxide, benzoyl peroxide; and / or The emulsifier in step S1 or S2 is one or more of anionic emulsifiers: sodium dodecyl sulfate, sodium dodecylbenzene sulfonate, and fatty acid soap; and / or the dispersant in step S1 is one or more of polyethylene glycol, sodium hexametaphosphate, polyethylene glycol fatty acid ester, and polyvinylpyrrolidone, and the porogen is one or more of toluene, xylene, ethyl acetate, acetonitrile, tetrahydrofuran, acetone, and normal hexane; and / or the swelling agent in step S1 is one or more of benzene, toluene, xylene, dichloroethane, trichloromethane, dimethyl phthalate, diethyl phthalate, and dibutyl phthalate; and / or the mass ratio of water to ethanol in the aqueous phase in step S1 is (15:85) to (85:15), and the mass ratio of the oil phase to the aqueous phase is (25:75) to (75:25); and / or The dispersant content in step S1 is 2% to 10% of the mass of the monomer; and / or The addition ratio of the initiator in step S1 is 0.5% to 4% of the mass of the monomer, and / or The temperature of the dispersion polymerization reaction in step S1 is controlled to 60 to 95°C, and / or The mass ratio of the monodisperse seed microspheres to the swelling agent in step S1 is between (1:2) and (1:10); and / or The mass ratio of the swelling agent to the porogen in step S1 is 1:1; and / or the mass of the monodisperse seed microspheres in emulsion A in step S1 is 1% to 5% of the total mass of the aqueous phase; and / or In step S1, the monodisperse seed microspheres are added to an aqueous phase containing a dispersant and an emulsifier dissolved therein, and the mass of the dispersant and the emulsifier is 0.2% to 25% and 0.1% to 20% of the mass of the monodisperse seed microspheres, respectively; and / or 6. The method for producing a solid-phase extraction material according to claim 5, wherein the chain transfer agent in step S2 is one or more of 2-[dodecylthio(thiocarbonyl)thio]-2-methylpropionic acid, isobutyronitrile dithiobenzoate, 2-cyanopropan-2-ylbenzodithioate, S,S'-bis(α,α'-dimethyl-α''-acetic acid) trithiocarbonate, S,S'-p-(α,α'-dimethyl-α''-acetic acid) trithiocarbonate, and S-1-dodecyl-S'(α,α'-dimethyl-α''-acetic acid) trithiocarbonate.

7. The reaction of introducing a functional group in step S3 includes a reaction using an aminating reagent to produce a strong cation or weak cation exchange solid-phase extraction material having an amine group, a reaction using an oxidizing reagent to produce a weak anion exchange solid-phase extraction material having a carboxyl group, or a reaction using a sulfonating reagent to produce a strong anion exchange solid-phase extraction material having a sulfonic acid group; the aminating reagent is one or more of diethylamine, triethylamine, dimethylamine, trimethylamine, dimethylbutylamine, N-methylimidazole, 1,2-ethylenediamine, piperazine; the oxidizing reagent is one or more of hydrogen peroxide, potassium permanganate, and aluminum oxide; 6. The method for producing a solid-phase extraction material according to claim 5, wherein the sulfonation reagent is one or more of concentrated sulfuric acid, chlorosulfonic acid, and sulfamic acid.

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