WO2023082566A1 - 固相萃取材料及其制备方法与应用 - Google Patents

固相萃取材料及其制备方法与应用 Download PDF

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WO2023082566A1
WO2023082566A1 PCT/CN2022/091097 CN2022091097W WO2023082566A1 WO 2023082566 A1 WO2023082566 A1 WO 2023082566A1 CN 2022091097 W CN2022091097 W CN 2022091097W WO 2023082566 A1 WO2023082566 A1 WO 2023082566A1
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phase extraction
extraction material
solid
preparation
emulsion
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French (fr)
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周庆
张子昂
陈军霞
陈禹融
雷冲天
王冉秋
周伟伟
章礼斌
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南京大学
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    • B—PERFORMING OPERATIONS; TRANSPORTING
    • B01—PHYSICAL OR CHEMICAL PROCESSES OR APPARATUS IN GENERAL
    • B01J—CHEMICAL OR PHYSICAL PROCESSES, e.g. CATALYSIS OR COLLOID CHEMISTRY; THEIR RELEVANT APPARATUS
    • B01J20/00—Solid sorbent compositions or filter aid compositions; Sorbents for chromatography; Processes for preparing, regenerating or reactivating thereof
    • B01J20/281—Sorbents specially adapted for preparative, analytical or investigative chromatography
    • B01J20/282—Porous sorbents
    • B01J20/285—Porous sorbents based on polymers
    • C—CHEMISTRY; METALLURGY
    • C08—ORGANIC MACROMOLECULAR COMPOUNDS; THEIR PREPARATION OR CHEMICAL WORKING-UP; COMPOSITIONS BASED THEREON
    • C08F—MACROMOLECULAR COMPOUNDS OBTAINED BY REACTIONS ONLY INVOLVING CARBON-TO-CARBON UNSATURATED BONDS
    • C08F257/00—Macromolecular compounds obtained by polymerising monomers on to polymers of aromatic monomers as defined in group C08F12/00
    • C08F257/02—Macromolecular compounds obtained by polymerising monomers on to polymers of aromatic monomers as defined in group C08F12/00 on to polymers of styrene or alkyl-substituted styrenes
    • Y—GENERAL TAGGING OF NEW TECHNOLOGICAL DEVELOPMENTS; GENERAL TAGGING OF CROSS-SECTIONAL TECHNOLOGIES SPANNING OVER SEVERAL SECTIONS OF THE IPC; TECHNICAL SUBJECTS COVERED BY FORMER USPC CROSS-REFERENCE ART COLLECTIONS [XRACs] AND DIGESTS
    • Y02—TECHNOLOGIES OR APPLICATIONS FOR MITIGATION OR ADAPTATION AGAINST CLIMATE CHANGE
    • Y02P—CLIMATE CHANGE MITIGATION TECHNOLOGIES IN THE PRODUCTION OR PROCESSING OF GOODS
    • Y02P10/00—Technologies related to metal processing
    • Y02P10/20—Recycling

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  • the invention belongs to the field of solid-phase extraction, and in particular relates to a preparation method and application of a series of enhanced solid-phase extraction materials with uniform particle diameters.
  • the performance of the solid phase extraction packing is the key to the extraction efficiency.
  • the functional groups contained in the solid phase extraction packing can realize the enrichment of the compound through the force.
  • the solid phase extraction packing can be divided into molecular polymer matrix, bonded silica gel, inorganic Metal oxides and other enhanced solid-phase extraction packings, among which the enhanced solid-phase extraction packing has multiple functional groups, which can realize the extraction of compounds with multiple forces, making its application range wider than that of single-functional solid-phase extraction columns. wide.
  • Enhanced sorbents extract analytes based on their interactions with ions while efficiently retaining uncharged species through hydrophobic and hydrophilic interactions, thus a composite retention mode.
  • Enhanced ion exchange polymers can be divided into enhanced cation exchange adsorbents and enhanced anion exchange adsorbents according to their bonded ionic groups, and can be divided into strong ion exchange adsorbents according to the strength of their bonded groups and weak ion exchange adsorbents.
  • the seed swelling polymerization method is an important method to effectively combine the hydrophilic and hydrophobic skeletons. At the same time, this method can also ensure the monodispersity of the prepared microspheres and effectively ensure the particle size uniformity of the filler.
  • this method can also ensure the monodispersity of the prepared microspheres and effectively ensure the particle size uniformity of the filler.
  • there are still certain problems in the preparation of hydrophilic and lipophilic materials by seed polymerization as recorded in the patent literature of CN 102382227A, although the N-vinylpyrrolidone with uniform particle size is prepared by the seed swelling polymerization method and divinylbenzene monodisperse microspheres, but due to the strong hydrophilicity of N-vinylpyrrolidone, the proportion of its participation in the swelling polymerization reaction cannot be controlled, and the obtained polymer microspheres are more of the hydrophobic substance divinylbenzene Self-polymerization, and thus cannot guarantee that the product has better hydrophilicity, it
  • the purpose of the present invention is to overcome the defect that the proportion of hydrophilic monomer N-vinylpyrrolidone participating in the swelling polymerization reaction cannot be controlled in the traditional seed swelling polymerization technology.
  • the hydrophilic substance Before participating in the final polymerization N-vinylpyrrolidone has formed a prepolymer micelle with the hydrophobic monomer divinylbenzene, has hydrophobic properties, and can enter the activator dibutyl phthalate ( DBP), and then make the hydrophilic substance N-vinylpyrrolidone fully participate in the final polymerization reaction, realize the sufficient polymerization of the hydrophilic monomer N-vinylpyrrolidone and divinylbenzene, and provide the amphiphilic resin microspheres A new aggregation scheme.
  • DBP activator dibutyl phthalate
  • Another object of the present invention is to successfully obtain a series of enhanced solid phase extraction materials with uniform particle size according to the above preparation method.
  • a preparation method of a solid phase extraction material comprising prepolymerizing monomers N-vinylpyrrolidone and divinylbenzene in the presence of a chain transfer agent, and then dropping them into an emulsion of monodisperse seed microspheres, and then performing swelling and reaction to prepare white balls
  • a chain transfer agent prepolymerizing monomers N-vinylpyrrolidone and divinylbenzene in the presence of a chain transfer agent, and then dropping them into an emulsion of monodisperse seed microspheres, and then performing swelling and reaction to prepare white balls
  • solid phase extraction materials are obtained.
  • the secondary swelling is usually only suitable for monomers with strong hydrophobicity such as styrene and divinylbenzene.
  • the ball first acts as a hydrophobic core in water to absorb the activator dibutyl phthalate (DBP), and then utilizes the hydrophobicity of DBP to absorb the hydrophobic monomer that participates in the secondary swelling.
  • DBP activator dibutyl phthalate
  • the secondary swollen monomers are polymerized near the seed microspheres.
  • N-vinylpyrrolidone a highly hydrophilic substance, which is very soluble in water.
  • the prepolymerization link is added before the secondary swelling polymerization, and the hydrophilicity of the product obtained by prepolymerization is adjusted by adjusting the prepolymerization conditions, and the combination of the hydrophilic monomer N-vinylpyrrolidone and the hydrophobic monomer
  • the precursor of hydrophilic-lipophilic solid-phase extraction microspheres i.e. white balls
  • the precursor of hydrophilic-lipophilic solid-phase extraction microspheres i.e. white balls
  • solid phase extraction microspheres i.e. white balls
  • the white balls refer to the hydrophilic balls prepared by prepolymerizing the monomers N-vinylpyrrolidone and divinylbenzene in the presence of chain transfer reagents, adding them dropwise to the emulsion of monodisperse seed microspheres, and then swelling and reacting. Lipophilic SPE microsphere precursor, the white spheres have not been processed to introduce functional groups.
  • the particle diameter of the monodisperse seed microspheres is in the range of 1-15 ⁇ m.
  • the pre-polymerization specifically includes monomer N-vinylpyrrolidone and divinylbenzene, emulsifier, free radical initiator, and chain transfer agent are added to the water phase and then ultrasonically strengthened to disperse to prepare emulsion B; emulsion B is prepared at a certain temperature Next pre-poly.
  • the mass ratio of the monomer N-vinylpyrrolidone to divinylbenzene is (1-81):9.
  • the mass of the emulsifier accounts for 0.1% to 20% of the total mass of the monomers; the mass of the free radical initiator accounts for 0.5% to 4% of the total mass of the monomers; the mass of the free radical initiator and the chain transfer agent
  • the molar ratio is 1:(1 ⁇ 2.8).
  • the mass ratio of monomer N-vinylpyrrolidone and divinylbenzene in the prepolymerization process is 1:1; the mass of the initiator accounts for 2% of the total mass of the monomer; the free radical initiator and chain transfer The molar ratio of the agent is 1:1.
  • RAFT chain transfer reagents while controlling the orderly polymerization of hydrophilic and hydrophobic monomers, by adjusting the ratio of hydrophilic and hydrophobic monomers, controlling the content of RAFT chain transfer reagents, controlling the temperature and time of prepolymerization and other prepolymerization reaction conditions,
  • the formed amphiphilic micelles are swollen into the vicinity of the seed microspheres to participate in polymerization, and then the precursor white balls of solid phase extraction microspheres with uniform particle size are prepared.
  • the preparation method specifically includes:
  • the stirring speed of the dispersion polymerization reaction is 100-1000 rpm
  • the temperature rise process of the dispersion polymerization reaction is 1-10° C. every 10 minutes
  • the reaction time is 4-12 hours;
  • the emulsion B is pre-polymerized at a certain temperature and then added dropwise to the emulsion A of the monodisperse seed microspheres, and the temperature is gradually raised after swelling at a low temperature.
  • the reaction speed is 100-800 rpm, and the heating process is Rise 1-10°C every 30 minutes, and the reaction time is 4-48 hours;
  • the free radical initiator in the step S1 or S2 is azobisisobutyronitrile, azobisisoheptanonitrile, dimethyl azobisisobutyrate, azobisisobutylamidine hydrochloride, azobisisobutyronitrile, One or more of nitrogen diisobutyl imidazoline hydrochloride, dibenzoyl peroxide, and benzoyl peroxide;
  • the emulsifier in the step S1 or S2 is an anionic emulsifier lauryl sulfate One or more of sodium, sodium dodecylbenzenesulfonate, fatty acid soap; and/or
  • the dispersant is one or more of polyethylene glycol, sodium hexametaphosphate, polyethylene glycol fatty acid ester, and polyvinylpyrrolidone;
  • the porogen is toluene, xylene, ethyl acetate
  • esters acetonitrile, tetrahydrofuran, acetone, n-hexane;
  • the dispersant used in step S1 is polyvinylpyrrolidone; the emulsifier is sodium lauryl sulfate, the initiator is azobisisobutyronitrile, and the porogen is toluene; and/or
  • the swelling agent is one of benzene, toluene, xylene, ethylene dichloride, chloroform, dimethyl phthalate, diethyl phthalate, and dibutyl phthalate. species or several;
  • the proportion of the dispersant added in the step S1 is 2%-10% of the monomer mass, preferably 2%-5%, more preferably 4%; and/or
  • the proportion of the initiator added in the 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 is controlled between 60°C and 95°C; and/or
  • the mass ratio of the monodisperse seed microspheres to the swelling agent is 1:2 to 1:10; and/or
  • the mass ratio of the swelling agent and the porogen in the step S1 is 1:1; and/or
  • the mass of the monodisperse seed microspheres in the emulsion A in the step S1 accounts for 1% to 5% of the total mass of the aqueous phase;
  • the monodisperse seed microspheres are added to the water phase in which the dispersant and emulsifier are dissolved, wherein the mass of the dispersant and emulsifier accounts for 0.2% to 25% and 0.1% to 20% of the mass of the monodisperse seed microspheres respectively ;and / or
  • the chain transfer reagent is 2-[dodecylthio (thiocarbonyl) thio]-2-methylpropionic acid, isobutyronitrile dithiobenzoate, 2-cyanopropyl-2 -ylbenzodithio, S,S'-bis( ⁇ , ⁇ '-dimethyl- ⁇ "-acetic acid) trithiocarbonate, S,S'-p-( ⁇ , ⁇ '-dimethyl- One or more of ⁇ "-acetic acid) trithiocarbonate, S-1-dodecyl-S'( ⁇ , ⁇ '-dimethyl- ⁇ "-acetic acid) trithiocarbonate.
  • S S'-bis( ⁇ , ⁇ '-dimethyl- ⁇ "-acetic acid) trithiocarbonate
  • the reaction of introducing functional groups in the step S3 includes the reaction of using an aminating reagent to prepare a strong cation or weak cation-exchange solid-phase extraction material with an amine group, or using an oxidizing reagent to prepare a weak anion-exchange solid-phase extraction material with a carboxyl group , or the reaction of using a sulfonating reagent to prepare a strong anion-exchange solid-phase extraction material with a sulfonic acid group.
  • the reaction of preparing a strong cation or weak cation exchange solid phase extraction material with amine groups can be to first use a chloromethylation reagent to prepare chlorine spheres with a chloromethyl active group, and then use an amination reagent and chlorine Sphere reaction to prepare strong cation or weak cation exchange solid phase extraction material with amine groups;
  • the reaction for preparing the strong anion-exchange solid-phase extraction material with sulfonic acid groups can be directly reacting white balls with sulfonating reagents;
  • S3 prepares solid phase extraction materials including:
  • the above-mentioned white ball is used as a raw material, and a sulfonating reagent is added to undergo a sulfonation reaction to obtain a strong anion exchange solid-phase extraction material.
  • the chloromethylation reagent is one or more of chloromethyl ether, bischloromethyl ether, methoxyacetyl chloride, and chloromethyl alkyl ether;
  • the oxidizing reagent is one or more of hydrogen peroxide, potassium permanganate, and aluminum oxide; the ratio of the mass of the oxidizing reagent to the mass of the chlorine ball is 0.5:1 to 50:1, preferably 0.5:1 to 20:1;
  • the sulfonating reagent is one or more of concentrated sulfuric acid, chlorosulfonic acid, and sulfamic acid; the ratio of the mass of the sulfonating reagent to the mass of the white ball is 1:1 to 100:1, preferably 1:1 to 10:1.
  • step S3 the rotational speed of the amination reaction is 100-800 rpm, the reaction temperature is 40-110° C., and the reaction time is 4-32 hours;
  • the oxidation reaction speed is 100-800rpm, the reaction temperature is 50-150°C, and the reaction time is 3-24h;
  • step S3 the rotational speed of the sulfonation reaction is 100-800 rpm, the reaction temperature is 80-140° C., and the reaction time is 4-48 hours.
  • the present invention also provides a solid phase extraction material prepared by the preparation method of the above solid phase extraction material, the solid phase extraction material includes strong cation or weak cation exchange solid phase extraction material with amine group, weak anion exchange Solid phase extraction material or strong anion exchange solid phase extraction material with sulfonic acid groups.
  • the acid selected in the above-mentioned cleaning process is one or more of formic acid, acetic acid, lactic acid, oxalic acid, and the concentration of the acid is preferably 0.1% to 25%;
  • the selected organic eluent in the above-mentioned elution process is methanol, acetonitrile, One or more of ethyl acetate;
  • the alkali used in the elution process is one or more of ammonia, dimethylamine, and trimethylamine, and the concentration of the alkali is preferably 0.1% to 25%.
  • the solid phase extraction material has an average particle diameter of 5-100 ⁇ m, a specific surface area of 300-1000 m 2 /g, and an exchange capacity of 0.1-5 mmol/g.
  • the present invention also provides the application of the above-mentioned solid phase extraction material in the extraction and enrichment of trace pollutants and charged pollutants in water.
  • the present invention provides a synthesis scheme in which hydrophilic monomers enter the oil phase to participate in the reaction through seed swelling, and use RAFT chain transfer reagents to orderly pre-polymerize hydrophilic monomers and hydrophobic monomers to form
  • the idea that amphiphilic micelles then participate in swelling is a new solution in this field, which solves the problem in the prior art that it is difficult to use hydrophilic monomers to prepare solid-phase extraction microspheres with uniform particle size through the seed swelling method.
  • the inventive preparation method can produce white balls with uniform particle size with a yield of more than 80%, has good hydrophilicity, and has high economic benefits;
  • the static contact angle of the white ball prepared in 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 °, in some embodiments the static contact angle is less than 75°, good hydrophilicity and uniform particle size, it is a good precursor for the subsequent preparation of solid phase extraction microspheres.
  • Each solid-phase extraction microsphere material prepared in the present invention has high extraction efficiency for corresponding substances, good data reproducibility, and good reusability.
  • Fig. 1 is the synthesis step in the embodiment of the present invention 1;
  • Fig. 3 is the contact angle figure of white ball in the embodiment of the present invention 1;
  • Fig. 4 is the white ball product photograph of embodiment 1 of the present invention.
  • the term "about” is used to provide flexibility and imprecision associated with a given term, measurement or value.
  • the degree of flexibility for a particular variable can be readily determined by one skilled in the art.
  • the static contact angle is measured by a DSA100 contact angle measuring instrument.
  • Emulsion A was prepared through 200W ultrasonic enhanced dispersion;
  • the temperature of the solution is raised to 80 °C by increasing 5 °C every 30 minutes, and the solution is stirred at 750rpm After reacting for 24 hours, the solution after the reaction was precipitated, filtered, washed repeatedly with methanol and water, and vacuum-dried for a certain period of time to obtain white balls with uniform particle size.
  • the static contact angle of the prepared white ball is 73.28°; the elemental analysis results show that the N element content of the white ball is 2.13%; the particle size distribution is 30-50 ⁇ m, and the specific surface area is 300-1200m 2 / g.
  • White balls were prepared in this example, and other conditions were the same as those in Example 1, except that the RAFT chain transfer reagent S,S'-bis( ⁇ , ⁇ '-dimethyl- ⁇ "-acetic acid) Trithiocarbonate was added in an amount of 0.69 g.
  • White balls were prepared in this example, and other conditions were the same as those in Example 1, except that the RAFT chain transfer reagent S,S'-bis( ⁇ , ⁇ '-dimethyl- ⁇ "-acetic acid) Trithiocarbonate was added in an amount of 0.92 g.
  • the static contact angle of white balls prepared by this method is 87.53°, and the elemental analysis results show that the content of N element is 0.9%, and the particle size distribution is 20-100 ⁇ m.
  • White balls were prepared in this example, and other conditions were the same as those in Example 1, except that the RAFT chain transfer reagent S,S'-bis( ⁇ , ⁇ '-dimethyl- ⁇ "-acetic acid) Trithiocarbonate was added in an amount of 1.15 g.
  • the static contact angle of white balls prepared by this method is 84.41°, the content of N element is 1.24%, and the particle size distribution is 20-200 ⁇ m.
  • White balls were prepared in this example, and other conditions were the same as those in Example 1, except that the prepolymerization time of emulsion B at 50°C was 1 hour.
  • the static contact angle of white balls prepared by this method is 89.87°, the content of N element is 0.77%, and the particle size distribution is 20-200 ⁇ m.
  • White balls were prepared in this example, and the other conditions were the same as those in Example 1, except that the prepolymerization time of emulsion B at 50°C was 3 hours.
  • the static contact angle of white balls prepared by this method is 89.00°, the content of N element is 0.49%, and the particle size distribution is 20-200 ⁇ m.
  • the static contact angle of white balls prepared by this method is 84.00°, the content of N element is 1.55%, and the particle size distribution is 20-200 ⁇ m.
  • the static contact angle of white balls prepared by this method is 84.89°, the content of N element is 0.49%, and the particle size distribution is 20-200 ⁇ m.
  • White balls are prepared in this comparative example, and other conditions are the same as the preparation method of white balls in Example 1, except that the RAFT chain transfer reagent is N-methyl-N-phenyl-dithiocarbamate cyanomethyl ester ( 0.46g).
  • the static contact angle of white balls prepared by this method is 96.06°, the content of N element is 0.22%, and the particle size distribution is 1-200 ⁇ m. Since the contact angle is greater than 90°, which is a hydrophobic contact angle, and the content of N element is extremely low, it is judged that the obtained polymer microspheres are mostly the self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone is not. Fully engaged in polymerization, reaction fails.
  • White balls were prepared in this comparative example, and the other conditions were the same as those in Example 1, except that the prepolymerization temperature of emulsion B was 40°C.
  • the static contact angle of white balls prepared by this method is 108.33°, the N element content is 0, and the particle size distribution is 1-200 ⁇ m. Since the contact angle is greater than 90°, which is a hydrophobic contact angle, and the N element content is 0, it is judged that the obtained polymer microspheres are more of the self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone Did not participate in the polymerization, the reaction failed.
  • White balls were prepared in this comparative example, and other conditions were the same as those in Example 1, except that the prepolymerization temperature of emulsion B was 60°C.
  • the static contact angle of white balls prepared by this method is 107.08°, the N element content is 0, and the particle size distribution is 1-200 ⁇ m. Since the contact angle is greater than 90°, which is a hydrophobic contact angle, and the N element content is 0, it is judged that the obtained polymer microspheres are more of the self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone Did not participate in the polymerization, the reaction failed.
  • White balls were prepared in this example, and other conditions were the same as those in Example 1, except that the RAFT chain transfer reagent S,S'-bis( ⁇ , ⁇ '-dimethyl- ⁇ "-acetic acid) Trithiocarbonate was added in an amount of 0.23 g.
  • the static contact angle of white balls prepared by this method is 99.52°, the content of N element is 0.47%, and the particle size distribution is 1-200 ⁇ m. Since the contact angle is greater than 90°, which is a hydrophobic contact angle, and the N element content is extremely low, it is judged that the obtained polymer microspheres are more of the self-polymerization of the hydrophobic substance divinylbenzene, and the hydrophilic substance N-vinylpyrrolidone Insufficient participation in polymerization, reaction failure.
  • Emulsion A was prepared through 200W ultrasonic enhanced dispersion;
  • Emulsion B was prepared by 200W ultrasonically intensified dispersion for 1 hour after phase phase; Emulsion B was added dropwise to Emulsion A, during which the stirring rate was kept at 200rpm. After the swelling was completed, the temperature of the solution was increased by 5° C. every 30 minutes to 80° C., and the reaction was carried out under stirring at 750 rpm for 24 hours. The reacted solution was precipitated, filtered, washed repeatedly with methanol and water, and vacuum-dried for a certain period of time to obtain white balls with uniform particle size.

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Abstract

本发明涉及固相萃取材料及其制备方法与应用，属于固相萃取领域，制备方法包括将单体N-乙烯基吡咯烷酮和二乙烯苯在链转移试剂存在下预聚后滴加入单分散种子微球的乳液中，再进行溶胀、反应制备白球的步骤，所述白球经引入官能团的反应，得到固相萃取材料。反应制得的固相萃取材料成球形貌好，比表面积大，离子交换容量高。制备的固相萃取材料在分离、富集PPCPs过程中多种作用力对物质共同发挥作用，萃取效率高，同时在洗脱过程中调节洗脱液的pH可以控制物质或者萃取材料的电离程度，进而对物质进行选择性分离。萃取实验结果表明，制备的固相萃取材料对物质的萃取回收率基本维持在85％-105％之间，且可以选择性地分离酸性、碱性、中性和两性物质。

Description

固相萃取材料及其制备方法与应用 技术领域
本发明属于固相萃取领域，具体涉及系列粒径均匀的增强型固相萃取材料的制备方法及应用。
背景技术
固相萃取填料的性能是影响萃取效率的关键，固相萃取填料包含的官能团可通过作用力来实现对化合物的富集，固相萃取填料又可以分为分子聚合物基质、键合硅胶、无机金属氧化物及其他增强型固相萃取填料，其中增强型固相萃取填料由于具有多种官能团，多种官能团实现多种作用力对化合物的萃取，使得其应用范围比单一官能团的固相萃取柱广。增强型吸附剂根据其与离子的相互作用提取分析物，同时通过疏水和亲水相互作用有效保留不带电荷的物质，因此是一种复合保留模式。在色谱测定之前，可以通过不同的洗脱液洗脱这些物理和化学性质差异很大的物质。增强型离子交换聚合物根据其键合的离子基团可以分为增强型阳离子交换吸附剂和增强型阴离子交换吸附剂，又根据其键合的基团的强弱可以分为强离子交换吸附剂和弱离子交换吸附剂。
Waters公司的HLB固相萃取小柱凭借其亲疏水骨架在对水体中痕量有机物的富集分离中得以广泛应用，但仍对许多有机物尤其是在水溶液中带电荷物质萃取回收率偏低，为此，Waters公司推出了MCX、MAX、WCX、WAX等一系列增强型产品作为补充，其特点为具有N-乙烯基吡咯烷酮-二乙烯苯的亲疏水骨架，且分别具有键合的磺酸、季胺、羧酸、哌嗪基团，对水体中带负电、带正电的有机物实现了较为优异的萃取效果。然而，相关产品的制备工艺均未公开。
种子溶胀聚合法是一种将亲疏水骨架有效结合的重要方法，同时，该方法还能保证制备微球的单分散性，有效保障了填料的粒径均一度。然而，目前种子聚合在制备亲水亲油材料过程中仍存在一定问题，如中国专利公开号为CN 102382227A的专利文献中记载，尽管通过种子溶胀聚合法制备出粒径均匀的N-乙烯基吡咯烷酮与二乙烯苯单分散微球，但是由于N-乙烯基吡咯烷酮具有较强的亲水性，其参与溶胀聚合反应的比例无法控制，得到的聚合物微球更多是疏水性物质二乙烯苯的自聚，进而无法保证产物具有较好的亲水性，以其作为前体物来制备改性填料并不经济且萃取性能不佳。因此，如何制备出粒径均匀的MCX、MAX、WCX、WAX是当前水体中痕量有机物高效前处理亟待突破的重要技术难题。
发明内容
1.要解决的问题
本发明的目的在于克服传统种子溶胀聚合技术中亲水性单体N-乙烯基吡咯烷酮参与溶 胀聚合反应的比例无法控制的缺陷，通过在二次溶胀聚合前增加了预聚环节，亲水性物质N-乙烯基吡咯烷酮在参与最终聚合前，已经与疏水性单体二乙烯苯形成了预聚物胶束，具有了疏水性质，可以通过相似相溶进入到活化剂邻苯二甲酸二丁酯(DBP)中，进而使亲水性物质N-乙烯基吡咯烷酮充分参与最终的聚合反应，实现亲水性单体N-乙烯基吡咯烷酮与二乙烯苯的充分聚合，为两亲性树脂微球提供了一种新的聚合方案。
本发明的另一目的在于根据上述的制备方法成功得到系列粒径均匀的增强型固相萃取材料。
本发明的再一目的在于提供了上述固相萃取材料的应用，对于水中酸性、碱性、中性和两性微量污染物具有优异的检测或者选择性分离效果。
2.技术方案
为了解决上述问题，本发明所采用的技术方案如下：
一种固相萃取材料的制备方法，包括将单体N-乙烯基吡咯烷酮和二乙烯苯在链转移试剂存在下预聚后滴加入单分散种子微球的乳液中，再进行溶胀、反应制备白球的步骤，所述白球经引入官能团的反应，得到固相萃取材料。
本发明制备固相萃取材料的思路是：先合成亲水亲油性固相萃取微球即白球，在此基础上引入具有离子交换作用的不同基团，制备出系列固相萃取填料；通过在亲水亲油骨架上的基团修饰，对应提升了酸性、碱性、中性、两性物质的萃取性能，适用于亲水性有机物的高效富集分离。
现有技术的种子溶胀聚合方法中，要保证良好的成球率与产率，二次溶胀通常只适用于苯乙烯、二乙烯苯等疏水性较强的单体，这是由于单分散种子微球首先在水中作为疏水核心，吸附活化剂邻苯二甲酸二丁酯(DBP)，进而利用DBP的疏水性，吸收参与二次溶胀的疏水性单体，这一步主要是利用了相似相溶的原理，最后在引发剂等物质存在的条件下，使二次溶胀的单体在种子微球附近发生聚合。而这一原理不适用于N-乙烯基吡咯烷酮这种亲水性极强的物质，这种物质在水中极易溶解，在溶胀过程中，倾向于溶解在水相，而不是以独立油相存在于体系中，因此很难通过相似相溶的原理被活化后的种子微球吸收并在附近参与聚合，因此在现有技术中一般不会采用N-乙烯基吡咯烷酮这种亲水性极强的单体通过溶胀聚合方法制备亲水性固相萃取微球。而本发明中，在二次溶胀聚合前增加了预聚环节，通过调节预聚的条件调整预聚得到产物的亲水性，成功实现了亲水性单体N-乙烯基吡咯烷酮与疏水性单体的充分聚合，得到了粒径均匀、产率较高且亲水性较好的亲水亲油性固相萃取微球前体(即白球)，并进一步通过引入官能团的反应制备出具有不同性能的固相萃取微球。
需要说明的是，白球指代将单体N-乙烯基吡咯烷酮和二乙烯苯在链转移试剂存在下预聚 后滴加入单分散种子微球的乳液中，再进行溶胀、反应制备得到的亲水亲油性固相萃取微球前体，该白球尚未经过引入官能团反应的处理。
优选地，所述白球的静态接触角小于90°，优选为小于85°，更优选小于80°，更优选为小于75°。
优选地，所述单分散种子微球粒径在1～15μm范围内。
优选地，所述预聚具体包括单体N-乙烯基吡咯烷酮和二乙烯苯、乳化剂、自由基引发剂、链转移试剂加入水相后超声强化分散制备得到乳液B；将乳液B在一定温度下预聚。
优选地，所述单体N-乙烯基吡咯烷酮与二乙烯苯的质量比为(1～81):9。
优选地，所述乳化剂质量占单体总质量的0.1％～20％；所述自由基引发剂质量占单体总质量的0.5％～4％；所述自由基引发剂与链转移剂的摩尔比为1:(1～2.8)。
优选地，所述预聚过程中单体N-乙烯基吡咯烷酮和二乙烯苯的质量比为1:1；所述的引发剂质量占单体总质量的2％；自由基引发剂与链转移剂的摩尔比为1:1。
优选地，所述乳液B预聚的温度为45～55℃；乳液B预聚的时间为1～24h；所述溶胀的温度为0～30℃；所述溶胀的时间为4～48h。
利用RAFT链转移试剂，在控制亲疏水单体进行有序聚合的同时，通过调整亲疏水单体的比例、控制RAFT链转移试剂添加的含量、控制预聚的温度和时间等预聚反应条件，将形成的两亲性胶束通过溶胀进入种子微球附近参与聚合，进而制备出粒径均匀的固相萃取微球前体白球。
优选地，制备方法具体包括：
S1制备单分散种子微球：将苯乙烯和二乙烯苯以一定比例混合作为油相，乙醇和水的混合物作为水相，在水相中加入分散剂和自由基引发剂，通过分散聚合反应制备得到单分散种子微球；将所述单分散种子微球加入溶有分散剂、乳化剂的水相中，并加入溶胀剂、致孔剂，经过超声强化分散制备得到乳液A；
S2制备白球：将单体N-乙烯基吡咯烷酮和二乙烯苯、乳化剂、自由基引发剂、链转移试剂加入水相后超声强化分散制备得到乳液B；将乳液B在一定温度下预聚后滴加入所述单分散种子微球的乳液A中，低温溶胀后逐渐升温，充分反应后出料、洗涤、干燥，得到白球；
S3制备固相萃取材料：所述白球经引入官能团的反应，得到固相萃取材料。
优选地，所述步骤S1中，分散聚合反应搅拌转速为100～1000rpm，分散聚合反应升温过程为每10分钟上升1～10℃，反应时间为4～12h；
优选地，步骤S2中，将乳液B在一定温度下预聚后滴加入所述单分散种子微球的乳液A中，低温溶胀后逐渐升温，此时的反应转速为100～800rpm，升温过程为每30分钟上升1～10℃， 反应时间为4～48h；
优选地，所述步骤S1或S2中自由基引发剂为偶氮二异丁腈、偶氮二异庚腈、偶氮二异丁酸二甲酯、偶氮二异丁脒盐酸盐、偶氮二异丁咪唑啉盐酸盐、过氧化二苯甲酰、过氧化苯甲酰中的一种或几种；所述步骤S1或S2中的乳化剂为阴离子型乳化剂十二烷基硫酸钠、十二烷基苯磺酸钠、脂肪酸皂中的一种或几种；和/或
所述步骤S1中分散剂为聚乙二醇、六偏磷酸钠、脂肪酸聚乙二醇酯、聚乙烯吡咯烷酮中的一种或几种；所述的致孔剂为甲苯、二甲苯、乙酸乙酯、乙腈、四氢呋喃、丙酮、正己烷中的一种或几种；
更优选地，步骤S1中所用分散剂为聚乙烯基吡咯烷酮；乳化剂为十二烷基硫酸钠、引发剂为偶氮二异丁腈、致孔剂为甲苯；和/或
所述步骤S1中溶胀剂为苯、甲苯、二甲苯、二氯乙烷、三氯甲烷、邻苯二甲酸二甲酯、邻苯二甲酸二乙酯、邻苯二甲酸二丁酯中的一种或几种；
所述步骤S1中水相中水与乙醇的质量比为15:85～85:15，优选为40:60～60:40，更优选为50:50；油相与水相的质量比为25:75-～75:25，优选为25:75；和/或
所述步骤S1中分散剂添加的比例为单体质量的2％～10％，优选为2％-5％，更优选为4％；和/或
所述步骤S1中引发剂添加的比例为单体质量的0.5～4％，优选为0.5％～-2％，更优选为1％；和/或
所述步骤S1中分散聚合反应温度控制在60～95℃之间；和/或
所述步骤S1中单分散种子微球与溶胀剂的质量比为1:2～1:10；和/或
所述步骤S1中溶胀剂和致孔剂的质量比为1:1；和/或
所述步骤S1中乳液A中单分散种子微球的质量占水相总质量的1％～5％；和/或
所述步骤S1中单分散种子微球加入溶有分散剂、乳化剂的水相中，其中分散剂和乳化剂质量分别占单分散种子微球质量的0.2％～25％和0.1％～20％；和/或
所述步骤S2中链转移试剂为2-[十二烷硫基(硫代羰基)硫基]-2-甲基丙酸、二硫代苯甲酸异丁腈酯、2-氰丙基-2-基苯并二硫、S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯、S,S’-对(α,α’-二甲基-α”-乙酸)三硫代碳酸酯、S-1-十二烷基-S’(α,α’-二甲基-α”-乙酸)三硫代碳酸酯中的一种或几种。更优选为S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯、S,S’-对(α,α’-二甲基-α”-乙酸)三硫代碳酸酯或S-1-十二烷基-S’(α,α’-二甲基-α”-乙酸)三硫代碳酸酯。
优选地，所述步骤S3中引入官能团的反应包括采用胺化试剂制备具有胺基的强阳离子或弱阳离子交换固相萃取材料的反应，或采用氧化试剂制备具有羧基的弱阴离子交换固相萃取 材料，或采用磺化试剂制备具有磺酸基团的强阴离子交换固相萃取材料的反应。
优选地，所述制备具有胺基的强阳离子或弱阳离子交换固相萃取材料的反应可以是首先采用氯甲基化试剂制备具有氯甲基活性基团的氯球，再采用胺化试剂与氯球反应制备具有胺基的强阳离子或弱阳离子交换固相萃取材料的反应；
优选地，所述制备具有羧基的弱阴离子交换固相萃取材料的反应可以是首先采用氯甲基化试剂制备具有氯甲基活性基团的氯球，再采用氧化试剂制备具有羧基的弱阴离子交换固相萃取材料的反应；
优选地，所述制备具有磺酸基团的强阴离子交换固相萃取材料的反应可以是直接将白球与磺化试剂反应；
即：
S3制备固相萃取材料包括：
以上述白球为原料，引入氯甲基活性基团，得到氯球；以氯球为原料，氯甲基被胺基取代得到强阳离子或弱阳离子交换固相萃取材料；或
以上述白球为原料，引入氯甲基活性基团，得到氯球；以氯球为原料，氯甲基发生氧化反应得到弱阴离子交换固相萃取材料；或
以上述白球为原料，加入磺化试剂发生磺化反应，得到强阴离子交换固相萃取材料。
所述氯甲基化试剂为氯甲醚、双氯甲醚、甲氧基乙酰基氯、氯甲基烷基醚中的一种或几种；
所述胺化试剂为二乙胺、三乙胺、二甲胺、三甲胺、二甲基丁胺、N-甲基咪唑、1,2-乙二胺、哌嗪中的一种或几种；所述胺化试剂的质量与氯球质量的比值为1:1～100:1，优选1:1～10:1；
所述氧化试剂为过氧化氢、高锰酸钾、氧化铝中的一种或几种；所述氧化试剂的质量与氯球质量的比值为0.5:1～50:1，优选0.5:1～20:1；
所述磺化试剂为浓硫酸、氯磺酸、氨基磺酸中的一种或几种；所述磺化试剂的质量与白球质量的比值为1:1～100:1，优选1:1～10:1。
优选地，步骤S3中，胺化反应的转速为100～800rpm，反应温度为40～110℃，反应时间为4～32h；
优选地，步骤S3中，氧化反应转速为100～800rpm，反应温度为50～150℃，反应时间为3～24h；
优选地，步骤S3中，磺化反应转速为100～800rpm，反应温度为80～140℃，反应时间为4～48h。
本发明还提供一种采用上述固相萃取材料的制备方法制备的固相萃取材料，所述固相萃 取材料包括具有胺基的强阳离子或弱阳离子交换固相萃取材料、具有羧基的弱阴离子交换固相萃取材料或具有磺酸基团的强阴离子交换固相萃取材料。
需要说明的是，不同种类的固相萃取材料的官能团不同，可以选择性的萃取不同性质的物质。针对pKa＜5.0的物质，可以选择弱阳离子交换材料，针对2＜pKa＜10的物质，可以选择强阴离子交换材料；清洗过程中加入酸溶液，洗脱过程分两步洗脱，第一步采用有机溶剂洗脱分离出中性物质，第二步采用混有碱的有机溶剂洗脱。针对pKa＞9的物质，可以选择弱阴离子交换材料，针对2＜pKa＜10的物质，可以选择强阳离子交换材料；清洗过程中加入碱溶液，洗脱过程分两步洗脱，第一步采用有机溶剂洗脱分离出中性物质，第二步采用混有酸的有机溶剂洗脱。
上述清洗过程中所选用的酸为甲酸、乙酸、乳酸、草酸中的一种或几种，酸的浓度优选0.1％～25％；上述洗脱过程所选用的有机洗脱剂为甲醇、乙腈、乙酸乙酯中的一种或几种；洗脱过程所选用的碱为氨水、二甲胺、三甲胺中的一种或几种，碱的浓度优选0.1％～25％。
优选地，所述的固相萃取材料平均粒径为5～100μm，比表面积为300～1000m 2/g，交换容量为0.1～5mmol/g。
本发明还提供了上述固相萃取材料在水中痕量污染物和带电污染物的萃取富集中的应用。
3.有益效果
相比于现有技术，本发明的有益效果为：
(1)本发明提供了一种将亲水性单体通过种子溶胀的方法进入油相参与反应的合成方案，使用RAFT链转移试剂将亲水性单体与疏水性单体有序预聚合形成两亲性胶束进而参与溶胀的思路，是本领域内全新的方案，解决了现有技术中难以采用亲水性单体通过种子溶胀方法制备均匀粒径固相萃取微球的问题，采用本发明的制备方法，制备得到粒径均匀的白球产率可以达到80％以上，具有良好的亲水性，经济效益高；
(2)本发明中制备的白球的静态接触角小于90°，在一些实施例中静态接触角小于85°，在一些实施例中静态接触角小于80°，在一些实施例中静态接触角小于75°，亲水性好且粒径均匀，是后续制备固相萃取微球反应良好的前体。
(3)本发明中白球经反应制备固相萃取微球的过程中，氯甲基化和胺化、磺化、氧化反应比较彻底，无副产物的出现，且重现性较好；得到的固相萃取微球的粒径分布均匀，粒径在30～50μm之间，均为球形，且微球表面含有丰富的孔道结构，有利于物质的传质，材料的比表面积大，离子交换容量高；
(4)本发明中制备的每一种固相萃取微球材料对相应的物质萃取效率高，数据重现性好，且重复利用性能好。
附图说明
图1为本发明实施例1中的合成步骤；
图2为本发明实施例1中制备的白球扫描电镜图；
图3为本发明实施例1中白球的接触角图；
图4为本发明实施例1的白球产品照片。
具体实施方式
除非另有定义，本文所使用的所有的技术和科学术语与属于本发明的技术领域的技术人员通常理解的含义相同；本文所使用的术语“和/或”包括一个或多个相关的所列项目的任意的和所有的组合。
实施例中未注明具体条件者，按照常规条件或制造商建议的条件进行。所用试剂或仪器未注明生产厂商者，均为可以通过市售购买获得的常规产品。
如本文所使用，术语“约”用于提供与给定术语、度量或值相关联的灵活性和不精确性。本领域技术人员可以容易地确定具体变量的灵活性程度。
浓度、温度、量和其他数值数据可以在本文中以范围格式呈现。应当理解，这样的范围格式仅是为了方便和简洁而使用，并且应当灵活地解释为不仅包括明确叙述为范围极限的数值，而且还包括涵盖在所述范围内的所有单独的数值或子范围，就如同每个数值和子范围都被明确叙述一样。例如，约1至约4.5的数值范围应当被解释为不仅包括明确叙述的1至约4.5的极限值，而且还包括单独的数字(诸如2、3、4)和子范围(诸如1至3、2至4等)。相同的原理适用于仅叙述一个数值的范围，诸如“小于约4.5”，应当将其解释为包括所有上述的值和范围。此外，无论所描述的范围或特征的广度如何，都应当适用这种解释。
本发明中静态接触角通过DSA100型接触角测定仪测定。
下面结合具体实施例对本发明进一步进行描述。
实施例1
(1)制备单分散种子微球：将15mL乙醇和15mL水混合作为水相，在水相中加入0.4g分散剂聚乙烯基吡咯烷酮和0.1g引发剂过氧化苯甲酰，60℃下搅拌30分钟至完全溶解；将8g苯乙烯和2g二乙烯苯混合作为油相逐滴加入水溶液中，待混合均匀后以每10分钟3℃的速率逐渐升温至75℃，搅拌速率保持在450～500rpm之间，反应4小时后得到粒径在5～10μm的单分散种子微球；
在100mL水溶液中加入0.5g分散剂聚乙烯基吡咯烷酮、0.375g乳化剂十二烷基硫酸钠、2g上述单分散种子微球、10g致孔剂甲苯、10g溶胀剂邻苯二甲酸二甲酯，经过200W超声强化分散制备得到乳液A；
(2)制备粒径均匀的白球：将二次聚合的单体10gN-乙烯基吡咯烷酮和10g二乙烯苯、0.375g乳化剂十二烷基硫酸钠、0.4g引发剂过氧化苯甲酰、0.46gRAFT链转移试剂S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯加入水相后200W超声强化分散1小时制备得到乳液B；将乳液B在50℃下预聚2小时后逐滴加入乳液A中，30℃下溶胀24小时，期间搅拌速率保持在200rpm。溶胀结束后，每30分钟上升5℃将溶液升温至80℃，在750rpm的搅拌下反应24小时。将反应后溶液沉淀、过滤，用甲醇和水反复冲洗之后，真空干燥一定时间，得到粒径均匀的白球。
通过DSA100型接触角测定仪测定，制备的白球的静态接触角为73.28°；元素分析结果表明，白球的N元素含量为2.13％；粒径分布为30～50μm，比表面积为300～1200m 2/g。
(3)制备增强型固相萃取材料：以上述白球10g加入50mL氯甲醚中，加入3.5g氯化铁作为催化剂，50℃、酸性条件下反应12小时引入氯甲基活性基团，得到氯球。
取一定量的氯球按照质量比1:3的比例加入三甲胺中，在60℃、300rpm的条件下反应24小时，得到强阳离子交换固相萃取材料MAX；
取一定量的氯球按照质量比1:3的比例加入二甲胺中，在70℃、300rpm的条件下反应24小时，得到弱阴离子交换固相萃取材料WAX；
取一定量的白球按照质量比1:3的比例加入浓硫酸中，在140℃、300rpm的条件下反应8小时，得到强阴离子交换固相萃取材料MCX；
取一定量的氯球按照质量比1:3的比例加入过氧化氢中，在80℃、300rpm的条件下反应8小时，得到弱阳离子交换固相萃取材料WCX。
实施例2
选取pH＝7的条件下呈现中性的物质：去甲替林(pKa＝9.7)、阿米替林(pKa＝9.4)、三氯生(pKa＝8.1)；和呈现酸性的物质：布洛芬(pKa＝4.9)、苯扎贝特(pKa＝3.6)、吲哚美辛(pKa＝4.5)作为选定的物质，选取实施例1中制备的强阳离子交换固相萃取材料：MAX。
(1)将500mg固相萃取材料填充至两头有筛板的6mL固相萃取柱中，分别称取适量上述药物，用甲醇溶解配成1g/L的标准储备液，分别吸取适量标准储备液配成1mg/L的混合标准使用液，与此同时配成1mg/L的混合内标使用液。
(2)用5mL甲醇活化和5mL水清洗固相萃取材料之后，过固相萃取柱，柱流速控制在10mL/min，过完柱后用5mL 5％的氨水清洗固相萃取柱，使酸性物质完全电离，呈现离子态，而后用5mL甲醇溶液将中性和碱性物质洗脱下来，最后用5mL 2％的甲酸甲醇溶液将酸性物质洗脱下来；将上述各洗脱液用氮吹仪吹至近干后，用乙腈定容至1mL。
(3)采用超高效液相色谱-串联质谱技术上机检测，以0.1％(v/v)甲酸水溶液和乙腈 作为流动相进行梯度洗脱，在电喷雾正离子模式下进行多反应监测(MRM)，内标法定量，回收率均在92.4％～103.8％之间。
选择Waters公司商用的
Figure PCTCN2022091097-appb-000001
MAX进行萃取实验，在相同的萃取检测条件下，回收率均在94.0％～102.9％之间。
实施例3
选取pH＝7的条件下呈现中性的物质：对乙酰氨基酚(pKa＝9.4)、三氯生(pKa＝8.14)、呈现两性的物质：氧氟沙星(pKa＝5.97，9.28)和呈现碱性的物质：克拉霉素(pKa＝9.0)、红霉素(pKa＝8.9)、奥美普林(pKa＝7.11)作为选定的物质，选取实施例1中制备的强阴离子交换固相萃取材料：MCX。
(1)将500mg固相萃取材料填充至两头有筛板的6mL固相萃取柱中，分别称取适量上述药物，用甲醇溶解配成1g/L的标准储备液，分别吸取适量标准储备液配成1mg/L的混合标准使用液，与此同时配成1mg/L的混合内标使用液。
(2)用5mL甲醇活化和5mL水清洗固相萃取材料之后，过固相萃取柱，柱流速控制在10mL/min，过完柱后用5mL 2％的甲酸清洗固相萃取柱，使碱性物质完全电离，呈现离子态，而后用5mL甲醇溶液将中性和酸性物质洗脱下来，最后用5mL 5％的氨水甲醇溶液将酸性物质洗脱下来；将上述各洗脱液用氮吹仪吹至近干后，用乙腈定容至1mL。
(3)采用超高效液相色谱-串联质谱技术上机检测，以0.1％(v/v)甲酸水溶液和乙腈作为流动相进行梯度洗脱，在电喷雾正离子模式下进行多反应监测(MRM)，内标法定量，回收率均在89.2％～103.1％之间。
选择Waters公司商用的
Figure PCTCN2022091097-appb-000002
MCX进行萃取实验，在相同的萃取检测条件下，回收率均在84.4％～98.9％之间。
实施例4
选取pH＝7的条件下呈现中性的物质：磺胺胍(pKa＝2.22,11.22)；和呈现酸性的物质：酮洛芬(pKa＝4.5)、水杨酸(pKa＝3.0)、磺胺甲恶唑(pKa＝1.6，5.7)作为选定的物质，选取实施例1中制备的弱阳离子交换固相萃取材料：WAX。
(1)将500mg固相萃取材料填充至两头有筛板的6mL固相萃取柱中，分别称取适量上述药物，用甲醇溶解配成1g/L的标准储备液，分别吸取适量标准储备液配成1mg/L的混合标准使用液，与此同时配成1mg/L的混合内标使用液。
(2)用5mL甲醇活化和5mL水清洗固相萃取材料之后，过固相萃取柱，柱流速控制在10mL/min，过完柱后用5mL 2％的甲酸清洗固相萃取柱，使固相萃取材料中的基团发生电离，呈现离子态，而后用5mL甲醇溶液将中性和碱性物质洗脱下来，最后用5mL 5％的氨水甲醇 溶液将酸性物质洗脱下来；将上述各洗脱液用氮吹仪吹至近干后，用乙腈定容至1mL。
(3)采用超高效液相色谱-串联质谱技术上机检测，以0.1％(v/v)甲酸水溶液和乙腈作为流动相进行梯度洗脱，在电喷雾正离子模式下进行多反应监测(MRM)，内标法定量，回收率均在85.2％～101.8％之间。
选择Waters公司商用的
Figure PCTCN2022091097-appb-000003
WAX进行萃取实验，在相同的萃取检测条件下，回收率均在86.8％-～100.2％之间。
实施例5
选取pH＝7的条件下呈现中性的物质：氯霉素(pKa＝11.0)、卡马西平(pKa＝13.94)、氟苯尼考(pKa＝10.73)；和呈现碱性的物质：阿米替林(pKa＝9.4)、阿替洛尔(pKa＝9.6)、沙丁胺醇(pKa＝10.3)作为选定的物质，选取实施例1中制备的弱阴离子交换固相萃取材料：WCX。
(1)将500mg固相萃取材料填充至两头有筛板的6mL固相萃取柱中，分别称取适量上述药物，用甲醇溶解配成1g/L的标准储备液，分别吸取适量标准储备液配成1mg/L的混合标准使用液，与此同时配成1mg/L的混合内标使用液。
(2)用5mL甲醇活化和5mL水清洗固相萃取材料之后，过固相萃取柱，柱流速控制在10mL/min，过完柱后用5mL 5％的氨水清洗固相萃取柱，使固相萃取材料中的基团发生电离，呈现离子态，而后用5mL甲醇溶液将中性和酸性物质洗脱下来，最后用5mL 2％的甲酸甲醇溶液将碱性物质洗脱下来；将上述各洗脱液用氮吹仪吹至近干后，用乙腈定容至1mL。
(3)采用超高效液相色谱-串联质谱技术上机检测，以0.1％(v/v)甲酸水溶液和乙腈作为流动相进行梯度洗脱，在电喷雾正离子模式下进行多反应监测(MRM)，内标法定量，回收率均在91.9％～105.2％之间。
选择Waters公司商用的
Figure PCTCN2022091097-appb-000004
WCX进行萃取实验，在相同的萃取检测条件下，回收率均在91.6％～104.6％之间。
实施例6
本实施例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，RAFT链转移试剂S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯的加入量为0.69g。
此方法制备的白球静态接触角为79.71°，N元素含量为1.10％，粒径分布为20～100μm。
实施例7
本实施例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，RAFT链转移试剂S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯的加入量为0.92g。
此方法制备的白球静态接触角为87.53°，元素分析结果表明：N元素含量为0.9％，粒径 分布为20～100μm。
实施例8
本实施例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，RAFT链转移试剂S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯的加入量为1.15g。
此方法制备的白球静态接触角为84.41°，N元素含量为1.24％，粒径分布为20～200μm。
实施例9
本实施例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，乳液B在50℃下预聚时间为1小时。
此方法制备的白球静态接触角为89.87°，N元素含量为0.77％，粒径分布为20～200μm。
实施例10
本实施例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，乳液B在50℃下预聚时间为3小时。
此方法制备的白球静态接触角为89.00°，N元素含量为0.49％，粒径分布为20～200μm。
实施例11
本对比例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，RAFT链转移试剂为S-1-十二烷基-S’(α,α’-二甲基-α”-乙酸)三硫代碳酸酯(0.46g)。
此方法制备的白球静态接触角为84.00°，N元素含量为1.55％，粒径分布为20～200μm。
实施例12
本对比例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，RAFT链转移试剂为S,S’-对(α,α’-二甲基-α”-乙酸)三硫代碳酸酯(0.46g)。
此方法制备的白球静态接触角为84.89°，N元素含量为0.49％，粒径分布为20～200μm。
对比例1
本对比例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，RAFT链转移试剂为N-甲基-N-苯基-二硫代氨基甲酸氰甲基酯(0.46g)。
此方法制备的白球静态接触角为96.06°，N元素含量为0.22％，粒径分布为1～200μm。由于接触角大于90°，为疏水性接触角，且N元素含量极低，判断得到的聚合物微球更多是疏水性物质二乙烯苯的自聚，亲水性物质N-乙烯基吡咯烷酮未充分参与聚合，反应失败。
对比例2
本对比例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，乳液B的预聚温度为40℃。
此方法制备的白球静态接触角为108.33°，N元素含量为0，粒径分布为1～200μm。由于 接触角大于90°，为疏水性接触角，且N元素含量为0，判断得到的聚合物微球更多的是疏水性物质二乙烯苯的自聚，亲水性物质N-乙烯基吡咯烷酮未参与聚合，反应失败。
对比例3
本对比例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，乳液B的预聚温度为60℃。
此方法制备的白球静态接触角为107.08°，N元素含量为0，粒径分布为1～200μm。由于接触角大于90°，为疏水性接触角，且N元素含量为0，判断得到的聚合物微球更多的是疏水性物质二乙烯苯的自聚，亲水性物质N-乙烯基吡咯烷酮未参与聚合，反应失败。
对比例4
本实施例中制备白球，其它条件与实施例1中白球的制备方法相同，不同之处在于，RAFT链转移试剂S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯的加入量为0.23g。
此方法制备的白球静态接触角为99.52°，且N元素含量为0.47％，粒径分布为1～200μm。由于接触角大于90°，为疏水性接触角，且N元素含量极低，判断得到的聚合物微球更多的是疏水性物质二乙烯苯的自聚，亲水性物质N-乙烯基吡咯烷酮未充分参与聚合，反应失败。
对比例5
(1)制备单分散种子微球：将15mL乙醇和15mL水混合作为水相，在水相中加入0.4g分散剂聚乙烯基吡咯烷酮和0.1g引发剂过氧化苯甲酰，60℃下搅拌30分钟至完全溶解；将8g苯乙烯和2g二乙烯苯混合作为油相逐滴加入水溶液中，待混合均匀后以每10分钟3℃的速率逐渐升温至75℃，搅拌速率保持在450-500rpm之间，反应4小时后得到粒径在5-10μm的单分散种子微球；
在100mL水溶液中加入0.5g分散剂聚乙烯基吡咯烷酮、0.375g乳化剂十二烷基硫酸钠、2g上述单分散种子微球、10g致孔剂甲苯、10g溶胀剂邻苯二甲酸二甲酯，经过200W超声强化分散制备得到乳液A；
(2)制备粒径均匀的白球：将二次聚合的单体10gN-乙烯基吡咯烷酮和10g二乙烯苯、0.375g乳化剂十二烷基硫酸钠、0.4g引发剂过氧化苯甲酰加入水相后200W超声强化分散1小时制备得到乳液B；将乳液B逐滴加入乳液A中，期间搅拌速率保持在200rpm。溶胀结束后，每30分钟上升5℃将溶液升温至80℃，在750rpm的搅拌下反应24小时。将反应后溶液沉淀、过滤，用甲醇和水反复冲洗之后，真空干燥一定时间，得到粒径均匀的白球。
此方法(不进行预聚)制备的白球静态接触角为100.97°，且N元素含量为0，粒径分布为1～200μm。由于接触角大于90°，为疏水性接触角，且N元素含量为0，判断得到的聚合物微球更多是疏水性物质二乙烯苯的自聚，亲水性物质N-乙烯基吡咯烷酮未参与聚合，反应 失败。以上内容是对本发明及其实施方式进行了示意性的描述，该描述没有限制性，实施例中所示的也只是本发明的实施方式之一，实际的实施方式并不局限于此。所以，如果本领域的普通技术人员受其启示，在不脱离本发明创造宗旨的情况下，不经创造性的设计出与该技术方案相似的实施方式及实施例，均应属于本发明的保护范围。

Claims (10)

  1. 一种固相萃取材料的制备方法，其特征在于：包括将单体N-乙烯基吡咯烷酮和二乙烯苯在链转移试剂存在下预聚后滴加入单分散种子微球的乳液中，再进行溶胀、反应制备白球的步骤，所述白球经引入官能团的反应，得到固相萃取材料。
  2. 根据权利要求1所述固相萃取材料的制备方法，其特征在于：所述预聚具体包括：将单体N-乙烯基吡咯烷酮和二乙烯苯、乳化剂、自由基引发剂、链转移试剂加入水相后超声强化分散制备得到乳液B；将乳液B在一定温度下预聚。
  3. 根据权利要求1所述固相萃取材料的制备方法，其特征在于：所述单体N-乙烯基吡咯烷酮与二乙烯苯的质量比为(1～81):9。
  4. 根据权利要求2所述固相萃取材料的制备方法，其特征在于：所述乳化剂质量占单体总质量的0.1～20％；所述自由基引发剂质量占单体总质量的0.5％～4％；所述自由基引发剂与链转移剂的摩尔比为1:(1～2.8)。
  5. 根据权利要求1～4中任意一项所述固相萃取材料的制备方法，其特征在于：所述乳液B预聚的温度为45～55℃；乳液B预聚的时间为1～24h；所述溶胀的温度为0～30℃；所述溶胀的时间为4～48h。
  6. 根据权利要求1～5中任意一项所述固相萃取材料的制备方法，其特征在于，具体包括：
    S1制备单分散种子微球：将苯乙烯和二乙烯苯以一定比例混合作为油相，乙醇和水的混合物作为水相，在水相中加入分散剂和自由基引发剂，通过分散聚合反应制备得到单分散种子微球；将所述单分散种子微球加入溶有分散剂、乳化剂的水相中，并加入溶胀剂、致孔剂，经过超声强化分散制备得到乳液A；
    S2制备白球：将单体N-乙烯基吡咯烷酮和二乙烯苯、乳化剂、自由基引发剂、链转移试剂加入水相后超声强化分散制备得到乳液B；将乳液B在一定温度下预聚后滴加入所述单分散种子微球的乳液A中，低温溶胀后逐渐升温，充分反应后出料、洗涤、干燥，得到白球；
    S3制备固相萃取材料：所述白球经引入官能团的反应，得到固相萃取材料。
  7. 根据权利要求6所述固相萃取材料的制备方法，其特征在于：
    所述步骤S1或S2中自由基引发剂为偶氮二异丁腈、偶氮二异庚腈、偶氮二异丁酸二甲酯、偶氮二异丁脒盐酸盐、偶氮二异丁咪唑啉盐酸盐、过氧化二苯甲酰、过氧化苯甲酰中的一种或几种；和/或
    所述步骤S1或S2中的乳化剂为阴离子型乳化剂十二烷基硫酸钠、十二烷基苯磺酸钠、脂肪酸皂中的一种或几种；和/或
    所述步骤S1中分散剂为聚乙二醇、六偏磷酸钠、脂肪酸聚乙二醇酯、聚乙烯吡咯烷酮中的一种或几种；所述的致孔剂为甲苯、二甲苯、乙酸乙酯、乙腈、四氢呋喃、丙酮、正己烷 中的一种或几种；和/或
    所述步骤S1中溶胀剂为苯、甲苯、二甲苯、二氯乙烷、三氯甲烷、邻苯二甲酸二甲酯、邻苯二甲酸二乙酯、邻苯二甲酸二丁酯中的一种或几种；和/或所述步骤S1中水相中水与乙醇的质量比为(15:85)～(85:15)；油相与水相的质量比为(25:75)～(75:25)；和/或
    所述步骤S1中分散剂添加的比例为单体质量的2％～10％；和/或
    所述步骤S1中引发剂添加的比例为单体质量的0.5％～4％；和/或
    所述步骤S1中分散聚合反应温度控制在60～95℃之间；和/或
    所述步骤S1中单分散种子微球与溶胀剂的质量比为(1:2)～(1:10)；和/或
    所述步骤S1中溶胀剂和致孔剂的质量比为1:1；和/或
    所述步骤S1中乳液A中单分散种子微球的质量占水相总质量的1％～5％；和/或
    所述步骤S1中单分散种子微球加入溶有分散剂、乳化剂的水相中，其中分散剂和乳化剂质量分别占单分散种子微球质量的0.2％～25％和0.1％～20％；和/或
    所述步骤S2中链转移试剂为2-[十二烷硫基(硫代羰基)硫基]-2-甲基丙酸、二硫代苯甲酸异丁腈酯、2-氰丙基-2-基苯并二硫、S,S’-二(α,α’-二甲基-α”-乙酸)三硫代碳酸酯、S,S’-对(α,α’-二甲基-α”-乙酸)三硫代碳酸酯、S-1-十二烷基-S’(α,α’-二甲基-α”-乙酸)三硫代碳酸酯中的一种或几种。
  8. 根据权利要求7所述固相萃取材料的制备方法，其特征在于：所述步骤S3中引入官能团的反应包括采用胺化试剂制备具有胺基的强阳离子或弱阳离子交换固相萃取材料的反应，或采用氧化试剂制备具有羧基的弱阴离子交换固相萃取材料的反应，或采用磺化试剂制备具有磺酸基团的强阴离子交换固相萃取材料的反应；
    所述胺化试剂为二乙胺、三乙胺、二甲胺、三甲胺、二甲基丁胺、N-甲基咪唑、1,2-乙二胺、哌嗪中的一种或几种；
    所述氧化试剂为过氧化氢、高锰酸钾、氧化铝中的一种或几种；
    所述磺化试剂为浓硫酸、氯磺酸、氨基磺酸中的一种或几种。
  9. 根据权利要求1～8所述固相萃取材料的制备方法制备的固相萃取材料，其特征在于：所述固相萃取材料包括具有胺基的强阳离子或弱阳离子交换固相萃取材料、具有羧基的弱阴离子交换固相萃取材料或具有磺酸基团的强阴离子交换固相萃取材料。
  10. 根据权利要求9所述固相萃取材料在水中痕量污染物和带电污染物的萃取富集中的应用。
PCT/CN2022/091097 2021-11-15 2022-05-06 固相萃取材料及其制备方法与应用 WO2023082566A1 (zh)

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