Molecularly imprinted membrane of new psychoactive substance as well as preparation method and application of molecularly imprinted membrane

Abstract

The invention discloses a molecularly imprinted membrane of a new psychoactive substance and a preparation method and application of the molecularly imprinted membrane, the molecularly imprinted membrane comprises a membrane substrate and an adsorption material layer arranged on the membrane substrate, and the material of the adsorption material layer comprises 3, 3 ', 4', 4 '-tetramethyl-3, 3', 4 '-tetramethyl-3, 3'-tetramethyl-3, 3 '-tetramethyl-3, 3'- The molecularly imprinted polymer is prepared by using 2, 4-methylenedioxyphenylethylamine as an alternative template and using a bulk polymerization method. The novel molecularly imprinted membrane prepared by combining a molecularly imprinted technology and a separation technology is used as a membrane extraction material, and integrates the advantages of a membrane extraction technology and an imprinting technology, so that the problems that a membrane material is easy to pollute and low in selectivity are solved, and the novel molecularly imprinted membrane is suitable for being used as a membrane extraction material. The method shows the capability of accurately identifying a target analyte in the membrane separation process, has the advantages of high efficiency, stability, repeatability and the like, and provides a new technical means and potential application for identifying and detecting common forbidden drugs in a water body.

Description

Technical Field

[0001] This invention relates to the field of molecular imprinting technology, specifically to a molecularly imprinted membrane of a novel psychoactive substance, its preparation method, and its application. Background Technology

[0002] New psychoactive substances (NPS) refer to drugs that have not yet been clearly defined and prohibited, often synthesized by chemists by altering the structure of known substances. With the deepening of research into the abuse of illicit drugs, the abuse of NPS is constantly increasing. Among them, amphetamine-type illicit drugs, including ecstasy and methamphetamine, are hallucinogens and stimulants that cause serious harm to physical and mental health, easily leading to addiction and social problems. Synthetic cathinone (SC) is also one of the NPS, first appearing on the European illicit drug market in 2005, widely sold as "bath salts" or "plant-based foods," posing challenges to identification and detection. By slightly modifying their molecular structure, these drugs circumvent regulations and continue to be abused in the illicit drug market. Detecting residues of common illicit drugs such as amphetamine and synthetic cathinone in environmental water samples has always been a challenge. Efficient pretreatment techniques are essential for improving the sensitivity and selectivity of detection methods.

[0003] Solid-phase extraction (SPE) is a widely used sample pretreatment technique. In recent years, miniaturized SPE methods have attracted considerable attention, such as pipette tip SPE, solid-phase microextraction, microsyringe microextraction, and miniaturized SPE. However, the small particle size of the adsorbent material makes recycling difficult, limiting the application of solid-phase extraction technology. Membrane extraction technology has improved this situation. Membrane extraction is a separation and extraction technique that uses a semi-permeable membrane to separate components in a mixture. Membrane extraction typically involves processes such as diffusion, dissolution, filtration, or ion exchange through the semi-permeable membrane, allowing specific components of the mixture to pass through the membrane while other components remain on one side. Membrane extraction technology offers advantages such as continuity and ease of operation. However, it is easily contaminated by particulate matter or large organic molecules, requiring frequent cleaning or replacement, and it also suffers from poor selectivity for target analytes. Summary of the Invention

[0004] This invention addresses the aforementioned problems by researching and designing a novel molecularly imprinted membrane for psychoactive substances, its preparation method, and its applications. The technical means employed in this invention are as follows: A molecularly imprinted membrane for a novel psychoactive substance includes a membrane substrate and an adsorbent material layer disposed on the membrane substrate, wherein the adsorbent material layer is composed of a molecularly imprinted polymer prepared by bulk polymerization using 3,4-methylenedioxyphenylethylamine (HPEA) as an alternative template.

[0005] Furthermore, the membrane substrate has a pore size of 0.45±0.05μm and a thickness of 0.45±0.05μm, and the adsorbent material layer has a thickness of 30~60μm.

[0006] A method for preparing a molecularly imprinted membrane of a novel psychoactive substance according to the present invention includes the following steps: S1: Molecularly imprinted polymers (MIPs) were prepared by bulk polymerization using 3,4-methylenedioxyphenethylamine (HPEA) as a substitute template, methacrylic acid (MAA) as a functional monomer, ethylene glycol dimethacrylate (EGDMA) as a crosslinking agent, and azobisisobutyronitrile (AIBN) as an initiator. S2: The molecularly imprinted polymer obtained in step S1 is mixed with the adhesive solution and then coated onto the membrane substrate. After drying, a molecularly imprinted membrane is obtained. The mixing method is high-speed stirring or vortex oscillation.

[0007] Further, in step S2, the coating method is blade coating, and the membrane substrate is a porous filter membrane made of one or more of the following materials: polyethylene sulfone, polytetrafluoroethylene, polyvinylidene fluoride, or nylon.

[0008] Further, the adhesive solution is a 3%-10% Nafion solution. The molecularly imprinted polymer and the adhesive solution are mixed by dispersing the molecularly imprinted polymer in a mixed solvent and then ultrasonically treating it, followed by adding the adhesive solution dropwise and then ultrasonically mixing. The mixed solvent is ethanol, methanol, acetone, or a mixture of water and alcohol. The coating amount of the molecularly imprinted polymer on the membrane substrate is 2-8 mg / cm³. 2 .

[0009] A pretreatment filtration device for a novel psychoactive substance includes a housing with an inlet and an outlet, and a molecularly imprinted membrane of the novel psychoactive substance described in this invention is disposed between the inlet and the outlet, the molecularly imprinted membrane separating the inlet and the outlet.

[0010] Furthermore, the pretreatment filtration device includes an upper shell, a lower shell, a molecularly imprinted membrane, and a sealing ring. The inlet is located on the upper shell, the outlet is located on the lower shell, and the sealing ring is located at the edge of the molecularly imprinted membrane. The upper shell and the lower shell can be fixed to each other and the sealing ring and the molecularly imprinted membrane are pressed between the upper shell and the lower shell, so that a sealed space is formed between the upper shell and the lower shell, through which the medium can only enter and exit. The inlet can be sealed to a fluid drive device.

[0011] Furthermore, the upper housing includes a top and an internally threaded retaining ring and a first handwheel disposed on the outer periphery of the top. The inlet is disposed in the middle of the top. The lower housing includes a bottom and an externally threaded retaining ring and a second handwheel disposed on the outer periphery of the bottom. The outlet is disposed in the middle of the bottom. A support ring for pressing the molecularly imprinted membrane and the sealing ring is also provided on the outer periphery of the bottom. The support ring has a concave structure that cooperates with the sealing ring. The internally threaded retaining ring can be screwed onto the externally threaded retaining ring and press the sealing ring and the molecularly imprinted membrane between the top and the support ring. The bottom also has multiple support protrusions for supporting the molecularly imprinted membrane. A medium flow channel communicating with the outlet is formed between the multiple support protrusions. The fluid driving device is a syringe.

[0012] The application of a molecularly imprinted membrane of a novel psychoactive substance as described in this invention in the enrichment and extraction of novel psychoactive substances.

[0013] A method for enriching and extracting new psychoactive substances from water, using the pretreatment filtration device for new psychoactive substances described in this invention, includes the following steps: S1': The molecularly imprinted membrane was activated using an aqueous methanol solution and water; S2': Inject the liquid containing the target analyte into the inlet of the pretreatment filtration device and allow it to pass through the molecularly imprinted membrane; S3': Inject deionized water into the inlet of the pretreatment filtration device and let it pass through the molecularly imprinted membrane to wash away any residual interfering impurities on the membrane; S4': After drying the molecularly imprinted membrane obtained in step S3', elute it and collect the eluent; S5': Analyze the eluent.

[0014] In step S2', the pH is preferably adjusted to 4-8, with 8 being the most preferred.

[0015] Compared with existing technologies, the novel molecularly imprinted membranes (MIMs) prepared by combining molecular imprinting separation technology with the molecularly imprinted membranes of new psychoactive substances described in this invention, as membrane extraction materials, combine the advantages of membrane extraction and imprinting technologies to solve the problems of easy fouling and low selectivity of membrane materials. They exhibit the ability to accurately identify target analytes during membrane separation, shorten adsorption and desorption time, reduce material usage, increase the contact area between the material and the sample, and improve the reusability of the material. This achieves the goal of efficiently and selectively enriching and separating trace levels of multiple new psychoactive substances in water. They have the advantages of high efficiency, stability, and reproducibility, providing new technical means and potential applications for the identification and detection of common prohibited drugs in water. Attached Figure Description

[0016] Figure 1This is a schematic diagram of the pretreatment filtration device described in an embodiment of the present invention.

[0017] Figure 2 yes Figure 1 Top view.

[0018] Figure 3 yes Figure 2 AA sectional view.

[0019] Figure 4 This is a schematic diagram of the upper shell structure according to an embodiment of the present invention.

[0020] Figure 5 This is a schematic diagram of the lower housing structure according to an embodiment of the present invention.

[0021] Figure 6 yes Figure 5 Top view.

[0022] Figure 7 yes Figure 6 BB cross-sectional view.

[0023] Figure 8 This is a porosity diagram of molecularly imprinted membranes with different adsorption doses according to an embodiment of the present invention.

[0024] Figure 9 This is a graph showing the effect of adsorption dosage on the recovery rate of the target substance in an embodiment of the present invention.

[0025] Figure 10 This is a graph showing the effect of sample pH on the recovery rate of the target analyte in an embodiment of the present invention. Detailed Implementation

[0026] To illustrate the possible application scenarios, technical principles, implementable specific solutions, and achievable objectives and effects of this application in detail, the following description, in conjunction with the listed specific embodiments and accompanying drawings, provides a detailed explanation. The embodiments described herein are merely illustrative of the technical solutions of this application and are therefore intended to limit the scope of protection of this application.

[0027] Example 1: Preparation of MIMs A molecularly imprinted membrane for the enrichment and detection of amphetamine-type and synthetic cathinone-type novel psychoactive substances is proposed. 3,4-methylenedioxyphenethylamine (HPEA), which has similar properties and structures to amphetamine-type prohibited drugs and synthetic cathinone-type substances, is selected as a substitute template. The molecularly imprinted polymer of the substitute template is prepared using bulk polymerization. The specific preparation process is as follows: S1: First, measure 0.14 mL of HPEA into a reaction tube, add 0.34 mL of functional monomer MAA and 5.60 mL of acetonitrile, then add 3.80 mL of crosslinking agent EGDMA and 40.0 mg of initiator AIBN. Deoxygenate the solution under nitrogen for 2 hours for prepolymerization, and finally place it in a 60°C water bath for 24 hours for reaction.

[0028] S2: After polymerization, the resulting solid was crushed, ground, and sieved. Fine particles were then precipitated with acetone. The final material was treated with a methanol / acetic acid (90:10, v:v) mixed solution to remove the template. After washing with anhydrous ethanol, the material was dried at 70°C for 10 h to obtain a molecularly imprinted polymer with a diameter of 30–60 μm.

[0029] S3: Weigh 20 mg of MIPs, add 1 mL of ethanol to fully wet them, and sonicate in cold water for 15 min. Add an appropriate amount of 25 mg of 5% Nafion solution, and sonicate in cold water for 15 min. Apply the material mixture slurry to a 0.45 μm pore size nylon filter membrane (purchased from Haining Yibo Filter Material Factory) using a blade coating method. Cut the filter membrane to a diameter of 2.5 cm, and then dry it at 45℃ for 6 h to obtain a molecularly imprinted membrane.

[0030] The coating amount of the molecularly imprinted polymer on the membrane substrate is 2-8 mg / cm². 2 In this embodiment, for a membrane substrate with a diameter of 2.5±0.5cm, the amount of molecularly imprinted polymer coated on the membrane substrate is 15-25mg.

[0031] Example 2: Assembly of the pretreatment filtration device The MIMs prepared in Example 1 were placed between the upper and lower filter shells of a replaceable membrane filter with a size of 2.5 cm, and assembled into a molecularly imprinted membrane device. This device was then connected to a syringe to obtain a pretreatment filtration device.

[0032] like Figures 1 to 7 As shown, the pretreatment filtration device for novel psychoactive substances in this embodiment includes a housing with an inlet and an outlet. A molecularly imprinted membrane of the novel psychoactive substance described in this invention is disposed between the inlet and the outlet, and the molecularly imprinted membrane separates the inlet and the outlet.

[0033] Specifically, the pretreatment filtration device includes an upper housing 1, a lower housing 2, a molecularly imprinted membrane 3, and a sealing ring 4. The inlet 11 is located on the upper housing 1, the outlet 21 is located on the lower housing 2, and the sealing ring 4 is located at the edge of the molecularly imprinted membrane 3. The upper housing 1 and the lower housing 2 are mutually fixed, pressing the sealing ring 4 and the molecularly imprinted membrane 3 between them, thus forming a sealed space between the upper housing 1 and the lower housing 2 through which the medium can only enter and exit. In this embodiment, the upper layer of the molecularly imprinted membrane 3 is an adsorbent material layer, the lower layer is a membrane substrate, and the sealing ring 4 is located above the molecularly imprinted membrane 3. In this embodiment, the sealing ring 4 is a rubber ring.

[0034] The upper housing 1 includes a top 14, an internally threaded retaining ring 12 disposed on the outer periphery of the top 14, and a first handwheel 13. The inlet 11 is located in the middle of the top 14. The lower housing 2 includes a bottom 26, an externally threaded retaining ring 22 disposed on the outer periphery of the bottom 26, and a second handwheel 23. The outlet 21 is located in the middle of the bottom 26. A support ring 24 for pressing the molecularly imprinted membrane 3 and the sealing ring 4 is also provided on the outer periphery of the bottom 26. The support ring 24 has an inwardly recessed structure that mates with the sealing ring 4. The internally threaded retaining ring... The 12 can be screwed onto the external threaded retaining ring 22 and press the sealing ring 4 and the molecularly imprinted membrane 3 between the top and the support ring 24. In this embodiment, the top 14 is a conical structure. Preferably, the concave structure of the support ring 24 is arc-shaped, and the cross-section of the sealing ring 4 is elliptical or both the top and bottom surfaces are arc-shaped. In this way, when the upper shell 1 and the lower shell 2 are pressed together, the conical top surface 14 applies a radially inward component force to the sealing ring 4, while the arc-shaped bottom surface of the support ring applies a radially outward component force to the sealing ring, achieving a balance of forces and enhancing the sealing effect and stability. The bottom 26 is also provided with multiple support protrusions 25 for supporting the molecularly imprinted membrane 3. The multiple support protrusions 25 form a medium flow channel communicating with the outlet 21. The setting of the support protrusions 25 prevents the molecularly imprinted membrane 3 from falling off under the pressure of the medium. At the same time, the medium flow channel formed between the support protrusions 25 ensures the smooth discharge of the medium. The inlet 11 is connected to a fluid driving device. In this embodiment, the fluid driving device is a syringe.

[0035] Example 3: Testing of MIMs Structures 1. Effect of material quantity on membrane porosity The material content was optimized using molecularly imprinted membranes of different masses (5 mg, 15 mg, and 30 mg) with a mass ratio of MIP material to 5% Nafion solution of 1:5. After weighing, the molecularly imprinted membranes were immersed in 20 mL of ethanol solution at 25 °C for 10 h. The change in porosity of the molecularly imprinted membranes under different conditions was measured by weighing the wet membrane.

[0036] Porosity (ε) is calculated using the following formula:

[0037] In the formula: w1 and w2 are the masses of the membrane before and after immersion in ethanol, ρ m and ρ e These are the densities of the membrane and ethanol, respectively.

[0038] Figure 8 The porosity test results of the prepared membrane material are shown. The porosity ε gradually decreased from 48.7% at 5 mg to 34.1% at 30 mg. As the amount of material increased, the porosity of the molecularly imprinted membrane gradually decreased. Therefore, the presence of molecularly imprinted materials has a significant impact on the porosity of the filter membrane.

[0039] 2. Effect of adsorbent material amount on recovery rate To determine the optimal loading of adsorbent material in the membrane, molecularly imprinted membranes with coatings of 5 mg, 10 mg, 15 mg, 20 mg, and 30 mg of molecularly imprinted polymer adsorbent were prepared. 10 mL of an aqueous solution containing the four target drugs (10 ng / mL) was used as the sample solution, and the pH was adjusted to 8.0. The sample solution was then passed through the molecularly imprinted membrane at a flow rate of 1 mL / min. Elution was then performed with 3 mL of methanol / trifluoroacetic acid (98:2), and the eluent was collected. The results are as follows: Figure 9 As shown, when the amount of adsorbent material in the membrane is 20 mg, the recovery rate of the target substance reaches a high level of 84.1%~93.7%. Given that 20 mg can achieve excellent and stable extraction efficiency, 20 mg was finally selected as the optimal amount of adsorbent material.

[0040] Example 4: Optimization of Extraction Conditions for MIMs This embodiment aims to optimize the solid-phase extraction conditions of four prohibited drugs in water samples using molecularly imprinted membranes, specifically by examining the impact of the key parameter of sample solution pH on the recovery rate.

[0041] 1. Experimental Methods Take 5 mL of deionized water and add 50 μL of standard solutions of four target prohibited drugs with a concentration of 1 μg / mL to prepare a pre-adsorption solution with a concentration of 10.0 ng / mL. Activate the molecularly imprinted membrane (MIMs) using 3 mL of methanol / water (50:50, v:v) and 3 mL of water. Elute the dried MIMs membrane with 3 mL of elution solution, pushing 3 mL of methanol / trifluoroacetic acid (98:2) through the MIMs membrane at a rate of 1 mL / min. Elute the eluent by rotary evaporation until nearly dry. Finally, reconstitute with 500 μL of 50% methanol-water solution. Analyze the reconstituted solution and calculate the recovery rate.

[0042] 2. Effect of sample solution pH on recovery rate The pH of the solution before adsorption was adjusted to 4, 8, and 12, and extraction experiments were conducted to verify the effect of different pH conditions on the recovery rate. Figure 10 It can be seen that the target substance exhibits the highest recovery rate (104%~109%) at pH 8. Due to possible matrix enhancement effects or experimental system errors, the calculated recovery rate is slightly higher than 100%. Therefore, it is determined that the molecularly imprinted material has the optimal adsorption conditions at pH=8.

[0043] In summary, this invention develops a novel molecularly imprinted membrane by combining molecularly imprinted materials with a 0.45 μm pore size filter membrane, enabling the detection and analysis of four common prohibited drugs in wastewater and river water. The molecularly imprinted membrane device provided in this application has a simple assembly process, and the feasibility of the invention has been verified through spiked recovery experiments. It provides a new technical means and potential application for the identification and detection of common prohibited drugs in water bodies.

[0044] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A molecularly imprinted membrane of a new psychoactive substance, characterized in that, The molecularly imprinted membrane comprises a membrane substrate and an adsorbing material layer arranged on the membrane substrate, and the adsorbing material layer is made of a molecularly imprinted polymer prepared by using 3,4-methylenedioxyamphetamine as a substitute template and a bulk polymerization method.

2. The molecularly imprinted film of a new psychoactive substance according to claim 1, characterized in that, The pore size of the membrane substrate is 0.45±0.05 μm, the thickness of the membrane substrate is 0.45±0.05 μm, and the thickness of the adsorbing material layer is 30-60 μm.

3. A method for producing a molecularly imprinted membrane of a new psychoactive substance according to claim 1 or 2, characterized in that, The method comprises the following steps: S1: using 3,4-methylenedioxyamphetamine as a substitute template, methacrylic acid as a functional monomer, ethylene glycol dimethacrylate as a crosslinking agent, and azobisisobutyronitrile as an initiator, a molecularly imprinted polymer is prepared by using a bulk polymerization method; S2: the molecularly imprinted polymer obtained in step S1 is mixed with an adhesive solution and then coated on a membrane substrate, and then dried to obtain a molecularly imprinted membrane.

4. The method for producing a molecularly imprinted membrane of a new psychoactive substance according to claim 3, characterized by, In step S2, the coating method is blade coating, and the membrane substrate is a porous filter membrane made of one or more than two materials selected from polyvinyl sulfone, polytetrafluoroethylene, polyvinylidene fluoride and nylon.

5. The method for preparing a molecularly imprinted membrane of a new psychoactive substance according to claim 3, characterized by, The adhesive solution is a 3%-10% Nafion solution, the mixing method of the molecularly imprinted polymer and the adhesive solution is that the molecularly imprinted polymer is dispersed in a mixed solvent and subjected to ultrasonic treatment, the adhesive solution is added dropwise and then subjected to ultrasonic mixing, the mixed solvent is ethanol, methanol, acetone or a mixed solvent of water and alcohol, and the coating amount of the molecularly imprinted polymer on the membrane substrate is 2-8 mg / cm2.

6. A pre-treatment filtering device for new psychoactive substances, characterized by, The device comprises a shell, an inlet and an outlet are arranged on the shell, a molecularly imprinted membrane for a new psychoactive substance as claimed in claim 1 or 2 is arranged between the inlet and the outlet, and the molecularly imprinted membrane separates the inlet and the outlet.

7. The pre-treatment filtering device of novel psychoactive substances according to claim 6, characterized in that, The device comprises an upper shell, a lower shell, a molecularly imprinted membrane and a sealing ring, the inlet is arranged on the upper shell, the outlet is arranged on the lower shell, the sealing ring is arranged at the edge of the molecularly imprinted membrane, the upper shell and the lower shell can be fixed to each other and press the sealing ring and the molecularly imprinted membrane between the upper shell and the lower shell, so that a sealed space is formed between the upper shell and the lower shell, the medium can only enter and exit the sealed space through the inlet and the outlet, and the inlet can be sealingly connected with a fluid driving device.

8. The pre-treatment filtering device of novel psychoactive substances according to claim 7, characterized in that, The upper shell comprises a top portion, an inner thread fixing ring arranged on the outer periphery of the top portion and a first hand wheel, the inlet is arranged in the middle of the top portion, the lower shell comprises a bottom portion, an outer thread fixing ring arranged on the outer periphery of the bottom portion and a second hand wheel, the outlet is arranged in the middle of the bottom portion, a support ring for pressing the molecularly imprinted membrane and the sealing ring is further arranged on the outer periphery of the bottom portion, the support ring is provided with an inner recess structure matched with the sealing ring, the inner thread fixing ring can be screw-connected with the outer thread fixing ring and press the sealing ring and the molecularly imprinted membrane between the top portion and the support ring, a plurality of support protrusions for supporting the molecularly imprinted membrane are further arranged on the bottom portion, and a medium flow channel communicated with the outlet is formed between the plurality of support protrusions, and the fluid driving device is a syringe.

9. The molecularly imprinted membrane for a new psychoactive substance as claimed in claim 1 or 2 is used for enriching and extracting a new psychoactive substance.

10. A method of enriching and extracting new psychoactive substances in water, characterized in that, The device for pretreatment and filtration of a new psychoactive substance as claimed in claim 6, 7 or 8 comprises the following steps: S1': activating the molecularly imprinted membrane with methanol aqueous solution and water; S2': injecting a liquid containing the target analyte into the inlet of the pretreatment filter device and passing it through the molecularly imprinted membrane; S3': injecting deionized water into the inlet of the pretreatment filter device and passing it through the molecularly imprinted membrane to wash away the residual interfering impurities on the membrane; S4': drying the molecularly imprinted membrane obtained in step S3' and then eluting it to collect the eluate; S5': detecting the eluate.

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