Low-residue sampling material for small molecule drug detection and application of low-residue sampling material

Abstract

According to the low-residue sampling material for small-molecule drug detection and the application of the low-residue sampling material in small-molecule drug detection sampling, the sampling material has a continuous network framework structure, the density is 8.3-9.3 kg / m < 3 >, the aperture ratio is 99% or above, the framework diameter is 5-10 microns, and the sampling material has the advantages that the sampling material is high in density and high in porosity; the problem that the detection accuracy is influenced by low sampling effectiveness in the sampling transfer process before small molecule drug detection in the prior art can be effectively solved.

Description

Technical Field

[0001] The present invention relates to the technical field of small molecule drug detection, in particular to a low-residue sampling material for small molecule drug detection and application thereof in small molecule drug detection sampling. Background Art

[0002] At present, the commonly used body fluid sample collection generally adopts absorbent materials (absorbent elements). This absorbent material is dry at the beginning. Through the capillary or other characteristics of the absorbent element material, it can absorb liquid samples or fluid samples and keep the fluid samples in the absorbent element. The absorbent material can be any material that can absorb liquid, such as sponge, filter paper, polyester fiber, gel, non-woven fabric, cotton, polyester film, yarn, flocking, etc. Porous materials are used for collection, such as common sponges or filter papers. These absorbed samples are squeezed and released from the absorbent element. These released samples can be directly used to detect whether the sample contains the analyte of interest. Alternatively, these porous films with liquid samples are immersed in a processing liquid, so that the sample on the absorbent film can be eluted into the processing liquid, so that the analyte of interest in the sample can be better detected in the detection device.

[0003] However, part of the effective substances to be tested remain in the sampling tube due to adsorption problems, the sampling effectiveness is low, and they cannot be completely released for subsequent testing. Although a series of extrusion devices have been developed in the prior art, it is ultimately impossible to solve the adsorption problem of the adsorption material (such as porous material) in the sampling tube for small molecule drugs (such as small molecule drug components BUP, 6MAM, PCP, FEN, BZO, THC (PARENT and METABOLITE), among which the known THC adsorption is the most serious adsorption, and the recovery rate is about 20% or less. For this reason, saliva samples collected using sampling materials often have inaccurate results when tested, because the effective ingredients therein are not fully utilized and detected. This phenomenon has a great impact on the accuracy of the test. Summary of the invention

[0004] The purpose of the present invention is to provide a low-residue sampling material for small molecule drug detection to solve the problem of low sampling efficiency and affecting detection accuracy during the sampling and transfer process before small molecule drug detection in the prior art. In particular, the present invention provides the application of the sampling material in sampling small molecule drugs for detection.

[0005] The present invention adopts the following technical scheme: a low-residue sampling material for small molecule drug detection, having a continuous network skeleton structure and a density of 8.3-9.3 kg / m 3 , the opening rate is above 99% and the skeleton diameter is 5-10um.

[0006] The small molecule drugs described in the present invention refer to molecules with a molecular weight below 1000 Daltons (Da), especially molecules with a molecular weight of 237 to 468, including but not limited to small molecules of abused drugs, such as BUP (buprenorphine, 467.64), 6-MAM (6-monoacetylmorphine, 327.37), PCP (ketamine, 237.73), FEN (fentanyl, 336.46), BZO (benzodiazepine, 284.74), THC (tetrahydrocannabinol, 314.462, including PARENT and METABOLITE).

[0007] The continuous network skeleton structure described in the present invention has skeleton nodes interconnected to form a network structure, which provides sufficient adsorption performance for the sampling material; at the same time, the effective opening rate and skeleton diameter ensure the effective extrusion of the sample, reduce residue, and make the sample detection have a higher recovery rate.

[0008] Further, the materials with continuous network skeleton structure include polyurethane foam, melamine foam, activated carbon, polydimethylsiloxane sponge, modified silica gel, polyester fiber, polyester film. Among them, melamine foam (melamine foam) is a foam-like material composed of melamine formaldehyde condensate.

[0009] In certain embodiments of the present invention, the melamine foam is prepared by the following preparation method: melamine foam is impregnated with a hydrophobically modified emulsion, then emulsion polymerization is performed under heating conditions, nano-microspheres are grown in situ on the melamine foam skeleton, and finally super-hydrophobic modified melamine foam is obtained by washing and drying, wherein the hydrophobically modified emulsion includes a modified monomer, an initiator, a cross-linking agent, an emulsifier, a low surface energy modifier, a solvent and water; on the one hand, the ultra-large porosity of this continuous network skeleton structure can provide sufficient capillary force to fully absorb the test sample, and on the other hand, through the hydrophobic modification of the melamine foam, it can more effectively release the sample under extrusion, further reducing the residue.

[0010] The preparation method of the hydrophobically modified emulsion comprises the following steps: dispersing an initiator in deionized water, adding a modified monomer, a crosslinking agent, an emulsifier and a low surface energy modifier to obtain a mixed solution, and dispersing the mixed solution in a solvent to obtain a hydrophobically modified emulsion; in parts by weight, the hydrophobically modified emulsion comprises 21-30 parts of the modified monomer, 1 part of the initiator, 20-22 parts of the crosslinking agent, 10-16 parts of the emulsifier, and 4.3-8 parts of the low surface energy modifier.

[0011] The modified monomer is one of styrene, acrylic acid and methyl methacrylate; the low surface energy modifier is one of stearic acid and polydimethylsiloxane.

[0012] The initiator may be one of sodium persulfate and ammonium persulfate; the crosslinking agent may be one of divinylbenzene, N,N-methylenebisacrylamide, trimethylolpropane triacrylate, ethylene glycol dimethacrylate, and dipentaerythritol pentaacrylate.

[0013] The emulsifier is one of Span80, Tween80, hexadecyltrimethylammonium bromide, sodium dodecylsulfonate, and ethylene glycol fatty acid ester.

[0014] The solvent is one of anhydrous ethanol, tetrahydrofuran, N,N-dimethylformamide, dimethyl sulfoxide, dioxane and N-methylpyrrolidone.

[0015] The immersion treatment is specifically to immerse in the hydrophobically modified latex by ultrasonic for 10-60 minutes; the emulsion polymerization is specifically to react at 40-80° C. for 4-24 hours; and the drying treatment is specifically to dry at 40-100° C. by forced air for 8-24 hours.

[0016] Furthermore, the preparation method of the modified silica gel comprises the following steps:

[0017] Step (1) In a three-necked flask, pyridine and 2-methyl-1-butanol are added, and then the flask is placed in an ice-water bath. After cooling, p-toluenesulfonyl chloride is added, the temperature of the flask is controlled and stirred, and then the flask is stored in a refrigerator. The flask is taken out, placed in an ice-water bath, and distilled water is added and stirred. After the reaction is completed, ether is added for extraction, and the organic phase is collected, washed with hydrochloric acid and water, and then anhydrous sodium sulfate is added for drying, and filtered to obtain polymer 1;

[0018] Step (2) adding 4-(4-hydroxyphenyl)azobenzoic acid, sodium bicarbonate and dimethylacetamide to a three-necked flask, heating, stirring, cooling after all solids are dissolved, dripping polymer 1, heating, stirring, cooling after the stirring is completed, adding distilled water, and filtering to obtain polymer 2; adding polymer 2, potassium carbonate powder and potassium iodide to a three-necked flask in sequence, adding dimethylacetamide, dripping 6-chloro-1-hexanol to the reaction solution under stirring, heating, reacting, cooling after the reaction is completed, adding distilled water to the three-necked flask, filtering to obtain polymer 3;

[0019] Step (3) adding polymer 3, dichloromethane, 4-dimethylaminopyridine and methacrylic acid to a single-necked flask, stirring until completely dissolved, adding a mixed solution of dicyclohexylcarbodiimide and dichloromethane, heating, reacting, after the reaction is completed, filtering with suction, and rotary evaporating to obtain polymer 4; dissolving polymer 4 in a hydrofluoric acid solution, adding hydrogen peroxide, heating, stirring, reacting, after the reaction is completed, heating, filtering with suction, and obtaining a fluorine-containing chiral side chain azobenzene monomer;

[0020] Step (4) dissolving the obtained fluorine-containing chiral side chain azobenzene monomer in cyclopentanone, stirring until completely dissolved, then adding the mixed solution into liquid silica gel, stirring and mixing evenly, and vacuum freeze-drying to obtain a sampling material.

[0021] In the above process, the synthesis process of fluorine-containing chiral side chain azobenzene monomer is as follows:

[0022]

[0023] A fluorine-containing chiral side-chain azobenzene monomer is synthesized through the above reaction. A chiral molecular structure exists in the monomer. The chiral molecule has a specific spatial structure and can interact with small molecule drugs through chiral recognition, thereby increasing the desorption capacity of small molecule drugs. The interaction force between small molecule drugs and chiral molecules is weak, and they can be easily decomposed from the material by applying pressure or immersing in a solution. The spatial structure of the chiral molecule will limit the adsorption position of the small molecule drug in the material, making it easier to desorb. At the same time, the monomer structure also contains fluorine atoms, which have high electronegativity and form large chemical bonds with other atoms, thereby reducing the interaction force on the surface of the prepared material, reducing the surface energy of the material, and helping to weaken the interaction between the material and the small molecule drug, thereby increasing the desorption capacity of the small molecule drug.

[0024] In the above process, liquid silica gel is modified with fluorine-containing chiral side chain azobenzene monomer, and a sampling material is obtained by vacuum freeze drying. During the vacuum freeze drying process, water molecules in the liquid silica gel form ice crystals during the freezing process, and then the ice crystals are converted into water vapor by sublimation under a vacuum environment, so that the water molecules in the liquid silica gel are removed, and a sampling material with a porous structure is obtained. The pores can provide a larger surface area and more adsorption sites, thereby increasing the adsorption effect. Small molecule drugs diffuse into the pores and interact with the surface of the porous material to achieve the adsorption effect.

[0025] Furthermore, in the step (1), the usage ratio of pyridine, 2-methyl-1-butanol and p-toluenesulfonyl chloride is (80-90) mL: (8.5-8.7) g: (37.9-38.7) g, the cooling temperature is 0-1°C, the stirring time is 0-1h, the storage time is 10-12h, and the stirring time is 2-3h.

[0026] Furthermore, in the step (2), the usage ratio of 4-(4-hydroxyphenyl)azobenzoic acid, sodium bicarbonate, dimethylacetamide and polymer 1 is (2.3-2.5) g: (0.8-1.0) g: (25-30) mL: (2.8-3.2) g, the heating temperature is 90-100° C., the cooling temperature is 60-70° C., the heating temperature is 80-90° C., and the stirring time is 24-30 h.

[0027] Furthermore, in the step (2), the usage ratio of polymer 2, potassium carbonate powder, potassium iodide, 6-chloro-1-hexanol and dimethylamide is (1.0-1.3) g: (0.41-0.56) g: (0.007-0.008) g: (0.4-0.6) g: (25-35) mL, the heating temperature is 110-130° C., and the reaction time is 70-75 h.

[0028] Furthermore, in the step (3), the usage ratio of polymer 3, dichloromethane, 4-dimethylaminopyridine and methacrylic acid is (0.98-1.21) g: (26-32) mL: (0.04-0.05) g: (0.8-0.9) mL, the heating temperature is 30-35° C., the reaction time is 70-72 h, the heating temperature is 30-40° C., the reaction time is 3-5 h, and the heating temperature after the reaction is completed is 100-120° C.

[0029] Furthermore, in the step (4), the ratio of the amount of the fluorinated chiral side chain azobenzene monomer to the amount of the liquid silica gel is (3-5) g: (30-42) mL.

[0030] Furthermore, the sampling material with a continuous network skeleton structure is melamine foam. Experiments have shown that the use of melamine foam as a sampling material can ensure efficient absorption and, compared with the same type of foam materials, can significantly reduce residual extrusion, with unexpected technical effects. This may be due to the special polymer chain structure of melamine foam and the honeycomb network structure formed by its foaming. On the one hand, it can effectively adsorb more than 99% of dirt and molecules, and preferentially adsorb small molecule drugs larger than small molecule drugs, similar to marijuana, which hinders the absorption of marijuana small molecule drugs, thereby effectively improving the recovery rate of effective substances.

[0031] The present invention also provides the application of the sampling material in the sampling of small molecule drugs, specifically: using the sampling material to adsorb a liquid sample containing small molecule drug molecules, and then squeezing out the liquid sample for testing.

[0032] The present invention also provides a highly efficient small molecule drug detection device, comprising:

[0033] A fluid sample collection element, comprising: a liquid absorbing element;

[0034] and, a desorption structure, which contacts the absorption element to release the liquid sample; including but not limited to a squeezing structure, squeezing the absorption unit;

[0035] and, a test element that is tested for a sample of the liquid released by the absorbent element.

[0036] The liquid absorption element adopts the aforementioned low-residue sampling material, which has a continuous network skeleton structure and a density of 8.3-9.3 kg / m 3 The opening rate is above 99%, the skeleton diameter is 5-10um, preferably melamine foam (melamine resin) and the above-mentioned fluorine-containing chiral side chain azobenzene monomer modified liquid silica gel, which can effectively improve the sample recovery rate.

[0037] The beneficial effects of the present invention are: the recovery rate of small molecule drugs (BUP, 6MAM, PCP, FEN, BZO, THC (PARENT and METABOLITE)) is high, and the detection rate can be effectively improved.

[0038] The fluorinated chiral side chain azobenzene monomer has a chiral molecular structure, which can interact with small molecule drugs through chiral recognition, increasing the desorption capacity of small molecule drugs. In addition, the spatial structure of the chiral molecule can limit the adsorption position of small molecule drugs in the material, making it easier to desorb. At the same time, the fluorine atoms in the fluorinated chiral side chain azobenzene monomer have high electronegativity, which can reduce the surface energy of the material, weaken the interaction between the material and small molecule drugs, further increase the desorption capacity of small molecule drugs, and reduce the residual rate of small molecule drugs in the sampling material. BRIEF DESCRIPTION OF THE DRAWINGS

[0039] Figure 1 This is a SEM image of the melamine foam used in this application;

[0040] Figure 2 This is the SEM image of the pva sponge;

[0041] Figure 3 This is the SEM image of the fiber sponge head;

[0042] Figure 4 It is the detection device used for detection in the embodiment. DETAILED DESCRIPTION

[0043] The present invention will be further described below in conjunction with the embodiments.

[0044] Example 1

[0045] In this embodiment, melamine resin (commercially available, with a density of 8.5 kg / m 3 , the opening rate is above 99%, the skeleton diameter is 5-10um, such as Figure 1 )、pva sponge head (density 11.6g / cm 3 ,like Figure 2 ), fiber sponge head (U.S. porex, diameter is about 20um, non-network skeleton such as Figure 3) constructs an absorption element to form the detection device described in patent No. CN201821145987.6. Specifically, the detection device includes a cavity 300 for accommodating a test element carrier and a cavity 200 for accommodating a test element carrier (such as Figure 4 As shown). The fluid collection element includes an absorption element 503 for absorbing the fluid sample and a gripping part 100 with a flexible sheet structure 102. The gripping part 100 includes a handheld part 101 and a plurality of ring-mounted flexible sheet structures 102 connected to the absorption element connection 503 through a connecting rod 502, thereby forming a specific fluid collection element. The absorption element 503 is placed in a person's mouth (for about 20 minutes) to collect saliva. The collection element absorbing the saliva sample is inserted into the cavity 300 accommodating the test element carrier through the opening of the cavity accommodating the test element carrier. As the collection element enters or is inserted, the liquid absorption element enters the receiving cavity. At this time, as the flexible sheet layer of the inner plug body gradually enters the opening of the cavity 300, it cooperates with the inner wall, allowing the absorption element 503 to be compressed in the extrusion cavity, thereby releasing the liquid sample and detecting the substance to be analyzed.

[0046] The product strips used for the detection and analysis of substances are:

[0047] 1) BUP: 5ng / ml colloidal gold test strips

[0048] 2) 6MAM: 10ng / ml colloidal gold test strip

[0049] 3) PCP: 10ng / ml colloidal gold test strip

[0050] 4) FEN: 10ng / ml colloidal gold test strip

[0051] 5) BZO: 10ng / ml colloidal gold test strip

[0052] 6)THC(PARENT):40ng / ml colloidal gold test strip

[0053] 7) THC (Metabolite): 12ng / ml colloidal gold test strips

[0054] Quality Control Products:

[0055] 1)BUP: 7.5ng / ml (+50% cutoff), 15ng / ml (3X cutoff)

[0056] 2) 6MAM: 15ng / ml (+50% cutoff), 30ng / ml (3X cutoff)

[0057] 3) PCP: 15ng / ml (+50% cutoff), 30ng / ml (3X cutoff)

[0058] 4)FEN: 15ng / ml (+50% cutoff), 30ng / ml (3X cutoff)

[0059] 5) BZO: 15ng / ml (+50% cutoff), 30ng / ml (3X cutoff)

[0060] 6)THC (PARENT): 60ng / ml (+50% cutoff), 120ng / ml (3X cutoff)

[0061] 7)THC (Metabolite): 18ng / ml (+50% cutoff), 36ng / ml (3X cutoff)

[0062] 8) Fresh non-drug saliva

[0063] Here’s how to do it:

[0064] DEVICE E: Soak various SWABs in the solution for about 20 minutes. After 20 minutes, squeeze out the solution and use a pipette to add samples (original standard products that have not been soaked in SWAB and various standard products that have been soaked in various SWABs) for comparative testing.

[0065] MIDSTREAM: Control: Remove SWAB and directly pipette sample addition test. Test group: Assemble SWAB in the DMISTREAM mold and perform sample addition test for comparison.

[0066] Table 1 BUP test results

[0067]

[0068]

[0069] Table 2 6MAM test results

[0070]

[0071]

[0072] Table 3 PCP test results

[0073]

[0074] Table 4 FEN test results

[0075]

[0076]

[0077] Table 5 BZO test results

[0078]

[0079]

[0080] Table 6 THC parent test results

[0081]

[0082] Table 7 THC (metabolite) test results

[0083]

[0084]

[0085] In summary: Melamine foam can effectively reduce the adsorption of BUP, 6MAM, PCP, FEN, BZO, THC (PARENT and METABOLITE) in small molecule drugs, with a recovery rate of more than 79%, effectively improving the detection rate.

[0086] Example 2

[0087] A super hydrophobic modified melamine foam in this embodiment is prepared by the following steps:

[0088] (1) dispersing 1 part by weight of a sodium persulfate initiator in 1000 parts by weight of deionized water to obtain a solution A containing sodium persulfate;

[0089] (2) dispersing 30 parts by weight of styrene, 22 parts by weight of divinylbenzene, 16 parts by weight of emulsifier Span80 and 4.3 parts by weight of stearic acid in 1001 parts by weight of solution A to obtain a mixed solution B;

[0090] (3) dispersing the mixed solution B in anhydrous ethanol to obtain a hydrophobically modified emulsion;

[0091] (4) 5 parts by weight of melamine foam was ultrasonically immersed in the above hydrophobically modified emulsion for 64 minutes, followed by reaction at 65° C. for 8.5 hours. The product was first washed with anhydrous ethanol and then dried at 50° C. for 10 hours to obtain super hydrophobically modified melamine foam.

[0092] Example 3

[0093] A super hydrophobic modified melamine foam in this embodiment is prepared by the following steps:

[0094] (1) dispersing 1 part by weight of sodium persulfate initiator in 1000 parts by weight of deionized water to obtain an initiator-containing solution A;

[0095] (2) dispersing 21 parts by weight of methyl methacrylate, 20 parts by weight of N,N-methylenebisacrylamide, 10 parts by weight of emulsifier Tween 80 and 8 parts by weight of stearic acid in 1001 parts by weight of solution A to obtain a mixed solution B;

[0096] (3) dispersing the mixed solution B in tetrahydrofuran to obtain a hydrophobically modified emulsion;

[0097] (4) 5 parts by weight of melamine foam (commercially available, density 8.7 kg / m 3 , the open porosity is above 99%, the skeleton diameter is 5-10um), ultrasonically immersed in the hydrophobic modified latex for 30 minutes, then reacted at 40°C for 24 hours, the product was first washed with anhydrous ethanol, and then dried at 100°C for 8 hours to obtain super hydrophobic modified melamine foam.

[0098] The superhydrophobic modified melamine foam obtained in Examples 2 and 3 was used to adsorb buprenorphine of known concentration, and the small molecule drug was desorbed by extrusion. The concentration of the desorbed small molecule drug was measured, and the residual rate was calculated. The residual rate of the sample obtained in Example 2 was 1.3%, and the residual rate of the sample obtained in Example 3 was 1.8%.

[0099] Example 4

[0100] The continuous network skeleton structure in the sampling material is mainly composed of silica gel modified with fluorinated chiral side chain azobenzene monomer. The preparation method of silica gel modified with fluorinated chiral side chain azobenzene monomer comprises the following steps:

[0101] Step (1) In a three-necked flask, 85 g of pyridine and 8.6 g of 2-methyl-1-butanol were added, and then the flask was placed in an ice-water bath. After cooling to 0° C., 38 g of p-toluenesulfonyl chloride was added, the temperature of the flask was controlled and stirred for 1 hour, and then the flask was placed in a refrigerator for 12 hours. The flask was taken out, placed in an ice-water bath, and distilled water was added and stirred for 3 hours. After the reaction was completed, ether was added for extraction, and the organic phase was collected, washed with hydrochloric acid and water, and then anhydrous sodium sulfate was added for drying, and filtered to obtain polymer 1;

[0102] Step (2) 2.4 g of 4-(4-hydroxyphenyl)azobenzoic acid, 0.9 g of sodium bicarbonate and 27 mL of dimethylacetamide were added to a three-necked flask, heated to 100° C., stirred, and after all the solids were dissolved, the temperature was lowered to 60° C., 3.0 g of polymer 1 was added dropwise, the temperature was raised to 90° C., stirred for 24 h, and after the stirring was completed, the mixture was cooled, distilled water was added, and suction was filtered to obtain polymer 2; 1.2 g of polymer 2, 0.5 g of potassium carbonate powder and 0.0075 g of potassium iodide were added to a three-necked flask in sequence, 30 mL of dimethylacetamide was added, 6-chloro-1-hexanol was added dropwise to the reaction solution under stirring, the mixture was heated to 120° C., reacted for 72 h, and after the reaction was completed, the mixture was cooled, distilled water was added to the three-necked flask, and suction was filtered to obtain polymer 3;

[0103] Step (3) 1.03 g of polymer 3, 30 mL of dichloromethane, 0.048 g of 4-dimethylaminopyridine and 0.85 mL of methacrylic acid were added to a single-necked flask, stirred until completely dissolved, and then a mixed solution of dicyclohexylcarbodiimide and dichloromethane was added, the temperature was raised to 30° C., and the reaction was performed for 72 h. After the reaction was completed, the mixture was filtered and rotary evaporated to obtain polymer 4; polymer 4 was dissolved in a hydrofluoric acid solution, hydrogen peroxide was added, the mixture was heated to 33° C., stirred, and reacted for 4 h. After the reaction was completed, the mixture was heated to 120° C., filtered, and vacuum evaporated to obtain a fluorine-containing chiral side chain azobenzene monomer;

[0104] Step (4) Dissolve the obtained 4 g fluorine-containing chiral side chain azobenzene monomer in cyclopentanone and stir until completely dissolved. Then add the mixed solution to 38 mL of liquid silica gel, stir and mix evenly, and vacuum freeze-dry to obtain a sampling material with a cross-linked network structure. The density of the sample is 8.3 kg / m 3 , the opening rate is above 99% and the skeleton diameter is 5-10um.

[0105] Example 5

[0106] The continuous network skeleton structure in the sampling material is mainly composed of silica gel modified with fluorinated chiral side chain azobenzene monomer. The preparation method of silica gel modified with fluorinated chiral side chain azobenzene monomer comprises the following steps:

[0107] Step (1) In a three-necked flask, 82 g of pyridine and 8.5 g of 2-methyl-1-butanol were added, and then the flask was placed in an ice-water bath. After cooling to 0° C., 38.1 g of p-toluenesulfonyl chloride was added, the temperature of the flask was controlled and stirred for 1 hour, and then the flask was placed in a refrigerator for 12 hours. The flask was taken out, placed in an ice-water bath, and stirred for 3 hours after adding distilled water. After the reaction was completed, ether was added for extraction, and the organic phase was collected, washed with hydrochloric acid and water, and then dried with anhydrous sodium sulfate, and filtered to obtain polymer 1;

[0108] Step (2) 2.3 g of 4-(4-hydroxyphenyl)azobenzoic acid, 0.8 g of sodium bicarbonate and 25 mL of dimethylacetamide were added to a three-necked flask, heated to 100° C., stirred, and after all the solids were dissolved, the temperature was lowered to 60° C., 2.9 g of polymer 1 was added dropwise, the temperature was raised to 90° C., stirred for 24 h, and after the stirring was completed, the mixture was cooled, distilled water was added, and suction was filtered to obtain polymer 2; 1.1 g of polymer 2, 0.45 g of potassium carbonate powder and 0.0071 g of potassium iodide were added to a three-necked flask in sequence, 28 mL of dimethylacetamide was added, 6-chloro-1-hexanol was added dropwise to the reaction solution under stirring, the mixture was heated to 120° C., reacted for 72 h, and after the reaction was completed, the mixture was cooled, distilled water was added to the three-necked flask, and suction was filtered to obtain polymer 3;

[0109] Step (3) 0.99 g of polymer 3, 27 mL of dichloromethane, 0.042 g of 4-dimethylaminopyridine and 0.81 mL of methacrylic acid were added to a single-necked flask, stirred until completely dissolved, and then a mixed solution of dicyclohexylcarbodiimide and dichloromethane was added, the temperature was raised to 30° C., and the reaction was performed for 72 h. After the reaction was completed, the mixture was filtered and rotary evaporated to obtain polymer 4; polymer 4 was dissolved in a hydrofluoric acid solution, hydrogen peroxide was added, the mixture was heated to 33° C., stirred, and reacted for 4 h. After the reaction was completed, the mixture was heated to 120° C., filtered, and vacuum evaporated to obtain a fluorine-containing chiral side chain azobenzene monomer;

[0110] Step (4) Dissolve the obtained 3 g of fluorinated chiral side chain azobenzene monomer in cyclopentanone and stir until completely dissolved. Then add the mixed solution to 35 mL of liquid silica gel, stir and mix evenly, and vacuum freeze-dry to obtain a sampling material with a cross-linked network structure. The density of the sample is measured to be 9.3 kg / m 3 , the opening rate is above 99% and the skeleton diameter is 5-10um.

[0111] Example 6

[0112] The continuous network skeleton structure in the sampling material is mainly composed of silica gel modified with fluorinated chiral side chain azobenzene monomer. The preparation method of silica gel modified with fluorinated chiral side chain azobenzene monomer comprises the following steps:

[0113] Step (1) In a three-necked flask, 87 g of pyridine and 8.7 g of 2-methyl-1-butanol were added, and then the flask was placed in an ice-water bath. After cooling to 0° C., 38.6 g of p-toluenesulfonyl chloride was added, the temperature of the flask was controlled and stirred for 1 hour, and then the flask was placed in a refrigerator for 12 hours. The flask was taken out, placed in an ice-water bath, and distilled water was added and stirred for 3 hours. After the reaction was completed, ether was added for extraction, and the organic phase was collected, washed with hydrochloric acid and water, and then anhydrous sodium sulfate was added for drying, and filtered to obtain polymer 1;

[0114] Step (2) 2.5 g of 4-(4-hydroxyphenyl)azobenzoic acid, 1.0 g of sodium bicarbonate and 30 mL of dimethylacetamide were added to a three-necked flask, heated to 100° C., stirred, and after all the solids were dissolved, the temperature was lowered to 60° C., 3.1 g of polymer 1 was added dropwise, the temperature was raised to 90° C., stirred for 24 h, and after the stirring was completed, the mixture was cooled, distilled water was added, and suction was filtered to obtain polymer 2; 1.25 g of polymer 2, 0.54 g of potassium carbonate powder and 0.0078 g of potassium iodide were added to a three-necked flask in sequence, 32 mL of dimethylacetamide was added, 6-chloro-1-hexanol was added dropwise to the reaction solution under stirring, the mixture was heated to 120° C., reacted for 72 h, and after the reaction was completed, the mixture was cooled, distilled water was added to the three-necked flask, and suction was filtered to obtain polymer 3;

[0115] Step (3) Add 1.18 g of polymer 3, 31 mL of dichloromethane, 0.045 g of 4-dimethylaminopyridine and 0.87 mL of methacrylic acid to a single-necked flask, stir until completely dissolved, add a mixed solution of dicyclohexylcarbodiimide and dichloromethane, heat to 30° C., react for 72 h, and after the reaction is completed, filter with suction, and evaporate to obtain polymer 4; dissolve polymer 4 in a hydrofluoric acid solution, add hydrogen peroxide, heat to 33° C., stir, and react for 4 h. After the reaction is completed, heat to 120° C., filter with suction, and obtain a fluorine-containing chiral side chain azobenzene monomer;

[0116] Step (4) Dissolve the obtained 5 g fluorine-containing chiral side chain azobenzene monomer in cyclopentanone and stir until completely dissolved. Then add the mixed solution to 41 mL of liquid silica gel, stir and mix evenly, and vacuum freeze-dry to obtain a sampling material with a cross-linked network structure. The density of the sample is 8.9 kg / m 3 , the opening rate is above 99% and the skeleton diameter is 5-10um.

[0117] Comparative Example 1

[0118] In the preparation process of the sampling material, no fluorinated chiral side chain azobenzene monomer was used, and liquid silica gel was directly used, and other conditions were the same as those in Example 4;

[0119] The obtained test sample was adsorbed with 6-MAM of known concentration, and 6-MAM was desorbed by squeezing or soaking in liquid. The concentration of desorbed 6-MAM was measured and the residual rate was calculated. The test results are shown in the following table:

[0120] Example 4 Example 5 Example 6 Comparative Example 1 Residual rate / % 23.3 24.1 26.8 35.6

[0121] It can be seen from the test results in the table that the sampling materials prepared in Examples 2-4 of the present invention have a relatively low residual rate of small molecule drugs compared with existing products (PVA sponge head, fiber sponge head (Porex, USA). By comparing Comparative Example 1 with Examples 2-4, it can be seen that the addition of fluorinated chiral side chain azobenzene monomers can effectively reduce the residual rate of small molecule drugs.

Claims

1. A low-residue sampling material for small molecule drug detection, Characterized in that, It has a continuous network skeleton structure with a density of 8.3-9.3 kg / m 3 , the opening rate is above 99% and the skeleton diameter is 5-10um.

2. The application of the sampling material described in claim 1 in small molecule drug sampling, specifically: using the sampling material to adsorb a liquid sample containing small molecule drug molecules, and then extruding the liquid sample for testing.

3. The application of the sampling material described in claim 2 in small molecule drug sampling, Characterized in that, Materials with a continuous network skeleton structure include polyurethane foam, melamine foam, activated carbon, polydimethylsiloxane sponge, modified silica gel, polyester fiber, and polyester film.

4. The application of the sampling material described in claim 2 in small molecule drug sampling, Characterized in that, The preparation method of the hydrophobic modified emulsion includes the following steps: dispersing an initiator in deionized water, adding a modified monomer, a crosslinking agent, an emulsifier, and a low surface energy modifier to obtain a mixed solution, and dispersing the mixed solution in a solvent to obtain a hydrophobic modified emulsion; By weight, in the hydrophobic modified emulsion, there are 21 - 30 parts of modified monomer, 1 part of initiator, 20 - 22 parts of crosslinking agent, 10 - 16 parts of emulsifier, and 4.3 - 8 parts of low surface energy modifier; The modified monomer is one of styrene, acrylic acid, and methyl methacrylate; the low surface energy modifier is one of stearic acid and polydimethylsiloxane.

5. The application of the sampling material described in claim 3 in small molecule drug sampling, Characterized in that, The initiator can be one of sodium persulfate and ammonium persulfate; the crosslinking agent is one of divinylbenzene, N,N - methylenebisacrylamide, trimethylolpropane triacrylate, ethylene glycol dimethacrylate, and dipentaerythritol pentaacrylate.

6. The application of the sampling material described in claim 3 in small molecule drug sampling, Characterized in that, The emulsifier is one of Span80, Tween80, cetyltrimethylammonium bromide, sodium dodecylsulfonate, and ethylene glycol fatty acid ester.

7. A low-residue sampling material for small molecule drug detection described in claim 2, Characterized in that, The preparation method of the modified silica gel includes the following steps: Step (1) In a three-necked flask, add pyridine and 2 - methyl-1-butanol, then place the flask in an ice-water bath. After cooling, add p-toluenesulfonyl chloride, control the temperature of the flask and stir, then put it in the refrigerator for storage. Take out the flask, place it in an ice-water bath, add distilled water and stir. After the reaction is completed, add ether for extraction, collect the organic phase, wash it with hydrochloric acid and water, then add anhydrous sodium sulfate for drying, filter to obtain Polymer 1; Step (2) adding 4-(4-hydroxyphenyl)azobenzoic acid, sodium bicarbonate and dimethylacetamide to a three-necked flask, heating, stirring, cooling after all solids are dissolved, dripping polymer 1, heating, stirring, cooling after the stirring is completed, adding distilled water, and filtering to obtain polymer 2; adding polymer 2, potassium carbonate powder and potassium iodide to a three-necked flask in sequence, adding dimethylacetamide, dripping 6-chloro-1-hexanol to the reaction solution under stirring, heating, reacting, cooling after the reaction is completed, adding distilled water to the three-necked flask, filtering to obtain polymer 3; Step (3) adding polymer 3, dichloromethane, 4-dimethylaminopyridine and methacrylic acid to a single-necked flask, stirring until completely dissolved, adding a mixed solution of dicyclohexylcarbodiimide and dichloromethane, heating, reacting, after the reaction is completed, filtering with suction, and rotary evaporating to obtain polymer 4; dissolving polymer 4 in a hydrofluoric acid solution, adding hydrogen peroxide, heating, stirring, reacting, after the reaction is completed, heating, filtering with suction, and obtaining a fluorine-containing chiral side chain azobenzene monomer; Step (4) dissolving the obtained fluorine-containing chiral side chain azobenzene monomer in cyclopentanone, stirring until completely dissolved, then adding the mixed solution into liquid silica gel, stirring and mixing evenly, and vacuum freeze-drying to obtain a sampling material.

8. Use of the sampling material according to claim 7 in sampling of small molecule drugs, It is characterized in that In the step (1), the usage ratio of pyridine, 2-methyl-1-butanol and p-toluenesulfonyl chloride is (80-90) mL: (8.5-8.7) g: (37.9-38.7) g, the cooling temperature is 0-1° C., the stirring time is 0-1 h, the storage time is 10-12 h, and the stirring time is 2-3 h.

9. Use of the sampling material according to claim 7 in sampling of small molecule drugs, It is characterized in that In the step (2), the usage ratio of 4-(4-hydroxyphenyl)azobenzoic acid, sodium bicarbonate, dimethylacetamide and polymer 1 is (2.3-2.5) g: (0.8-1.0) g: (25-30) mL: (2.8-3.2) g, the heating temperature is 90-100° C., the cooling temperature is 60-70° C., the heating temperature is 80-90° C., and the stirring time is 24-30 h.

10. An efficient small molecule drug detection device, It is characterized in that include: A fluid sample collection element, comprising: a liquid absorbing element; and, a desorption structure that contacts the absorbent element to release the liquid sample; and, a test element that performs a test on a liquid sample released by the absorbent element; The liquid absorbing element adopts the sampling material described in claim 1.

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