Preparation method of modified cotton fibers for selectively capturing synthetic cannabinoids in a gas sample and a matching collection device

Abstract

The application discloses a preparation method of modified cotton fibers for selectively capturing synthetic cannabinoids in a gas sample and a design of a matching collection device. The device comprises an air pump for providing a constant air flow, a sampling box, a collector, and sampling modified cotton fibers arranged in the shell of the collector. The sampling box comprises at least one inlet for connecting the air pump and at least one outlet for connecting the shell of the collector. The shell is arranged with synthetic sampling modified cotton fibers for capturing synthetic cannabinoid drugs in exhaled gas. The poly(MAA-co-EGDMA) modified cotton fibers prepared in the application have the selective capturing performance for trace synthetic cannabinoid drugs in exhaled gas and atmosphere (such as entertainment places and drug manufacturing places), realize the selective capturing of two synthetic cannabinoids in exhaled gas, and can be matched with a small mass spectrometer or a laboratory analysis instrument to realize the detection of trace drugs in exhaled gas.

Description

TECHNICAL FIELD

[0001] The present application relates to a kind of synthetic cannabinoid in gas sample trapping material and matching exhaled gas trapping device. Specifically, a kind of selective trapping exhaled gas MDMB-4en-PINACA and ADB-4en-PINACA poly (MAA-co-EGDMA) modified cotton fiber preparation method and the design of matching animal exhaled gas trapping device. BACKGROUND

[0002] Breath analysis has become an attractive disease diagnosis strategy, and has gained considerable attention due to its easy accessibility, easy sampling and non-invasiveness. Exhaled gas contains a variety of volatile and non-volatile compounds. Non-volatile drugs in exhaled breath can exist in the particulate phase as part of exhaled breath particles (EBP) or exhaled breath condensate (EBC), and thus can be used as a potential substrate for detecting abused drugs. This method also provides a potential solution to the psychological resistance often encountered when sampling suspected drug users.

[0003] Currently, the global drug crime problem is becoming increasingly serious, and the third generation of new psychoactive substances (NPS) is gradually spreading, and the public safety problem caused by it is becoming more and more prominent. Synthetic cannabinoid (SCs) is one of the most widely abused new psychoactive substances, which is potent, rapidly changing, low in price, strong in concealment, fast in metabolism and difficult to detect, and is often used as a substitute for natural cannabis by abusers. SCs were listed by the National Drug Control Commission on July 1, 2021.

[0004] Exhaled breath can be collected into various sampling canisters, gas sampling bags, syringes and sorbent tubes containing multiple cavities, or directly analyzed in analytical systems. However, the analytes in exhaled breath are highly diluted by carbon dioxide and water vapor (ppb to ppt levels), which poses a considerable challenge to analysis. In combination with traditional mass spectrometric analysis, a variety of sampling devices for collecting EBC and EBP have been developed. Although proven to be effective, these devices can be costly and not easily affordable for widespread use. More importantly, the compounds in the actual sample are diverse, which makes the current specific detection variable. How to selectively capture trace analytes from respiratory samples still remains a large obstacle to overcome. Selective capture of the desired analytes from complex respiratory samples can greatly reduce the influence of interfering substances. Using intermolecular forces to induce molecular aggregation or using probe molecules to selectively react and capture specific compounds is an extremely attractive method with great potential, especially in the field of respiratory analysis. The study of trapping materials can selectively capture specific compounds from respiratory samples, thereby increasing their concentration and facilitating subsequent analysis. In addition, its application in the collection of atmospheric samples in entertainment venues and drug manufacturing sites helps the drug suppression department to obtain evidence in real time and provides factual basis for sentencing. SUMMARY

[0005] The purpose of the present application is to provide a modified cotton fiber for selectively capturing synthetic cannabinoid drugs in gas samples. A poly(MAA-co-EGDMA) modified cotton fiber is designed and synthesized. Another purpose of the present application is to provide a preparation method of the modified cotton fiber. Another purpose of the present application is to provide a set of experimental animal exhaled breath trapping device loaded with the modified cotton fiber. The last purpose of the present application is to provide its application in trapping or detecting MDMB-4en-PINACA and ADB-4en-PINACA in exhaled breath.

[0006] Technical solution: The modified cotton fiber for selectively capturing MDMB-4en-PINACA and ADB-4en-PINACA according to the present application, the chemical modification is a poly(MAA-co-EGDMA) layer.

[0007] The chemically modified cotton fiber according to the present application, the cotton fiber is chemically modified with a poly(MAA-co-EGDMA) layer.

[0008] The preparation method of the chemically modified cotton fiber, comprising the following steps:

[0009] (1) Take cotton fiber, add methyl acrylate, dimethyl amino pyridine and N, N-dimethyl formamide, water bath heating, mechanical stirring for 6-18 hours, separate the esterified cotton fiber, wash, vacuum drying for standby;

[0010] (2) The esterified cotton fibers are immersed in an acetonitrile solution, ethylene glycol dimethacrylate (EGDMA) is added, heated, an initiator azobisisobutyronitrile (AIBN) is added, mechanical stirring is performed for 0.5-2 hours, the crosslinked cotton fibers are separated, washed, vacuum dried, and poly(MAA-co-EGDMA) modified cotton fibers are obtained.

[0011] The preparation method, the use amount ratio of the cotton fibers, methacrylic anhydride, dimethylamino pyridine and N,N-dimethyl formamide in step (1) is 0.2-0.5 g:3.0-5.0 g:0.2-0.3 g:50-100 mL.

[0012] The preparation method, the methacrylic anhydride in step (1) can be replaced by methacrylic acid, acrylic anhydride or acrylic acid; and the N,N-dimethyl formamide can be replaced by methanol, ethanol, DMSO or dichloromethane.

[0013] The preparation method, the use amount ratio of the esterified cotton fibers, EGDMA, AIBN and acetonitrile in step (2) is 0.2-0.5 g:4.0-6.0 g:5-10 mg:200-400 mL.

[0014] The preparation method, the heating temperature in step (2) can be 85-120℃.

[0015] An exhaled gas collection device matched with the chemically modified cotton fibers, comprising: an air pump, a sampling box and a collector; wherein the chemically modified cotton fibers are assembled in the collector in the form of sheets, clumps or other shapes.

[0016] A detection method using the exhaled gas collection device matched with the chemically modified cotton fibers, wherein the air pump, the sampling box and the collector are sequentially connected, the air pump is used to make the to-be-detected exhaled gas in the sampling box pass through the collector, the chemically modified cotton fibers in the collector are eluted, the eluent is blown dry in an air-tight manner, the eluent is redissolved, the supernatant is taken after centrifugation and is injected into a UHPLC-MS / MS for detection; the elution is performed using a methanol solution. The blowing dry in an air-tight manner is nitrogen blowing.

[0017] The exhaled gas collection device matched with the chemically modified cotton fibers, comprising three parts: an air pump, a sampling box and a collector.

[0018] ①The air pump at least comprises one outlet, which can be connected to the second part through a pipeline; the air pump can continuously output clean air at a constant flow rate.

[0019] The sampling box comprises a cavity, a partition plate removably attached to the inside of the cavity, a support removably attached to the bottom of the cavity, and sealing covers at both ends of the cavity; the cavity is configured to accommodate the exhaled gas to be tested or to accommodate experimental animals therein; the sealing cover comprises at least one outlet, and the opening and closing of the outlet are controlled by a switch; the sealing cover is provided with an O-ring to ensure the air tightness between the cavity and the sealing cover.

[0020] The collector comprises two detachable parts which form a cavity when combined, and the cavity can place chemically modified cotton fibers and at least temporarily accommodate or retain gas therein; each of the two parts comprises an outlet; one end of the outlet is connected to the sampling box through a pipeline, and the other end of the outlet is connected to a one-way valve.

[0021] The experimental animal exhaled gas collection device with the chemically modified cotton fiber is shown in Figure 9 The experimental animal exhaled gas collection device with the chemically modified cotton fiber is shown in

[0022] The chemically modified cotton fiber or the exhaled gas collection device with the chemically modified cotton fiber is used for synthesizing cannabinoid drugs in exhaled gas.

[0023] The chemically modified cotton fiber or the exhaled gas collection device with the chemically modified cotton fiber is used for synthesizing cannabinoid drugs in exhaled gas.

[0024] The application comprises the following steps: assembling the modified cotton fiber in the collector, connecting the pipeline between the air pump and the sampling box, placing the rat in the sampling box after injecting MDMB-4en-PINACA and ADB-4en-PINACA, connecting the pipeline between the sampling box and the collector, taking out the modified cotton fiber after the collection is completed, eluting with eluent, redissolving after nitrogen blowing, centrifuging to take supernatant, and injecting into UHPLC-MS / MS for detection. Further, the eluent is a methanol solution.

[0025] The modified cotton fiber in the application takes cotton fiber as a substrate, and utilizes the abundant hydroxyl groups on the surface thereof to perform esterification with methacrylate. A poly(MAA-co-EGDMA) layer is formed through further cross-linking of methacrylate with ethylene glycol dimethacrylate. The modification layer produces selective adsorption on target objects through hydrophobicity, hydrogen bonding and lone pair of electrons-π interaction. Through continuous experiments, the poly(MAA-co-EGDMA) modified cotton fiber has been successfully synthesized, and the optimal conditions for elution after capture, the capture performance on two target objects, the capture selectivity, the batch stability and the storage stability are determined. It is proved that the material has good selective capture effect on MDMB-4en-PINACA and ADB-4en-PINACA.

[0026] The reaction route is shown in Figure 1 The reaction route is divided into two steps. In the first step, the esterification on the surface of the fiber is performed with an excess of the compound of formula (II) in the presence of a solvent and by adding a suitable esterification catalyst. The compound of formula (III) is prepared by stirring the compound of formula (I) and the compound of formula (II) at room temperature to 100°C for 6-18 hours with or without pressure. The compound of formula (II) can be replaced by methacrylic acid, acrylic anhydride, acrylic acid, etc. In the second step, the compound of formula (V) is prepared by stirring the compound of formula (III) and the compound of formula (IV) at 85-120°C for 0.5-2 hours with or without pressure in the presence of a solvent and by adding a suitable amount of the compound of formula (IV) under the initiation of a catalyst AIBN. As the solvent for the above reaction, acetonitrile, N,N-dimethylformamide, dimethyl sulfoxide or dichloromethane is preferably used. Preferably, the reaction product of the first step and the reaction product of the second step are first washed with an organic solvent such as methanol, acetonitrile, ethanol, etc., and then washed with ultrapure water, and then dried at 60-100°C with or without vacuum. The modified cotton fiber can be used in the form of a lump, a sheet or other irregular shapes.

[0027] Beneficial effects: compared with the prior art, the present application has the following advantages: (1) the modified cotton material of the present application has good selective trapping effect on two cannabinoids MDMB-4en-PINACA and ADB-4en-PINACA in exhaled gas. The recovery rate of the modified cotton material of the present application to MDMB-4en-PINACA in exhaled gas is 10.8%, which is 1.7 times that of SensAbues film; the recovery rate to ADB-4en-PINACA is 9.7%, which is 1.8 times that of SensAbues film. (2) the chemical modification of the cotton fiber material of the present application is simple, the preparation cost is low, the repeatability is good; the stability is good, the trapping selectivity is strong, and it is suitable for the application of exhaled gas trapping experiment in scientific research. (3) the experimental animal exhaled gas collection device designed in the present application makes up for the current situation that there is lack of exhaled gas sample collection device for scientific research, can effectively collect the exhaled gas sample of experimental animals, can be popularized and widely used in scientific research. BRIEF DESCRIPTION OF DRAWINGS

[0028] Figure 1 Reaction scheme for the modified cotton fiber of the present application;

[0029] Figure 2 Fourier transform infrared (FT-IR) spectrum of the cotton fiber and different reaction processes of the present application;

[0030] Figure 3 X-ray photoelectron spectroscopy (XPS) spectrum of the cotton fiber and different reaction processes of the present application;

[0031] Figure 4 Trapping performance of the modified cotton fiber and SensAbues film to two synthetic cannabinoids;

[0032] Figure 5 Selectivity of the modified cotton fiber of the present application to MDMB-4en-PINACA and ADB-4en-PINACA;

[0033] Figure 6 Batch repeatability of the modified cotton fiber of the present application;

[0034] Figure 7 Stability of the modified cotton fiber of the present application;

[0035] Figure 8 MDMB-4en-PINACA and ADB-4en-PINACA gas-drug concentration-time curves obtained by applying the modified cotton fiber of the present application to rat exhaled gas trapping;

[0036] Figure 9 Design of the experimental animal exhaled gas collection device of the present application and combination with UHPLC-MS / MS;

[0037] Figure 10 Design drawing of experimental animal sampling box of the present application;

[0038] Figure 11 Schematic diagram for capturing MDMB-4en-PINACA and ADB-4en-PINACA in rat breath of the present application;

[0039] Figure 12 Graph of screening results of elution solvents in the elution step;

[0040] Figure 13 Graph of screening results of elution solvent volume in the elution step. DETAILED DESCRIPTION

[0041] The technical solutions of the present application will be further described in detail below in combination with the drawings and examples.

[0042] Example 1

[0043] Step one, add 3.2 cm diameter round cotton fibers (0.2 g), DMAP (0.3 g) and MAA (3.0 g) into DMF (50 mL). Place the whole system in a 60°C water bath, stir at 200 rpm for 12 h, so that MAA and the surface hydroxyl group of the cotton fiber undergo esterification reaction. Thoroughly rinse the fibers with acetone and deionized water, and then dry at 65°C under vacuum to obtain esterified cotton fibers.

[0044] Step two, immerse the prepared fibers in a solution containing acetonitrile (200 mL) and EGDMA (4.5 g), and heat the mixture from 60°C to boiling state. Add AIBN (5 mg), and keep boiling at 90°C for 1.5 h to crosslink MAA and EGDMA. Thoroughly wash the modified cotton fibers with acetonitrile and deionized water to remove unreacted ligands, and then dry at 65°C to obtain poly(MAA-co-EGDMA) modified cotton fibers.

[0045] Unmodified cotton fibers, esterified cotton fibers and poly(MAA-co-EGDMA) modified cotton fibers are characterized by FT-IR and XPS.

[0046] It is proved by Fourier infrared (FT-IR) characterization that MAA successfully undergoes esterification reaction with the surface hydroxyl group of the cotton fiber and that the poly(MAA-co-EGDMA) layer successfully modifies the surface of the cotton fiber, see Figure 2 The valence state of the surface elements of the material is analyzed by X-ray photoelectron spectroscopy (XPS), which further proves the successful modification of the poly(MAA-co-EGDMA) layer, and the results are shown in Figure 3

[0047] See​Figure 2 The characteristic band of hydrogen bond at 3300 cm -1 -1 disappeared after modification. The band at 1719 cm -1 -1 was assigned to the stretching vibration of C=O bond, which confirmed the formation of ester group during modification. It is worth noting that the cross-linking between MAA and EGDMA resulted in the shift of the band from 1719 cm -1 to 1727 cm -1 -1, which could be attributed to the loss of conjugation with C=C bond. Some characteristic bands appeared at 1574 cm -1 -1, which were related to the stretching mode of C=C (conjugated C=O) after the addition of MAA and EGDMA. The chemical groups on the surface of cotton fiber changed during modification. The characteristic signals in FT-IR indicated the success of modification.

[0048] Referring to Figure 3 , the XPS spectrum of cotton fiber had strong peaks at 533.1 and 285.1 eV, which were attributed to the binding energies of O1s and C1s, respectively. The C1s spectrum of cotton fiber could be deconvoluted into peaks at binding energies of 286.6 and 284.9 eV, which were attributed to *C-O and *C-C, respectively. On the other hand, the spectrum of MAA-modified cotton fiber contained additional peaks at 288.6 and 284.7 eV, which could be attributed to *C=O and *C=C derived from MAA. The cross-linking of MAA and EGDMA covered the surface of cotton fiber, resulting in the decrease of the intensity of C-O*and the increase of the intensity of C=O*due to C=C from EGDMA. The O1s spectrum of cotton fiber had a peak at 532.8 eV, which was attributed to C-O*. After modification, C=O*was introduced, resulting in a peak at a binding energy of 531.9 eV. In summary, X-ray photoelectron spectroscopy further confirmed the successful preparation of poly(MAA-co-EGDMA)-modified cotton fiber.

[0049] Example 2

[0050] The modified cotton fiber prepared in Example 1 was used to verify the trapping performance.

[0051] Step one, solution preparation

[0052] Preparation of the test solution: 100 μL of 100 μg / mL MDMB-4en-PINACA, ADB-4en-PINACA, and 5F-AMB (internal standard) reference stock solutions were placed in a 10 mL volumetric flask, and methanol was added to the mark. 100 μL of the above solution was placed in a 10 mL volumetric flask, and methanol was added to the mark to obtain the test solution.

[0053] Step two, preparation of simulated gas sample

[0054] Take 200 μL of the test solution and inject into a 1 L aluminum foil sampling bag. Blow human exhaled air into the bag through a one-way valve until the bag is full. Heat at 37 °C for 30 minutes to allow the test solution to fully evaporate.

[0055] Step three, trapping of simulated gas sample

[0056] Pre-wet the cotton fibers with 500 μL of methanol and assemble in the EB collector. Connect the EB collector to the outlet of the sampling bag and begin trapping. Gently press the sampling bag and slowly release the gas mixture until the bag is completely empty.

[0057] Step four, pre-treatment

[0058] Carefully remove the cotton fibers from the collector and transfer to a beaker. Then, add 3 mL of methanol to the beaker and vortex the mixture gently for 30 seconds. Transfer the eluate to a glass test tube. Repeat this process with another 3 mL of methanol and finally transfer the eluate to a glass tube. Dry the eluate under heating conditions (40 °C) with nitrogen gas (purity ≥ 99.999%) and then add 1 mL of 0.1% formic acid-acetonitrile solution (50:50, v / v) for reconstitution. Vortex the reconstitution solution for 1 minute and centrifuge at 10,000 rpm for 10 minutes. Take the supernatant for analysis.

[0059] Step five, preparation of control solution

[0060] Take another volume of the mixed solution in a glass test tube, add 6 mL of methanol, and perform the nitrogen blowing reconstitution operation as described in Step Four above. Take the supernatant for analysis.

[0061] Step six, analysis of pre-treated sample solution

[0062] Use UHPLC-MS / MS (Shimadzu 8060 ultra-high performance liquid chromatograph coupled with triple quadrupole mass spectrometer) to analyze the sample solution.

[0063] Liquid chromatography conditions: The chromatographic column is a Waters ACQUITY BEH C18 column (100 mm x 2.1 mm, 1.7 μm); mobile phase A is 0.1% formic acid aqueous solution, mobile phase B is acetonitrile; column temperature is 40 °C; flow rate is 0.3 mL / min; injection volume is 10 μL; gradient elution program is shown in Table 1.

[0064] Table 1. Chromatographic gradient elution program

[0065]

[0066] Mass spectrometry conditions: the ion source is ESI electrospray ion source; positive ion detection mode; the capillary voltage is 3.5 kV; the heating gas (N2) flow rate is 10 L / min; the atomizer gas (N2) flow rate is 3 L / min; the interface temperature is 300 DEG C; the dry gas (N2) flow rate is 10 L / min; the DL temperature is 250 DEG C; the heating block temperature is 400 DEG C; the scanning mode is MRM; the MRM monitoring channel of each test substance is determined according to the mass spectrometry scanning results, and Table 2 is specifically shown.

[0067] Table 2. MRM monitoring channel of each test substance

[0068]

[0069]

[0070] Step seven, calculation of absolute recovery rate

[0071] Absolute recovery rate (%) = (test substance peak area 1 * internal standard peak area 2) / (test substance peak area 2 * internal standard peak area 2) (test substance peak area 1, internal standard peak area 1 are the peak areas of the test substance and the internal standard in the captured sample, respectively, and test substance peak area 1, internal standard peak area 1 are the peak areas of the test substance and the internal standard in the pure solution, respectively). The absolute recovery rates of MDMB-4en-PINACA and ADB-4en-PINACA are calculated, respectively.

[0072] See Figure 4 It can be seen that the modified cotton fiber of the application has good capture performance on MDMB-4en-PINACA and ADB-4en-PINAC. Among them, the recovery rate of MDMB-4en-PINACA in exhaled gas is 10.8%, which is 1.7 times that of SensAbues membrane; the recovery rate of ADB-4en-PINACA is 9.7%, which is 1.8 times that of SensAbues membrane.

[0073] Example 3

[0074] The modified cotton fiber prepared in Example 1 is taken for capture selectivity verification.

[0075] Take 100 μg / mL of benzoyl ephedrine, MDMA, methamphetamine, cocaine, ketamine, morphine, codeine and amphetamine, 5F-AMB (internal standard) control stock solution 100 μL and place them in a 10 mL volumetric flask, and dilute to the mark with methanol. Take 100 μL of the above solution and place it in a 10 mL volumetric flask, and dilute to the mark with methanol, and the test substance solution is obtained.

[0076] According to the operation of steps two to seven in Example 2, the absolute recovery rates of the eight illegal drugs are calculated.

[0077] See Figure 5It can be known that the modified cotton fiber has good trapping performance on MDMB-4en-PINACA and ADB-4en-PINAC. The trapping performance of the modified cotton fiber on benzoyl ephedrine and codeine is weak, and the trapping performance on cocaine, ketamine, morphine, codeine and amphetamine is very weak or almost no trapping performance.

[0078] Example 4

[0079] Six batches of modified cotton fibers were continuously prepared according to the preparation method of the modified cotton fiber in Example 1.

[0080] According to the operation steps of Example 2, the absolute recovery rates of the six batches of cotton fibers on MDMB-4en-PINACA and ADB-4en-PINAC were determined respectively.

[0081] Referring to Figure 6 The trapping ability of the six batches of modified cotton fibers on MDMB-4en-PINACA and ADB-4en-PINAC has little difference, indicating that the repeatability of the modified cotton fiber in the present study is good.

[0082] Example 5

[0083] Multiple batches of modified cotton fibers were prepared at the same time according to the preparation method of the modified cotton fiber in Example 1.

[0084] According to the operation steps of Example 2, the absolute recovery rates of the cotton fibers on MDMB-4en-PINACA and ADB-4en-PINAC within 16 days were determined respectively.

[0085] Referring to Figure 7 The trapping performance of the modified cotton fiber in the present application slightly decreases within the storage period of 16 days, but remains relatively stable overall.

[0086] Example 6

[0087] Trapping of MDMB-4en-PINACA and ADB-4en-PINAC in the exhaled gas of rats by the modified cotton fiber prepared in Example 1

[0088] Step one, take 9 experimental rats and randomly allocate them into 3 groups, 3 rats in each group.

[0089] Step two, the control group is injected with 0.9% sodium chloride at a dose of 10 mL / kg by tail vein, and the experimental groups are injected with MDMB-4en-PINACA or ADB-4en-PINACA at a single dose of 5 mg / kg by tail vein.

[0090] Step three, place the mice in a self-made polypropylene (PP) sampling box (such as Figure 10The sampling chamber was sealed at both ends with O-ring sealed caps. The sampling chamber was carefully cleaned with high purity nitrogen prior to each use to minimize potential background contamination. The sampling chamber was connected to a gas pump at one end to pump clean dry air at a constant flow of 3 L / min to direct the mouse's exhaled breath into the EB collector with a one-way valve at one end. To mitigate any potential impact of the animal's feces, the mice were fasted and deprived of water for 12 hours prior to dosing, while clean tissue was placed in the rear of the mice to absorb urine and feces.

[0091] Step four, immediately after dosing, the mice were placed in the sampling chamber for a 15 minute collection period. Subsequently, the mice were quickly transferred to another sampling chamber and breath samples were collected for another 15 minutes. Using the established method, breath samples were collected from the mice at time intervals of 0-15 minutes, 15-30 minutes, 30-45 minutes, 45-60 minutes, 60-75 minutes, 75-90 minutes, 90-105 minutes, 105-120 minutes, 135-150 minutes, 165-180 minutes, 195-210 minutes, and 225-240 minutes after dosing. The trapping process was as described in Figure 11

[0092] Step five, after the breath gas samples were collected, the EB collector was disassembled and 50 μL of 5F-AMB solution was added to the cotton fibers. After this, the samples were analyzed as in Example 2, step four, post-treatment.

[0093] Step six, calculation of MDMB-4en-PINACA and ADB-4en-PINACA concentrations in samples

[0094] A working internal standard solution containing internal standard 5F-AMB at 2 ng / mL was prepared. A standard curve mix stock solution containing ADB-4en-PINACA at 0.1, 0.25, 0.5, 1, 2.5, 5, 12.5, 25 ng / mL and MDMB-4en-PINACA at 0.05, 0.125, 0.25, 0.5, 1.25, 2.5, 6.25, 12.5 ng / mL was prepared. 100 μL of each concentration of the standard curve mix stock solution and 100 μL of the internal standard solution were added to the EB breath collectors containing the blank breath matrix to prepare the spiked samples containing ADB-4en-PINACA at 10, 25, 50, 100, 250, 500, 1250, 2500 pg / filter and MDMB-4en-PINACA at 5, 12.5, 25, 50, 125, 250, 625, 1250 pg / filter. The spiked samples at each concentration were analyzed as in Example 2, step four, and 10 μL of each sample was injected. The concentrations of MDMB-4en-PINACA and ADB-4en-PINACA in the breath samples were determined according to the linear curve.​

[0095] Referring to Figure 8 The gas concentration of MDMB-4en-PINACA and ADB-4en-PINACA obtained by the application of modified cotton fibers to rats for breath capture increases and then decreases over time.

[0096] Example 7

[0097] Effect of eluent type and volume on elution.

[0098] The eluent type and volume are important factors affecting elution. The modified cotton fibers prepared in Example 1 were pretreated according to step four in Example 2, and the single-factor control method was used to investigate the eluent type and volume.

[0099] Methanol, acetonitrile, ethyl acetate, n-hexane and dichloromethane were investigated as elution solvents for their effect on elution. As shown in Figure 12 The data for the elution of MDMB-4en-PINACA, ADB-4en-PINACA and 5F-AMB by different solvents were combined, and methanol was ultimately selected as the elution solvent.

[0100] The greater the amount of eluent, the more complete the elution of the target substance, but it also dilutes the concentration of the target substance. Therefore, the effect of different elution volumes (2 mL + 2 mL, 3 mL + 3 mL, 4 mL + 4 mL) on elution was investigated, and the results are shown in Figure 13 When the elution volume was 3 mL + 3 mL, the effect was optimal, so the elution volume was selected to be 3 mL + 3 mL.

Claims

1. Use of chemically modified cotton fibers in the capture of synthetic cannabinoid drugs in exhaled breath, said cotton fibers being chemically modified with a poly(MAA-co-EGDMA) layer, said synthetic cannabinoid drugs being MDMB-4en-PINACA, ADB-4en-PINAC.

2. Use of chemically modified cotton fibers according to claim 1 in the trapping of synthetic cannabinoids in exhaled breath, characterized in that, The preparation of said chemically modified cotton fibers comprises the following steps: (1) Take cotton fibers, add methyl acrylate, dimethyl amino pyridine and N, N- dimethyl formamide, water bath heating, mechanical stirring for 6-18 hours, separate the esterified cotton fibers, wash, vacuum drying for standby; (2) The esterified cotton fibers are immersed in acetonitrile solution, ethylene glycol dimethyl acrylate (EGDMA) is added, heated, initiator azobisisobutyronitrile (AIBN) is added, mechanical stirring for 0.5-2 hours, separation of crosslinked cotton fibers, washing, vacuum drying, to obtain poly(MAA-co-EGDMA) modified cotton fibers.

3. Use according to claim 2, characterized in that, The amount ratio of cotton fibers, methyl acrylate, dimethyl amino pyridine and N, N- dimethyl formamide in step (1) is 0.2-0.5g:3.0-5.0g:0.2-0.3g:50-100mL.

4. Use according to claim 2, characterized in that, In step (1), methyl acrylate can be replaced by methyl acrylate, acrylate or acrylic acid; N, N-dimethyl formamide can be replaced by methanol, ethanol, DMSO or dichloromethane.

5. Use according to claim 2, characterized in that, The amount ratio of esterified cotton fibers, EGDMA, AIBN and acetonitrile in step (2) is 0.2-0.5g:4.0-6.0g:5-10mg:200-400mL.

6. Use according to claim 2, characterized in that, The heating temperature in step (2) is 85-120℃.

7. Use of a chemically modified cotton fiber outfitted exhaled breath collection device in the capture of cannabinoids in exhaled breath, the device comprising: Air pump, sampling box, collector; wherein the chemically modified cotton fibers are assembled in the collector in the form of sheets, clumps or other shapes, said cotton fibers being chemically modified with a poly(MAA-co-EGDMA) layer, said synthetic cannabinoid drugs being MDMB-4en-PINACA, ADB-4en-PINAC.

8. Use of the chemically modified cotton fiber kit for exhaled breath collection according to claim 7 for the trapping of synthetic cannabinoids in exhaled breath, characterized in that, The exhaled breath of experimental animals is first connected in sequence with the air pump, sampling box and collector, and the air pump is used to make the exhaled breath in the sampling box pass through the collector, after collection, the chemically modified cotton fibers in the collector are eluted, the eluent is blown dry in an air-tight manner, redissolved, centrifuged, and the supernatant is injected into UHPLC-MS / MS for detection.

9. Use of the chemically modified cotton fiber kit for exhaled breath collection device according to claim 7 for the trapping of synthetic cannabinoids in exhaled breath, characterized in that, The exhaled breath collection device comprises: ① The air pump comprises at least one outlet, which can be connected to the sampling box through a pipeline; the air pump can continuously output clean air at a constant flow rate. ② The sampling box comprises a cavity, a detachable partition plate attached to the inside of the cavity, a detachable support attached to the bottom of the cavity and sealing covers at both ends of the cavity; the cavity is configured to accommodate the exhaled breath to be tested or to accommodate the experimental animals therein; the sealing cover comprises at least one outlet, which is controlled to open and close by a switch; the sealing cover is provided with an O-ring to ensure the air tightness between the cavity and the sealing cover, iii. The collector comprises two detachable parts which form a chamber by combination, the chamber can place chemically modified cotton fibers and at least temporarily contain or hold gas therein; the two parts each contain an outlet; wherein the one end outlet is connected with the sampling box through a pipeline, and the other end outlet is connected with a one-way valve. iii. The collector comprises two detachable parts which form a chamber by combination, the chamber can place chemically modified cotton fibers and at least temporarily contain or hold gas therein; the two parts each contain an outlet; wherein the one end outlet is connected with the sampling box through a pipeline, and the other end outlet is connected with a one-way valve.

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