A mixed mode weak cation exchange magnetic solid phase extraction adsorbent and its preparation method and application

Abstract

The present invention discloses a mixed-mode weak cation exchange magnetic solid phase extraction adsorbent and its preparation method and application. The adsorbent is obtained by copolymerizing styrene (ST), divinylbenzene (DVB) and maleic anhydride (MA) on the surface of Fe3O4 microspheres modified with oleic acid, and then subjecting them to mercaptosuccinic acid carboxylation. The preparation method is simple, low-cost and easy to use. It is applied to the field of illegal drug detection and can quickly extract a variety of illegal drugs from wastewater with strong selectivity. There is no need to filter wastewater, which greatly simplifies the pretreatment steps, avoids adsorption losses during the filtration of raw water samples, and improves the sensitivity of the method. The method of the present invention has the characteristics of simple operation, no need for pretreatment equipment, fast extraction speed, strong selectivity, high sensitivity, and reusability, and has strong practicality.

Description

Technical Field

[0001] The invention belongs to the field of illegal drug detection and relates to a novel adsorbent, in particular to a mixed mode weak cation exchange magnetic solid phase extraction adsorbent and a preparation method and application thereof. Background Art

[0002] Since the abuse of illegal drugs seriously threatens public health, family harmony and social stability, the prevention and control of illegal drugs is a major challenge facing the world today. At present, the abuse of illegal drugs presents new characteristics and new problems such as increasingly covert methods of drug use and difficulty in identifying and discovering new psychoactive substances. Therefore, the development of efficient and accurate illegal drug monitoring and analysis methods is of great significance to curb the spread of illegal drugs and maintain social stability and people's safety. In the past two decades, wastewater-based epidemiology (WBE) has been a new method for monitoring illegal drug abuse. This method analyzes the active ingredients and metabolites of urine and feces in wastewater discharged into the urban sewer network. Compared with traditional social epidemiological methods through social surveys, medical records and statistical evaluation of epileptic seizures, WEB has the advantages of short time, low cost and more reliable data.

[0003] However, the matrix of wastewater samples is complex, and the concentration of illegal drugs is usually as low as ng / L level. Therefore, it is necessary to enrich and purify wastewater samples with highly selective and sensitive instruments before analysis. The main conventional method is to use solid phase extraction (SPE) as a pretreatment solution, and then use liquid chromatography-mass spectrometry and other methods to analyze illegal drugs. However, the disadvantages of SPE are time-consuming, expensive consumables, and the need for related equipment. Magnetic solid phase extraction (MSPE) has overcome the shortcomings of traditional solid phase extraction in dealing with complex matrix samples due to its advantages such as simple separation, rapid extraction, reusability and environmental friendliness, and has attracted more and more people's interest. The active functional groups modified on the surface of different MSPE adsorbents determine whether they are high-capacity or selective. At present, the MSPE materials used for detecting illegal drugs in wastewater are all hydrophilic and lipophilic types. They are high-capacity adsorbents and have non-specific interactions with polar compounds. Therefore, these adsorbents are not selective enough, and it is very easy to extract interferences from the matrix during sample extraction. Summary of the invention

[0004] The present invention provides a novel mixed mode weak cation exchange magnetic solid phase extraction adsorbent, which can be used to quickly extract a variety of illegal drugs from wastewater. The present invention also provides a preparation method of the novel mixed mode weak cation exchange magnetic solid phase extraction adsorbent and its application in illegal drug detection.

[0005] The technical solution adopted by the present invention to solve the technical problem is:

[0006] A method for preparing a mixed-mode weak cation exchange magnetic solid phase extraction adsorbent comprises the following steps:

[0007] 1) FeCl 3 6H 2 O is dissolved in ethylene glycol, sodium acetate and polyethylene glycol 4000 are added, heated to dissolve, and the resulting mixture is transferred to a reactor and heated to react; after the reaction is completed, the obtained Fe 3 O 4 The material was placed in oleic acid, heated and stirred for reaction, and then washed repeatedly with water and ethanol several times to obtain OA-Fe 3 O 4 ;

[0008] 2) Dissolve maleic anhydride (MA) in acetonitrile, add divinylbenzene (DVB), styrene (ST) and OA-Fe 3 O 4 After the mixed solution was heated and stirred for reaction, the synthesized magnetic material was collected by an external magnet and repeatedly cleaned with ethanol and acetonitrile to obtain Fe 3 O 4 @poly(ST / DVB / MA);

[0009] 3) Fe 3 O 4 @poly(ST / DVB / MA) was dispersed in acetonitrile, and mercaptosuccinic acid and 2,2-azobis(isobutyronitrile) (AIBN) were added and ultrasonically mixed; the resulting mixture was heated for reaction, cooled and placed in an alkaline aqueous solution for further hydrolysis for 15-20 hours; finally, it was washed with deionized water, dilute hydrochloric acid and deionized water in turn to obtain a mixed mode weak cation exchange magnetic solid phase extraction adsorbent Fe 3 O 4 @poly(ST / DVB / MA-COOH).

[0010] In the above technical solution, further, the FeCl 3 6H 2 The usage ratio of O, ethylene glycol, sodium acetate and polyethylene glycol 4000 is usually 1-3g:60mL:5.4g:1.5g.

[0011] Furthermore, the heating reaction in 1) is usually carried out at 180-240° C. for 12-16 hours, and the heating and stirring reaction is usually carried out at 85° C. for 3-7 hours.

[0012] Furthermore, in the mixed solution of 2), MA, acetonitrile, DVB, ST and OA-Fe 3 O 4The dosage ratio is usually 2.0g:60mL:0.5mL:2mL:0.2g.

[0013] Furthermore, the mixed solution in 2) can be stirred at 70° C. for 5-10 hours, preferably for 8 hours, and then the synthesized product can be collected by an external magnet.

[0014] Furthermore, in said 3) Fe 3 O 4 The usage ratio of @poly(ST / DVB / MA), acetonitrile, mercaptosuccinic acid and 2,2-azobis(isobutyronitrile) (AIBN) is usually 0.5-1.0 g:50 mL:0.8 g:0.03 g.

[0015] Furthermore, in 3), the mixed solution is reacted at 70° C. for 5 hours, and then added to an aqueous alkali solution at 65° C., wherein the aqueous alkali solution is a 0.045 mol / L KOH or NaOH aqueous solution.

[0016] The mixed-mode weak cation exchange magnetic solid phase extraction adsorbent is used for the analysis of illegal drugs in wastewater by first using HCl or NH 3 ·H 2 O etc. adjust the wastewater sample to neutrality (pH=7), then disperse 50mg of the mixed mode weak cation exchange magnetic solid phase extraction adsorbent into 40-400mL of wastewater sample, stir thoroughly for 1 minute, collect the adsorbent with an external magnet, then remove impurities with a detergent, and elute the adsorbed illegal drugs with an eluent, so as to separate the illegal drugs from the wastewater sample. The detergent can usually be methanol MeOH or acetonitrile ACN, preferably ACN; the eluent can be 4% HCOOH / MC (formic acid / dichloromethane), 4% HCOOH / MeOH (formic acid / methanol), 4% TFA / MC (trifluoroacetate / dichloromethane) or 4% TFA / MeOH (trifluoroacetate / methanol), preferably 4% TFA / MeOH; wherein the percentage represents the volume concentration of the component before the slash in the latter component. The beneficial effects of the present invention are:

[0017] The invention provides a novel mixed-mode weak cation exchange magnetic solid phase extraction adsorbent, which has a simple preparation method, low cost and convenient use. It is applied to the field of illegal drug detection, and can quickly extract a variety of illegal drugs from wastewater without filtering the wastewater, greatly simplifying the pretreatment steps. Combined with liquid chromatography-mass spectrometry, it can quantitatively detect a variety of illegal drugs in wastewater, and the extraction recovery rates of 19 illegal drugs are all greater than 80%. Adsorption equilibrium can be reached within 1 minute, and it can be successfully used for the detection of actual wastewater samples. Compared with the prior art, the method of the invention is simple to operate, does not require pretreatment equipment, has a fast extraction speed, and the illegal drugs in the wastewater sample are effectively extracted through the synergistic effects of π-π interaction, hydrophobic interaction, hydrogen bond and electrostatic interaction, and due to the electrostatic interaction, the selectivity of the adsorbent is strong. There is no need to filter the wastewater, avoid adsorption loss during the filtration of the raw water sample, and improve the sensitivity of the method. The adsorbent can be reused and has good repeatability and stability. It can be combined with liquid chromatography-mass spectrometry to be used for the extraction and detection of illegal drugs in wastewater. It has extremely high sensitivity and a detection limit of 0.03-0.67 ng / L, which can fully meet the detection requirements for trace amounts of illegal drugs in wastewater. BRIEF DESCRIPTION OF THE DRAWINGS

[0018] Figure 1 is Fe in Example 1 3 O 4 SEM micrograph (a), EDX image (b), FT-IR spectrum (c), and TGA analysis (d) of @poly(ST / DVB / MA-COOH) sample.

[0019] Figure 2 Optimization of the magnetic solid phase extraction procedure in Example 2: (a) The effect of eluent type on recovery, (b) The effect of detergent on recovery.

[0020] Table 1 shows the corresponding parameters of the internal standard quantitative method in Example 3.

[0021] Table 2 shows the recovery and precision results of the method in Example 3.

[0022] Table 3 is a comparison of the results of the SPE-UHPLC method and the MSPE-UHPLC method in Example 4 for detecting the concentration of illegal drugs in four real wastewater samples.

[0023] Table 4 shows the concentration of illegal drugs in real wastewater samples detected by the MSPE-UHPLC method in Example 4. DETAILED DESCRIPTION

[0024] The technical solution of the present invention is further described in detail below through specific embodiments. It should be understood that the implementation of the present invention is not limited to the following embodiments, and any form of modification and / or change made to the present invention will fall within the protection scope of the present invention.

[0025] The adsorbent of the present invention is prepared by mixing ST, DVB and MA in an oleic acid-modified Fe 3 O 4 The microspheres are copolymerized on their surface and then carboxylated with mercaptosuccinic acid. The adsorbent can be applied to the field of illegal drug detection and can extract a variety of illegal drugs from wastewater in a simple, rapid and sensitive manner. These illegal drugs include but are not limited to common alkaline drugs, all of which can be detected.

[0026] Example 1

[0027] 1) 2.0 g FeCl 3 6H 2 O was dissolved in 60 mL of ethylene glycol. 5.4 g of sodium acetate and 1.5 g of polyethylene glycol 4000 were added to the above solution and dissolved at 60 °C. The mixture was transferred to a reactor and heated at 220 °C for 14 hours. After the reaction was completed, the obtained Fe 3 O 4 The material was placed in a three-necked flask containing 30 mL of oleic acid and stirred at 85 °C for 5 h. It was washed repeatedly with water and ethanol several times to obtain OA-Fe 3 O 4 .

[0028] 2) Dissolve 2.0 g of maleic anhydride (MA) in 60 mL of acetonitrile, then add 0.5 mL of divinylbenzene (DVB), 2 mL of styrene (ST) and 0.2 g of OA-Fe 3 O 4 The mixed solution was stirred at 70 °C for 8 h, and the synthesized magnetic material was collected by an external magnet and cleaned repeatedly with ethanol and acetonitrile to obtain Fe 3 O 4 @poly(ST / DVB / MA).

[0029] 3) Fe 3 O 4 @poly(ST / DVB / MA) was dispersed in 50 mL of acetonitrile. 0.8 g of mercaptosuccinic acid and 0.03 g of 2,2-azobis(isobutyronitrile) (AIBN) were added and ultrasonically mixed. The mixed solution was reacted at 70 °C for 5 hours, and then further hydrolyzed in a 0.045 mol / L KOH aqueous solution at 65 °C for 18 hours. Finally, it was washed with deionized water, dilute hydrochloric acid and deionized water in turn to obtain Fe 3 O 4@poly(ST / DVB / MA-COOH), its SEM micrograph, EDX image, FT-IR spectrum and TGA analysis are as follows Figure 1 shown.

[0030] Example 2

[0031] 1) Select 21 illegal drugs, namely morphine (MOR), 6 Monoacetylmorphine (6-AM), methylenedioxymethamphetamine (MDMA), methylenedioxyimidoamphetamine (MDA), ketamine (KET), norketamine (NKET), methamphetamine (MAMP), amphetamine (AMP), 4-methylcathinone (4-MMC), methcathinone (MMC), cocaine (COC), benzoylcholine (BE), cotinine (COT), codeine (COD), p-methoxymethamphetamine (PMMA), 4-aminophenyl-N-phenethylpiperidine (4-ANPP), methadone (MTD), tramadol (TRA), norfentanyl (NFN), deacetylfentanyl (NAFN), fentanyl (FN). The analyte standards and isotope-labeled internal standards were dissolved in methanol to prepare standard solutions with a concentration of 0.1 mg / L or 1 mg / L. All prepared standard solutions were stored at -40°C for future use.

[0032] 2) First use HCl or NH 3 ·H 2 The thawed wastewater sample was adjusted to neutral (pH = 7), and then 50 mg of the mixed-mode weak cation exchange magnetic solid phase extraction adsorbent prepared in Example 1 was dispersed into 200 mL of the wastewater sample for extracting illegal drugs, and stirred thoroughly for about 1 minute. The adsorbent was then collected with an external magnet and separated from the wastewater sample.

[0033] 3) Transfer the above adsorbent to a 10mL centrifuge tube containing 3mL of methanol or acetonitrile and wash in a vortex mixer for 30s, discard the organic solvent to selectively remove interfering substances. Then, use 4mL (4% HCOOH / MC, 4% HCOOH / MeOH, 4% TFA / MC or 4% TFA / MeOH) to elute the adsorbed target analyte. Collect the eluted solution in a glass tube and blow nitrogen at room temperature. Use 200μL of 0.2% HCOOH / MeOH to re-dissolve the nitrogen-blown sample. After filtering through a 0.22μm organic phase membrane, transfer the sample solution to an automatic injection bottle for UHPLC-MS / MS analysis to investigate the recovery rate of the sample under different experimental conditions, such as Figure 2As shown, it can be seen that the detergent CAN has a better effect, while the eluents 4% HCOOH / MeOH, 4% TFA / MC or 4% TFA / MeOH can achieve good results, among which 4% TFA / MeOH is the best.

[0034] Example 3

[0035] 1) A quantitative method for 19 illegal drugs was established and an isotope internal standard quantitative method was developed. The validation parameters of this method are shown in Table 1. The 19 illegal drugs were morphine (MOR), 6 Monoacetylmorphine (6-AM), methylenedioxymethamphetamine (MDMA), methylenedioxyimidoamphetamine (MDA), ketamine (KET), norketamine (NKET), methamphetamine (MAMP), amphetamine (AMP), 4-methylcathinone (4-MMC), methcathinone (MMC), cocaine (COC), codeine (COD), p-methoxymethamphetamine (PMMA), 4-aminophenyl-N-phenethylpiperidine (4-ANPP), methadone (MTD), tramadol (TRA), norfentanyl (NFN), deacetylfentanyl (NAFN), fentanyl (FN).

[0036] 2) The correlation coefficients of all analytes were higher than 0.9941 within the corresponding linear range. The limits of detection (S / N=3) and limits of quantification (S / N=10) were 0.03-0.67 ng / L and 0.10-2.00 ng / L, respectively. The spike recovery and precision results of the method are shown in Table 2. The spike recovery in Table 2 was in the range of 87.0%-119.6%, and three concentrations were spiked within the linear range: low, medium and high. The intra-day (n=6) and inter-day (n=3) precisions (Table 2) were in the range of 2.2-15.6% and 1.1-17.0%, respectively. These results indicate that the proposed method has satisfactory accuracy and reproducibility. In addition, the method has an extremely high sensitivity (LOD as low as 0.03 ng / L), which is lower than all the methods reported so far. Therefore, the proposed novel mixed-mode weak cation exchange magnetic solid phase extraction adsorbent method can fully meet the detection requirements of trace illegal drugs in wastewater.

[0037] Example 4

[0038] 1) The mixed-mode weak cation exchange magnetic solid phase extraction adsorbent and the established MSPE-UHPLC-MS / MS method were used to detect illegal drugs in 11 real wastewater samples, and the results are shown in Tables 3 and 4. The detection concentration range of MOR, MAMP, KET, MDMA, COC, COD, MTD, TRA and FN was 0.17-75.34 ng / L.

[0039] 2) It was compared with the traditional solid phase extraction (SPE) method (Oasis MCX). A total of 4 wastewater samples were tested and one sample was selected for spike recovery test (Table 3 Sample 4-spiking), and the results are shown in Table 3. The concentrations of analytes detected by MSPE and SPE methods were consistent. In addition, the paired t-test statistical analysis of the concentrations of the analytes found showed p = 0.235> 0.05, indicating that there was no significant difference between the two pretreatment methods. The above results show that the MSPE method has good accuracy and sensitivity.

[0040] Compared with the traditional SPE method, the proposed MSPE method avoids filtering the raw water sample through a 0.45 μm glass fiber filter membrane. In addition, the filter membrane has an adsorption effect on the analyte, and the MSPE method can avoid the adsorption loss of the filter membrane and improve the sensitivity of the method.

[0041] Table 1

[0042]

[0043]

[0044] Table 2

[0045]

[0046]

[0047] Table 3

[0048]

[0049]

[0050] Concentration:ng / L.

[0051] ND: not detected.

[0052] Table 4

[0053]

[0054] Concentration:ng / L.

[0055] ND: not detected.

[0056] The above-described embodiment is only a preferred solution of the present invention and does not limit the present invention in any form. There are other variations and modifications without exceeding the technical solution described in the claims.

Claims

1. Application of a mixed-mode weak cation exchange magnetic solid phase extraction adsorbent in the analysis of illegal drugs in wastewater, characterized in that: First, the pH of the wastewater sample is adjusted to neutral, and then 50 mg of the mixed mode weak cation exchange magnetic solid phase extraction adsorbent is dispersed into 40-400 mL of the wastewater sample, fully stirred for 1 minute, and then the adsorbent is collected by an external magnet, and then, impurities are removed by a detergent, and then the adsorbed illegal drugs are eluted with an eluent, so that the illegal drugs can be separated from the wastewater sample; the preparation method of the mixed mode weak cation exchange magnetic solid phase extraction adsorbent comprises the following steps: 1) Dissolve FeCl3·6H2O in ethylene glycol, add sodium acetate and polyethylene glycol 4000, heat to dissolve, transfer the obtained mixture to a reactor, and heat to react; after the reaction is completed, put the obtained Fe3O4 material into oleic acid, heat and stir to react, and then wash it repeatedly with water and ethanol several times to obtain OA-Fe3O4; 2) Dissolve maleic anhydride MA in acetonitrile, add divinylbenzene DVB, styrene ST and OA-Fe3O4; after heating and stirring the mixed solution for reaction, collect the synthesized magnetic material by an external magnet, and repeatedly clean it with ethanol and acetonitrile to obtain Fe3O4@poly (ST / DVB / MA); 3) Disperse Fe3O4@poly (ST / DVB / MA) in acetonitrile, add mercaptosuccinic acid and 2,2-azobisisobutyronitrile AIBN, and mix by ultrasonication; the dosage ratio of Fe3O4@poly (ST / DVB / MA), acetonitrile, mercaptosuccinic acid and 2,2-azobisisobutyronitrile AIBN is 0.5-1.0 g: 50 mL: 0.8 g: 0.03 g; heat the obtained mixed solution for reaction, cool it down and put it into an alkaline aqueous solution for further hydrolysis for 15-20 hours; finally, wash it with deionized water, dilute hydrochloric acid and deionized water in turn to obtain a mixed mode weak cation exchange magnetic solid phase extraction adsorbent Fe3O4@poly (ST / DVB / MA-COOH); The illegal drugs are morphine, 6 Monoacetylmorphine, methylenedioxymethamphetamine, ketamine, norketamine, methamphetamine, amphetamine, 4-methylcathinone, methcathinone, cocaine, codeine, p-methoxymethamphetamine, 4-aminophenyl-N-phenethylpiperidine, methadone, tramadol, norfentanyl, desacetylfentanyl, or fentanyl.

2. The use of the mixed-mode weak cation exchange magnetic solid phase extraction adsorbent according to claim 1 in the analysis of illegal drugs in wastewater, characterized in that: The dosage ratio of FeCl3·6H2O, ethylene glycol, sodium acetate and polyethylene glycol 4000 in 1) is (1.0-3.0) g: 60 mL: 5.4 g: 1.5 g.

3. The use of the mixed mode weak cation exchange magnetic solid phase extraction adsorbent according to claim 1 in the analysis of illegal drugs in wastewater, characterized in that: The heating reaction in 1) is carried out at 180-240° C. for 12-16 hours, and the heating and stirring reaction is carried out at 85° C. for 3-7 hours.

4. The use of the mixed-mode weak cation exchange magnetic solid phase extraction adsorbent according to claim 1 in the analysis of illegal drugs in wastewater, characterized in that: The dosage ratio of MA, acetonitrile, DVB, ST and OA-Fe3O4 in the mixed solution in 2) is 2.0 g:60 mL:0.5 mL: 2 mL:0.2 g.

5. The use of the mixed mode weak cation exchange magnetic solid phase extraction adsorbent according to claim 1 in the analysis of illegal drugs in wastewater, characterized in that: The mixed solution in 2) was stirred at 70° C. for 5-10 hours, and then the synthesized product was collected by an external magnet.

6. The use of the mixed-mode weak cation exchange magnetic solid phase extraction adsorbent according to claim 1 in the analysis of illegal drugs in wastewater, characterized in that: In the above 3), the mixed solution is reacted at 70° C. for 5 hours, and then added into an aqueous solution of alkali at 65° C., wherein the aqueous solution of alkali is 0.045 mol / L KOH or NaOH aqueous solution.

7. The use of the mixed mode weak cation exchange magnetic solid phase extraction adsorbent according to claim 1 in the analysis of illegal drugs in wastewater, characterized in that: The detergent is methanol or acetonitrile, and the eluent is 4% formic acid / dichloromethane, 4% formic acid / methanol, 4% trifluoroacetate / dichloromethane or 4% trifluoroacetate / methanol, wherein the percentage represents the volume concentration of the component before the slash in the latter component.

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