A magnetic solid phase extraction enrichment method for detection of antipyretic and analgesic drugs in municipal domestic sewage
Patent Information
- Application Number
- CN202610482466.2
- Authority / Receiving Office
- CN · China
- Patent Type
- Applications(China)
- Current Assignee / Owner
- Filing Date
- 2026-04-13
- Publication Date
- 2026-09-04
AI Technical Summary
然而，不同吸附材料及萃取条件对目标物富集效果影响显著，针对复杂污水基质中解热镇痛药的磁性固相萃取方法仍有待进一步优化和评价
[0041]本发明方法的部分优点
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Abstract
Description
Technical Field
[0001] This invention relates to the field of environmental testing technology, specifically to a method for enriching antipyretic and analgesic drugs in wastewater. Background Technology
[0002] In recent years, the presence of pharmaceuticals and personal care products as an emerging pollutant in the aquatic environment and their potential health risks have received widespread attention. Antipyretic analgesics, due to their large usage and wide application, constitute a significant proportion of daily medications used by residents. Their parent drugs and metabolites can be excreted into domestic sewage systems. Due to the limited removal efficiency of conventional sewage treatment processes, some antipyretic analgesics can be continuously detected in sewage treatment processes and receiving water bodies, thus posing new requirements for aquatic environmental safety and public health risk assessment. Therefore, establishing precise enrichment methods for antipyretic analgesics in sewage is of significant practical importance for aquatic environmental safety control and public health risk assessment.
[0003] Acetaminophen (APAP) and ibuprofen (IBU) are two of the most widely used antipyretic and analgesic drugs in clinical and daily use, and are also common drug residues in wastewater. Previous studies have shown that these drugs, represented by acetaminophen, are mostly present in environmental water samples at trace levels, with residual concentrations typically ranging from ng / L to μg / L. Wastewater samples also contain a large amount of dissolved organic matter, inorganic salts, and other coexisting pollutants, resulting in a complex matrix composition that can easily interfere with the enrichment, separation, and mass spectrometry detection of target analytes. Therefore, before performing liquid chromatography-tandem mass spectrometry (LC-MS / MS) analysis, sample pretreatment is usually necessary to purify, enrich, and concentrate the target analytes, thereby improving the sensitivity and accuracy of detection.
[0004] Currently, pretreatment methods for drug residues in environmental water samples mainly include solid-phase extraction (SPE), solid-phase microextraction (SPE), stir bar adsorption extraction (SPE), and liquid-phase microextraction (LPME). Among these, SPE is widely used due to its good enrichment and purification capabilities, but its practical application still suffers from drawbacks such as cumbersome operation steps, long processing time, and high organic solvent consumption. Magnetic solid-phase extraction (SPE), as an extension of SPE technology, uses magnetic adsorbents as dispersing adsorbents and can rapidly achieve solid-liquid separation under an external magnetic field. It offers advantages such as simple operation, short extraction time, low solvent consumption, and good reproducibility, and has shown promising application prospects in environmental sample pretreatment in recent years. However, different adsorbents and extraction conditions significantly affect the enrichment effect of the target analyte, and magnetic solid-phase extraction methods for antipyretic analgesics in complex wastewater matrices still require further optimization and evaluation.
[0005] This invention establishes a magnetic solid-phase extraction (SPE) enrichment method for antipyretic analgesics in wastewater samples, targeting acetaminophen and ibuprofen. The enriched samples can then be used for quantitative detection. Based on comparisons of different magnetic bead materials, suitable adsorption materials were screened, and key parameters such as sample pH, extraction time, loading volume, and elution conditions were further optimized. Simultaneously, methodological validation was conducted on linear range, precision, limit of detection, and spiked recovery. The aim is to provide a rapid, accurate, and applicable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS / MS) technique for monitoring antipyretic analgesics in wastewater samples with complex matrices. Summary of the Invention
[0006] In a first aspect of the present invention, a method for enriching antipyretic analgesics in wastewater by magnetic solid-phase extraction is provided, characterized by comprising the steps of: (1) Take a wastewater sample, mix it well, let it stand, centrifuge and filter it, adjust the pH to 6.0~9.0, and obtain the sample solution; (2) Add magnetic solid phase extraction material to the sample solution, perform extraction, and then separate the magnetic solid phase extraction material by applying an external magnetic field; (3) Elute the magnetic solid phase extraction material with an eluent and collect the eluent as the test solution; The antipyretic analgesic is selected from the following group: acetaminophen, ibuprofen, or a combination thereof; The magnetic solid phase extraction material is a magnetic bead with a hydrophilic-lipophilic balanced (HLB) surface; The eluent is selected from the group consisting of water, methanol, acetonitrile, or combinations thereof.
[0007] In another preferred embodiment, the pH value of the sample is adjusted to 7.5~8.5 in step (1).
[0008] In another preferred embodiment, the eluent is methanol. In some embodiments, the loading volume of the wastewater sample in step (1) is 0.5 to 2 mL.
[0009] In another preferred embodiment, the loading volume of the wastewater sample is 0.8 to 1.2 mL.
[0010] In some embodiments, the amount of magnetic solid phase extraction material used in step (2) is 10~30 mg / mL of sample solution.
[0011] In another preferred embodiment, the amount of the magnetic solid phase extraction material used is 15~25 mg / mL of sample solution.
[0012] In another preferred embodiment, the extraction time is 1 to 5 minutes.
[0013] In some embodiments, the magnetic solid-phase extraction material has an average diameter of 20-40 µm.
[0014] In another preferred embodiment, the diameter distribution of the magnetic solid phase extraction material is 20-40 µm.
[0015] In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size of 60 to 100 Å.
[0016] In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size of 70-90 Å.
[0017] In some embodiments, step (3) further includes: drying the eluent with nitrogen and reconstituted with solvent to obtain the test solution.
[0018] In another preferred embodiment, the solvent is selected from the group consisting of methanol, acetonitrile, or combinations thereof; preferably methanol.
[0019] In some implementations, the following steps are also included: (4) Quantitatively detect the test solution; The quantitative detection described herein is performed using methods selected from the group consisting of: gas chromatography, liquid chromatography, mass spectrometry, gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, spectrometry, and electrochemical detection.
[0020] In another preferred embodiment, the quantitative detection is performed using liquid chromatography-mass spectrometry.
[0021] In another preferred embodiment, the mass spectrometry conditions are: an electrospray ionization source is used, multiple reaction monitoring (MRM) mode is employed, and the collision gas is argon. Specifically, positive ion mode (ESI+) was used to determine acetaminophen, and negative ion mode (ESI-) was used to determine ibuprofen.
[0022] In some embodiments, step (1) further includes adding a deuterated isotope internal standard to the sample; The deuterated isotope internal standard is selected from the following group: acetaminophen-D3, ibuprofen-D3, or a combination thereof; In another preferred embodiment, the concentration of the deuterated isotope internal standard added is 5~20 μg / L.
[0023] In another preferred embodiment, the concentration of the added deuterated isotope internal standard is 8~12 μg / L.
[0024] In some embodiments, prior to step (2), the magnetic solid-phase extraction material is further activated and equilibrated; The activation is carried out using methanol, and the equilibration is carried out using water.
[0025] In another preferred embodiment, the equilibration is carried out using ultrapure water.
[0026] In some embodiments, the wastewater is domestic sewage or effluent from a sewage treatment plant.
[0027] In a second aspect of the invention, an application of a magnetic solid-phase extraction material for the enrichment of antipyretic and analgesic drugs in wastewater is provided, characterized in that... The magnetic solid-phase extraction material is a magnetic bead with a hydrophilic-lipophilic balanced surface (HLB). The antipyretic analgesics mentioned are selected from the following group: acetaminophen, ibuprofen, or combinations thereof; The enrichment process includes the following steps: (1) taking a wastewater sample, mixing it thoroughly, letting it stand, centrifuging and filtering it, adjusting the pH to 6.0~9.0, and obtaining a sample solution; (2) Add magnetic solid phase extraction material to the sample solution, perform extraction, and then separate the magnetic solid phase extraction material by applying an external magnetic field; (3) Use an eluent to elute the magnetic solid phase extraction material and collect the eluent as the test solution.
[0028] In another preferred embodiment, in step (1), the pH value of the sample is adjusted to 7.5~8.5; In another preferred embodiment, the magnetic solid-phase extraction material has an average diameter of 20-40 µm.
[0029] In another preferred embodiment, the diameter distribution of the magnetic solid phase extraction material is 20-40 µm.
[0030] In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size of 60 to 100 Å.
[0031] In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size of 70-90 Å.
[0032] In another preferred embodiment, step (3) further includes: drying the eluent with nitrogen and reconstituted with a solvent to obtain the test solution, wherein the solvent is selected from the group consisting of methanol, acetonitrile, or a combination thereof.
[0033] It should be understood that, within the scope of this invention, the above-described technical features of this invention and the technical features specifically described below (such as in the embodiments) can be combined with each other to form new or preferred technical solutions. Due to space limitations, they will not be described in detail here. Attached Figure Description
[0034] Figure 1 This is a flowchart of the magnetic solid phase extraction operation of the present invention. Figure 2AThe effect of sample pH on the recovery rates of APAP and IBU was shown. Figure 2B The effects of different solid-phase extraction adsorbents on the recovery rates of APAP and IBU were shown. Figure 2C The effect of the amount of magnetic solid-phase extraction adsorbent on the recovery rates of APAP and IBU was shown. Figure 2D The effect of sample volume on the recovery rates of APAP and IBU was shown. Detailed Implementation
[0035] Through extensive and in-depth research, the inventors discovered a magnetic solid-phase extraction method for enriching acetaminophen and ibuprofen in domestic sewage, and based on this, they completed this invention.
[0036] In UPLC-MS / MS, the response of acetaminophen was relatively stable under different conditions, while the peak shape and response of ibuprofen were more easily affected by pretreatment conditions and mobile phase system, indicating that the two target substances have significant differences in behavior in complex wastewater matrix.
[0037] This difference is closely related to the physicochemical properties of the target analytes. Acetaminophen has a high pKa and exists mainly in the molecular state under the conditions of this study, thus its chromatographic behavior and mass spectrometry response are relatively stable. Ibuprofen, being an acidic drug, has an ionization state that is more sensitive to the pH of the system. Previous studies have shown that different adsorbents and purification levels can affect the ion inhibition / enhancement effects of acidic drugs in wastewater samples. Therefore, ibuprofen exhibits a more pronounced condition dependence in this study, indicating that its detection results are more susceptible to the influence of wastewater coexistences and matrix effects.
[0038] Despite the complex matrix of wastewater samples, magnetic solid-phase extraction (MSE) pretreatment demonstrated good applicability in this study. Compared with conventional column-based SSE, the pretreatment time of this method was reduced by approximately 80%. This method utilizes an external magnetic field to rapidly separate the adsorbent material from the sample solution, simplifying some operational steps. Furthermore, while ensuring good recovery and reproducibility, it effectively enriches the target analytes, providing stable sample pretreatment conditions for subsequent high-performance liquid chromatography-tandem mass spectrometry (HPLC-MS / MS) detection.
[0039] In some implementation methods, the isotope internal standard is involved in the entire sample pretreatment process, which helps to correct for the loss of the target analyte during extraction, elution, concentration and injection, thereby improving the reliability of trace drug determination results in complex wastewater samples.
[0040] The enrichment described in this invention refers to the adsorption of specific substances in a sample onto a magnetic solid-phase extraction material by adding the material. After enrichment, the adsorbed substances can be subjected to operations including but not limited to: elution, drying and reconstitution, and quantitative detection.
[0041] Some advantages of the method of the present invention 1. Compared with conventional column solid phase extraction, the extraction time is reduced by more than 80%.
[0042] 2. Small sample loading volume, low solvent consumption.
[0043] 3. High recovery rate and good repeatability.
[0044] 4. Low detection limit and high sensitivity The technical solution of the present invention is further described below with reference to specific implementation examples. However, the following embodiments do not constitute a limitation of the present invention. All application methods based on the principles and technical means of the present invention are within the scope of the present invention. Experimental methods in the following embodiments that do not specify specific conditions are generally performed under conventional conditions or as recommended by the manufacturer. Unless otherwise stated, percentages and parts are by weight.
[0045] General experimental methods instrument HLB magnetic solid-phase extraction material (20-40 µm; 80 Å, polystyrene matrix, specific surface area 680 m²) 2 / g, Ajabel Biotech), PS magnetic solid-phase extraction material (20-40 µm; 80 Å, polystyrene matrix, specific surface area 680 m²). 2 / g, Ajabel Biotech), MAX Magnetic Solid Phase Extraction Material (20-40 µm; 80 Å, polystyrene matrix, specific surface area 680 m²). 2 / g, Ajaliberty Inc.
[0046] Sample pretreatment Accurately measure 10 mL of wastewater sample, add 10 μL of 10 μg / L internal standard solution, mix thoroughly, and let stand for 30 minutes. Then, centrifuge the sample at 4000 rpm and 4 ℃ for 30 minutes. Filter the supernatant through a 0.45 μm PTFE filter to further remove insoluble particles. Adjust the pH by adding an appropriate amount of 0.1% formic acid aqueous solution, and store at 4 ℃ for later analysis.
[0047] Preparation and activation of magnetic bead suspension Accurately weigh 500.0 mg of magnetic beads into a 15 mL centrifuge tube, add 5 mL of ultrapure water, and shake at a constant speed for 30 s to prepare a magnetic bead suspension. Add 200 μL of the magnetic bead suspension to each sample tube, add 1 mL of methanol, and vortex to ensure that the methanol and target magnetic beads are completely activated. Then place the centrifuge tube on a strong magnet and let it stand for 30 s until the methanol and magnetic beads are completely separated, then discard the methanol. Add 1 mL of pure water to equilibrate, vortex for 30 s, and then discard the supernatant.
[0048] Pour the sample into a centrifuge tube containing activated magnetic beads, vortex for 2 min, then place the centrifuge tube on a strong magnet for 1 min until the magnetic beads are completely adsorbed on one side of the centrifuge tube, and discard the supernatant. Add 1 mL of pure water to the centrifuge tube to rinse the magnetic beads, vortex for 2 min, and discard the supernatant. Add 1 mL of methanol solution, vortex for 2 min to elute the magnetic beads, then place the centrifuge tube on a magnet and collect the eluent. Then blow the eluent to near dryness with nitrogen, add 2 mL of methanol-water solution (1:9, v / v) to reconstitute, filter through a 0.22 μm filter membrane, and analyze by UPLC-MS / MS.
[0049] Chromatographic conditions Chromatographic column: ACQUITY UPLC T3 (100 mm × 2.1 mm, 1.8 μm); column temperature: 35 ℃; flow rate: 0.3 mL / min; injection volume: 5 μL. Mobile phase A: ultrapure water; mobile phase B: methanol. Gradient elution program (volume fraction): 0–4.5 min, 90% A; 4.5 min–5.5 min, 20% A; 5.5–7.0 min, 5% A; 7.0–8.0 min, 90% A; 8.0–10.0 min, 90% A.
[0050] Mass spectrometry conditions Electrospray ionization source; multiple reaction monitoring (MRM) scanning mode; ionization method: acetaminophen is determined as ESI+, ibuprofen as ESI-; capillary voltage: 3.0 kV; ion source temperature: 120 ℃; desolventizing temperature: 350 ℃; cone gas flow: 150 L / Hr; desolventizing gas flow: 650 L / Hr; collision gas: high-purity argon, 99.999%. Table 1. Mass spectrometry parameters of the two drugs and their internal standard Those skilled in the art will understand that the instruments and conditions of each step described above can be optimized and adjusted within the conventional range, as long as the same effect can be achieved without departing from the scope of the present invention.
[0051] Example 1: Screening of sample solution pH The pH of the sample solution was adjusted using 0.1% formic acid aqueous solution and ammonia water. The effect of pH on the magnetic solid-phase extraction efficiency within the range of 3.0–8.0 was systematically investigated. Tests were conducted according to general experimental methods. Figure 2AIt was found that within the pH range investigated in the experiment, the spiked recoveries of the two antipyretic analgesics gradually increased with increasing system pH, reaching their optimum at pH 8.0. In the spiked recovery experiments of the method of this invention, the apparent recoveries of the target analytes in some samples were higher than 100%. Analysis suggests that this result is mainly due to the fact that coexisting organic matter, inorganic salts, and other matrix components in the wastewater samples, after enrichment in pretreatment, jointly enter the detection system and enhance the response to the target analytes. The above phenomenon reflects the apparent quantification being higher under complex matrix conditions, rather than the actual recovery of the target analytes exceeding the theoretical value. Therefore, the closer the apparent recovery rate is to 100%, the smaller the interference received under these conditions, and the more accurate and reliable the measurement results. Overall, the method of this invention still has good enrichment ability and detection stability for the target analytes. The recoveries of the method of this invention in multiple replicate samples are concentrated within a reasonable range and have good repeatability, indicating that the method has good feasibility and stability.
[0052] Example 2: Screening of magnetic solid-phase extraction adsorbents The inventors conducted an initial screening of MAX, HLB, PS, C18, and C8. C8 and C18 were excluded because they exhibited poor dispersibility in aqueous matrices, resulting in weakened adsorption capacity. Ultimately, MAX, HLB, and PS were selected for further screening.
[0053] Three magnetic solid-phase extraction (MSE) materials—HLB, MAX, and PS—were used in a comparative experiment on wastewater samples spiked at a concentration of 20 μg / L. Tests were performed according to standard experimental methods. The results showed that for compound IBU, the recovery rate was 85.9% for samples using PS MSE, 92.0% for samples using MAX MSE, and 99.8% for samples using HLB MSE. For compound APAP, the recovery rate was 109% for samples using PS MSE, 113% for samples using MAX MSE, and 101.7% for samples using HLB MSE.
[0054] Depend on Figure 2B It can be seen that HLB magnetic solid phase extraction material has better extraction efficiency and repeatability for the target analyte than the other two materials.
[0055] Example 3 Screening of the amount of magnetic solid phase extraction materials The amount of magnetic solid-phase extraction (MSPE) material used is a crucial factor affecting its efficiency. At low concentrations, the adsorbent is insufficient to provide enough adsorption sites for the target analyte. As the amount of adsorbent increases, the recovery rate rises, but plateaus after exceeding the optimal concentration, and may even decrease due to aggregation. Testing was conducted using standard experimental methods. As shown in Figure 2C, for a 1 mL sample, the extraction efficiency continuously increased from 5 mg to 40 mg of MSPE material, stabilizing after 20 mg, indicating that adsorption had reached equilibrium. Therefore, this experiment selected 20 mg / mL of sample as the MSPE material concentration.
[0056] Example 4: Optimization of Sample Loading Volume Under the same HLB magnetic solid-phase extraction material and dosage, different sample volumes (1 mL, 2 mL, 5 mL, 10 mL) of wastewater sample matrix spiked solution (c = 20 μg / L) were added to determine the optimal loading volume by comparing the sample extraction efficiencies. Tests were conducted according to general experimental methods. Figure 2D It was found that the extraction efficiency of antipyretic analgesics gradually decreased with increasing sample volume, reaching its optimal value at a sample volume of 1 mL. The recoveries for loading volumes of 1 mL, 2 mL, 5 mL, and 10 mL were 108.5%, 106.6%, 105.9%, and 104.2%, respectively. To balance extraction efficiency with actual pretreatment efficiency and experimental throughput, HLB (20 mg) magnetic solid-phase extraction material was selected for pretreatment of 1 mL water samples.
[0057] Example 5: Optimization of eluent solvent type and volume In addition to optimizing the adsorption process of the target analyte by the adsorbent during magnetic solid-phase extraction, it is also necessary to select a suitable eluent. Testing was conducted according to general experimental methods. The volume of the eluent is a key parameter determining the elution efficiency and enrichment factor; insufficient volume can lead to incomplete elution of the target analyte, while excessive volume will cause dilution of the analyte, thereby reducing the method's sensitivity and quantitative accuracy. The target analyte was eluted using 0.5 mL and 1.0 mL of pure methanol, and 0.5 mL and 1.0 mL of 90% methanol aqueous solution, respectively, and the peak shape and spiked recovery rate under different systems were investigated.
[0058] The results showed that using pure methanol as the elution solvent yielded better peak shapes for the target drug. For compound IBU, the recovery rate was 114.4% under elution with 0.5 mL pure methanol and 112.7% under elution with 1.0 mL pure methanol. For compound APAP, the recovery rate was 114.1% under elution with 0.5 mL pure methanol and 114.0% under elution with 1.0 mL pure methanol, both at good levels. However, the elution recovery rate of ibuprofen with 90% methanol aqueous solution was lower than that with pure methanol. Considering both peak shape and recovery performance, 1.0 mL pure methanol was ultimately selected as the elution solvent.
[0059] To ensure higher extraction efficiency, elution times of 0.5 min, 1 min, and 2 min were evaluated. The results showed that the recoveries of APAP and IBU were highest at 2 min. Therefore, we selected 2 min as the elution time for subsequent experiments. Under this condition, the recovery rate of pure methanol was higher than that of 90% methanol-water solution, indicating that pure methanol has a stronger elution capacity for the target analytes. To further optimize the elution volume, 1.0 mL was selected as the final condition for better extraction efficiency.
[0060] Example 6: Comparison of magnetic bead pretreatment method and conventional extraction method Magnetic adsorbents possess a large specific surface area and numerous available adsorption sites, which facilitates increased contact opportunities with target analytes and enhances enrichment efficiency. Compared to conventional column-based solid-phase extraction (SPE), this method simplifies pretreatment steps, consumes less sample and solvent, and shortens processing time while maintaining recovery and reproducibility. It enables high-throughput sample analysis with low dosage, and sample preparation is simple and rapid. Table 2 compares the UPLC-MS / MS results of wastewater samples purified by magnetic SPE at the same spiking concentration with those purified by conventional SPE. Table 2. Comparative Analysis of Magnetic Solid Phase Extraction and Conventional SPE Purification Methods Example 7: Analysis of Actual Samples Using the method established in this invention, two antipyretic analgesics were tested on wastewater samples from wastewater treatment plants within the jurisdiction. The results showed that the concentration range of acetaminophen was (1.478~11.660) ng / mL, and the concentration range of ibuprofen was (0.456~1.283) ng / mL.
[0061] Example 8: Linearity, Instrument Performance, and Precision of the Standard Curve Using 1, 10, and 100 ng / mL as low, medium, and high concentration points, six consecutive injections were performed at each concentration point within one day to evaluate the intra-day precision of the method. The experiment was repeated for three consecutive days to examine the inter-day precision. Table 3 shows that the relative standard deviations (RSDs) of the intra-day and inter-day precision were 1.04%–4.34% and 1.12%–4.51%, respectively, indicating good linearity. Table 3. Linear parameters and instrument performance parameters of two antipyretic and analgesic drugs Example 9: Method Recovery and Determination of MDL and MQL Six real wastewater samples were selected for spiked recovery experiments at three spiking levels: 1, 10, and 100 µg / L. After spiking, each sample was analyzed using the optimized pretreatment method, and the results were corrected using the background concentration of the unspiked sample. The spiked recoveries at the low, medium, and high concentration levels were calculated. The results are shown in Table 4. Additionally, blank matrix samples were spiked at low concentrations, pretreated with solid-phase extraction, and analyzed in seven parallel runs. The method detection limit (MDL) and method quantitation limit (MQL) were calculated based on the standard deviation of the results. The MDL was found to be 0.028–0.108 µg / L, and the MQL was 0.090–0.344 µg / L. Table 4. Method recovery rate and MDL and MQL Mechanistic analysis of detection effect Acetaminophen has a high pKa and exists primarily in its molecular state under the conditions of this method, thus exhibiting relatively stable chromatographic behavior and mass spectrometry response. Ibuprofen, being an acidic drug, has an ionization state sensitive to the system's pH and is more susceptible to influences from wastewater coexistences and matrix effects (such as ion suppression / enhancement). This method employs magnetic solid-phase extraction combined with a deuterated isotope internal standard. The internal standard participates in the entire pretreatment process, effectively correcting for matrix effects and operational losses, ensuring the reliability of trace drug determination in complex wastewater samples.
[0062] All documents mentioned in this invention are incorporated herein by reference as if each document were individually incorporated by reference. Furthermore, it should be understood that after reading the foregoing teachings of this invention, those skilled in the art can make various alterations or modifications to this invention, and these equivalent forms also fall within the scope defined by the appended claims.
Claims
1. A method for enriching antipyretic analgesics in wastewater by magnetic solid-phase extraction, characterized in that, Including the following steps: (1) Take a wastewater sample and clarify the wastewater sample to obtain a sample solution; (2) Add magnetic solid phase extraction material to the sample solution and extract to obtain a mixture containing antipyretic analgesic-magnetic solid phase extraction material complex; (3) The antipyretic analgesic-magnetic solid phase extraction material complex is separated from the mixture by an external magnetic field; (4) The antipyretic analgesic-magnetic solid phase extraction material complex was eluted with an eluent, and the eluent was collected as the test solution; The antipyretic analgesic is selected from the following group: acetaminophen, ibuprofen, or a combination thereof; The magnetic solid phase extraction material is a magnetic bead with a hydrophilic-lipophilic balanced (HLB) surface; The eluent is selected from the group consisting of water, methanol, acetonitrile, or combinations thereof; In another preferred embodiment, step (1) further includes: if the pH value of the sample solution is not 6.0~9.0, adjusting the pH value of the sample solution to 6.0~9.
0. In another preferred embodiment, step (1) further includes: if the pH value of the sample solution is not 7.5~8.5, adjusting the pH value of the sample solution to 7.5~8.5; In another preferred embodiment, the clarification process described in step (1) includes: centrifuging the wastewater sample and taking the supernatant, and filtering the supernatant; In another preferred embodiment, the filtration is performed using a 0.45 μm filter head; In another preferred embodiment, the eluent is methanol.
2. The method as described in claim 1, characterized in that, The sample loading volume of the wastewater in step (1) is 0.5 to 2 mL; In another preferred embodiment, the loading volume of the wastewater sample is 0.8 to 1.2 mL.
3. The method as described in claim 1, characterized in that, The amount of magnetic solid phase extraction material used in step (2) is 10~30 mg / mL of sample solution; In another preferred embodiment, the amount of the magnetic solid-phase extraction material used is 15~25 mg / mL of sample solution; In another preferred embodiment, the extraction time is 1 to 5 minutes.
4. The method as described in claim 1, characterized in that, The magnetic solid-phase extraction material has an average diameter of 20-40 µm; In another preferred embodiment, the diameter distribution of the magnetic solid-phase extraction material is 20-40 µm; In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size with an average diameter of 60 to 100 Å; In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size with an average diameter of 70 to 90 Å.
5. The method as described in claim 1, characterized in that, Step (4) also includes: drying the eluent with nitrogen and reconstituted it with solvent to obtain the test solution; In another preferred embodiment, the solvent is selected from the group consisting of methanol, acetonitrile, or combinations thereof; preferably methanol.
6. The method as described in claim 1, characterized in that, Prior to step (2), the magnetic solid-phase extraction material is activated and equilibrated; The activation is carried out using methanol, and the equilibration is carried out using water. In another preferred embodiment, the equilibration is carried out using ultrapure water.
7. The method as described in claim 1, characterized in that, The wastewater refers to domestic sewage or effluent from a sewage treatment plant.
8. A method for detecting antipyretic analgesics in wastewater, comprising the steps of: (a) The antipyretic analgesic is treated by the method described in any one of claims 1-7 to obtain the test solution; (b) Quantitatively detect the test solution; The quantitative detection mentioned above is performed using methods selected from the group consisting of: gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry, spectrometry, and electrochemical detection. In another preferred embodiment, the quantitative detection is performed using liquid chromatography-mass spectrometry. In another preferred embodiment, the mass spectrometry conditions are: an electrospray ionization source is used, multiple reaction monitoring (MRM) mode is employed, and the collision gas is argon. in, When measuring acetaminophen, a positive ion mode (ESI+) is used, and when measuring ibuprofen, a negative ion mode (ESI-) is used.
9. The method as described in claim 8, characterized in that, Step (a) also includes adding a deuterated isotope internal standard to the sample; The deuterated isotope internal standard is selected from the following group: acetaminophen-D3, ibuprofen-D3, or a combination thereof; In another preferred embodiment, the concentration of the added deuterated isotope internal standard is 5~20 μg / L; In another preferred embodiment, the concentration of the added deuterated isotope internal standard is 8~12 μg / L.
10. An application of a magnetic solid-phase extraction material in the enrichment of antipyretic and analgesic drugs in wastewater, characterized in that, The magnetic solid phase extraction material is a magnetic bead with a hydrophilic-lipophilic balanced (HLB) surface; The antipyretic analgesics mentioned are selected from the following group: acetaminophen, ibuprofen, or combinations thereof; The enrichment process includes the following steps: (1) taking a wastewater sample, mixing it thoroughly, letting it stand, centrifuging and filtering it, adjusting the pH to 6.0~9.0, and obtaining a sample solution; (2) Add magnetic solid phase extraction material to the sample solution, perform extraction, and then separate the magnetic solid phase extraction material by applying an external magnetic field; (3) Elute the magnetic solid phase extraction material with an eluent and collect the eluent as the test solution; In another preferred embodiment, in step (1), the pH value of the sample is adjusted to 7.5~8.5; In another preferred embodiment, the magnetic solid-phase extraction material has an average diameter of 20-40 µm; In another preferred embodiment, the diameter distribution of the magnetic solid-phase extraction material is 20-40 µm; In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size with an average diameter of 60 to 100 Å; In another preferred embodiment, the magnetic solid-phase extraction material has an average pore size with an average diameter of 70-90 Å; In another preferred embodiment, step (3) further includes: drying the eluent with nitrogen and reconstituted with a solvent to obtain the test solution, wherein the solvent is selected from the group consisting of methanol, acetonitrile, or a combination thereof.