Magnetic deep-eutectic solvent, preparation method and application thereof, and pretreatment method and quantitative detection method of wastewater containing antidepressant drug

Abstract

The invention belongs to the technical field of chemical analysis and detection, and particularly relates to a magnetic eutectic solvent, a preparation method and application thereof, and a pretreatment method and a quantitative detection method of wastewater containing antidepressant drugs. The magnetic eutectic solvent provided by the invention comprises a hydrogen bond acceptor, a hydrogen bond donor and cobalt chloride, the hydrogen bond acceptor comprises tri-n-octylphosphine oxide; the hydrogen bond donor comprises aniline, acetamide, ethylene glycol, 1, 3-propylene glycol, thymol or L-menthol; the molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is (1-4): (1-3); the molar ratio of the hydrogen bond acceptor to the cobalt chloride is (1-4): 0.5. The magnetic eutectic solvent provided by the invention has the characteristics of simple preparation and environmental friendliness; the extraction process is simple and convenient and separation is easy to realize when the compound is used as an extraction agent to extract the antidepressant in wastewater, the wastewater pretreatment process is remarkably simplified, and an efficient pretreatment method is provided for accurate detection of trace drug residues in a complex matrix.

Description

Technical Field

[0001] This invention belongs to the field of chemical analysis and detection technology, specifically relating to a magnetic eutectic solvent and its preparation method and application, as well as a pretreatment method and quantitative detection method for wastewater containing antidepressants. Background Technology

[0002] Depression is a form of bipolar disorder, characterized by depressed mood, slowed thinking, and reduced speech and movement. It severely disrupts patients' lives and work. Currently, medication is the primary treatment for depression. Based on their chemical structure and mechanism of action, antidepressants (ADs) can be classified into the following types: tricyclic antidepressants (TCAs), monoamine oxidase inhibitors (MAOIs), and selective serotonin reuptake inhibitors (SSRIs). Antidepressants can enter the aquatic environment through human excretion or pharmaceutical wastewater discharge, posing a threat to ecosystems and human health. As an emerging pollutant in the aquatic environment, large amounts of ADs and their metabolites exhibit high environmental persistence; studies have shown that fluoxetine can maintain its structural integrity in lake water for more than 133 days. Although antidepressants are usually present in trace concentrations, ADs can still bioaccumulate in aquatic organisms, ultimately leading to human health problems such as headaches, dizziness, and gastrointestinal disorders. Furthermore, studies have shown that aquatic organisms (ADs) can be harmful to various organisms, such as aquatic plants (microalgae, photosynthetic damage), fish (zebrafish, balance disorder), and aquatic snails (acute snails, reduced egg production). Therefore, developing effective methods to monitor their concentration in environmental samples is extremely important.

[0003] Because the concentration of residual antidepressants in aquatic environments is relatively low, sample pretreatment is necessary before detection and analysis. Currently, liquid-liquid extraction (LLE) and solid-phase extraction (SPE) are used for the extraction of adrenal inhibitors (ADs), but their application is limited by excessive organic solvent consumption and complex enrichment processes. In recent years, liquid-phase microextraction (LPME) and solid-phase microextraction (SPME) have shown great potential as new technologies for the extraction and enrichment of ADs. Compared with SPME, LPME has advantages such as lower cost, less organic solvent consumption, and simpler operation. As a form of LPME, dispersive liquid-liquid microextraction (DLLME) has been applied to the extraction of ADs from various matrices due to its simple operation and high extraction efficiency. However, the extractants used in traditional DLLME extraction processes have a certain degree of toxicity. In recent years, novel extractants have emerged, such as the ionic liquid 1-octyl-3-methylimidazolium hexafluorophosphate, which has been used for the extraction of adrenal antibodies (ADs) from plasma. However, using ionic liquids as extractants increases dispersion and phase separation time, thus prolonging the entire extraction process and reducing efficiency. These limitations highlight the urgent need for the development of novel solvents, which is also the focus of DLLME's research.

[0004] Deep eutectic solvents (DESs) are novel solvents characterized by low toxicity, biodegradability, and low volatility, primarily synthesized through heating and stirring. To date, several DESs have demonstrated good performance in the extraction of adsorption and extraction (ADs), including thymol-ethylene glycol (2:1 molar ratio), choline-4-chlorophenol chloride (1:2 molar ratio), methyl-trichloroammonium bromide-octanol (1:3 molar ratio), and 1-dodecyl-tetrabutylammonium bromide (1:2 molar ratio). However, most DESs require phase separation by centrifugation after dispersion, thus prolonging the overall extraction time. Therefore, developing novel extraction materials that are easy to prepare and simple to separate is of great significance. Summary of the Invention

[0005] In view of this, the present invention provides a magnetic eutectic solvent and its preparation method and application, a pretreatment method and quantitative detection method for wastewater containing antidepressants. When the magnetic eutectic solvent provided by the present invention is used as an extractant, it can efficiently extract trace amounts of antidepressants in wastewater and is easy to separate.

[0006] To address the aforementioned technical problems, this invention provides a magnetic eutectic solvent comprising a hydrogen bond acceptor, a hydrogen bond donor, and cobalt chloride; The hydrogen bond acceptor includes tri-n-octylphosphine; the hydrogen bond donor includes aniline, acetamide, ethylene glycol, 1,3-propanediol, thymol, or L-menthol. The molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is 1~4:1~3; the molar ratio of the hydrogen bond acceptor to cobalt chloride is 1~4:0.5.

[0007] Preferably, the magnetic eutectic solvent is tri-n-octylphosphine oxide, aniline, and cobalt chloride; the molar ratio of tri-n-octylphosphine oxide, aniline, and cobalt chloride is 2:2:0.5.

[0008] This invention also provides a method for preparing the magnetic eutectic solvent described in the above technical solution, comprising the following steps: The magnetic eutectic solvent is obtained by mixing hydrogen bond acceptor, hydrogen bond donor and cobalt chloride; The mixing is carried out under stirring conditions, the stirring temperature is 70~80℃, the stirring speed is 700~1000rpm, and the stirring time is 18~22min.

[0009] 4. The present invention also provides the application of the magnetic eutectic solvent described in the above technical solution or the magnetic eutectic solvent prepared by the preparation method described in the above technical solution as an extractant.

[0010] Preferably, the magnetic eutectic solvent is used as an extractant for the enrichment of antidepressants.

[0011] This invention also provides a pretreatment method for wastewater containing antidepressant drugs, comprising the following steps: The pH of the wastewater is adjusted to 6-10, and the salt concentration is adjusted to 0-25% to obtain conditioned wastewater; The conditioning wastewater and extractant were mixed and vortexed, then allowed to stand. The magnetic eutectic solvent phase was collected to obtain the enriched antidepressant. The extractant is the magnetic eutectic solvent described in the above technical solution or the magnetic eutectic solvent prepared by the preparation method described in the above technical solution.

[0012] Preferably, the antidepressant contained in the wastewater includes one or more of paroxetine, nortriptyline, fluoxetine, and clomipramine; The volume ratio of the conditioning wastewater to the extractant is 190~210:1; The rotational speed of the vortex oscillation is 1000~1200 rpm, and the duration of the vortex oscillation is 20~70 s; The method for collecting the magnetic eutectic solvent phase is to use a microsyringe to collect droplets of the magnetic eutectic solvent phase.

[0013] This invention also provides a method for detecting the content of antidepressants in wastewater, comprising the following steps: Wastewater is pretreated to obtain enriched antidepressant drugs; the pretreatment method is the same as the pretreatment method described in the above technical solution. The enriched antidepressant drug was mixed with a low-viscosity organic solvent to obtain the test solution; The test solution was subjected to high performance liquid chromatography (HPLC) to obtain an HPLC chromatogram. The peak areas of different analytes in the high performance liquid chromatography (HPLC) spectra were substituted into the standard curves of the corresponding analytes to obtain the content of antidepressants in the wastewater.

[0014] Preferably, the low-viscosity organic solvent includes methanol or acetonitrile; The volume ratio of the enriched antidepressant to the low-viscosity organic solvent is 0.8~1.2:1; The high-performance liquid chromatography (HPLC) detection column is a C18 column, and the detector is an ultraviolet detector.

[0015] Preferably, the high-performance liquid chromatography (HPLC) detection includes the following conditions: column temperature: 25~30℃, flow rate: 0.8~1.2 mL·min. -1 Detection wavelength: 210~220nm, injection volume: 10~20μL, mobile phase: mobile phase A is methanol, mobile phase B is 0.1% (w / w) aqueous solution of phosphoric acid, gradient elution program: 0~3min, volume fraction of mobile phase A is 45%; 3~20min, volume fraction of mobile phase A increases linearly from 45% to 52%; 20~40min, volume fraction of mobile phase A increases linearly from 52% to 65%; 40~45min, volume fraction of mobile phase A is 65%.

[0016] This invention provides a magnetic eutectic solvent comprising a hydrogen bond acceptor, a hydrogen bond donor, and cobalt chloride; the hydrogen bond acceptor comprises tri-n-octylphosphine oxide; the hydrogen bond donor comprises aniline, acetamide, ethylene glycol, 1,3-propanediol, thymol, or L-menthol; the molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is 1-4:1-3; the molar ratio of the hydrogen bond acceptor to cobalt chloride is 1-4:0.5. The magnetic eutectic solvent provided by this invention is simple to prepare and environmentally friendly; furthermore, when used as an extractant to extract antidepressant drugs from wastewater, the extraction process is simple and easy to achieve separation, significantly simplifying the wastewater pretreatment process and providing an efficient pretreatment method for the accurate detection of trace drug residues in complex matrices.

[0017] This invention uses a magnetic eutectic solvent as an extractant to enrich and concentrate trace amounts of antidepressants (ADs) in wastewater, followed by high-performance liquid chromatography (HPLC) detection. This improves the detection sensitivity of ADs and enables the simultaneous and rapid detection of multiple ADs. Attached Figure Description

[0018] Figure 1 Infrared spectra of MDES-2 prepared by TOPO, aniline, CoCl2 and Example 2; Figure 2 The magnetization curve of MDES-2 prepared in Example 2 is shown. Figure 3 This is a schematic diagram of the extraction-high performance liquid chromatography (HPLC) detection process; Figure 4 A columnar comparison of the enrichment folds of different antidepressants by extraction with magnetic eutectic solvents prepared for different embodiments; Figure 5 A column chart comparing the enrichment folds of different antidepressants by extraction with different amounts of magnetic eutectic solvent. Figure 6 A bar chart comparing the enrichment folds of different antidepressants obtained by extraction with the magnetic eutectic solvent prepared in Example 2 at different pH values; Figure 7 A bar chart comparing the enrichment folds of different antidepressants obtained by extraction with the magnetic eutectic solvent prepared in Example 2 at different salt concentrations; Figure 8 A bar chart comparing the enrichment folds of different antidepressants obtained by extraction with the magnetic eutectic solvent prepared in Example 2 at different vortex oscillation times; Figure 9 The images show the physical samples after standing and phase separation, obtained by extracting MDES-2 prepared in Example 2 and DES prepared in Comparative Example 1, respectively. The left side shows the result of Comparative Example 1, and the right side shows the result of Example 2. Figure 10 These are liquid chromatograms of high-concentration spiked water samples, medium-concentration spiked water samples, and river water samples. Detailed Implementation

[0019] This invention provides a magnetic eutectic solvent comprising a hydrogen bond acceptor, a hydrogen bond donor, and cobalt chloride; The hydrogen bond acceptor includes tri-n-octylphosphine oxide (TOPO); the hydrogen bond donor includes aniline, acetamide, ethylene glycol, 1,3-propanediol, thymol, or L-menthol.

[0020] In this invention, the molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is 1-4:1-3, specifically 1:1, 2:1, 3:1, 4:1, 2:2, or 2:3; the molar ratio of the hydrogen bond acceptor to cobalt chloride is 1-4:0.5, specifically 1:0.5, 2:0.5, or 3:0.5. In this invention, the purity of the hydrogen bond acceptor (HBA) can be above 98%; the purity of the hydrogen bond donor (HBD) can be above 98%, specifically 99% or 99.5%; and the purity of the cobalt chloride can be above 99.7%. In this invention, the cobalt chloride facilitates self-aggregation of the magnetic eutectic solvent during extraction, promoting phase separation. Simultaneously, the cobalt chloride gives the magnetic eutectic solvent a blue color, facilitating observation of complete phase separation during extraction.

[0021] In this invention, the magnetic eutectic solvent (MDES) can be tri-n-octylphosphine oxide, aniline, and cobalt chloride; the molar ratio of tri-n-octylphosphine oxide, aniline, and cobalt chloride can be 2:2:0.5.

[0022] In this invention, the viscosity of the magnetic eutectic solvent can be 22.8~132 cP, specifically 40.8 cP, 62.4 cP, 70.8 cP, 72 cP, 86.4 cP, 92.4 cP, or 94.8 cP; the density of the magnetic eutectic solvent can be 0.8~0.99 g / cm³. 3 Specifically, it can be expressed as 0.8904 g / cm³. 3 0.9006 g / cm 3 0.9023 g / cm 3 0.9123 g / cm 3 0.917 g / cm 3 0.9189 g / cm 3 0.9255g / cm 3 0.9259 g / cm 3 0.9278 g / cm 3 Or 0.9615 g / cm 3 The thermal decomposition temperature of the magnetic eutectic solvent can be 102~233℃, specifically 105℃, 108℃, 120℃, 135℃, 141℃, 147℃, 152℃, 172℃ or 186℃.

[0023] The magnetic eutectic solvent provided by this invention has low viscosity, low density and paramagnetism; these properties enable it to be uniformly dispersed in the sample solution and achieve spontaneous and rapid phase separation after extraction, agglomerating into single droplets on the sample phase surface.

[0024] This invention also provides a method for preparing the magnetic eutectic solvent described in the above technical solution, comprising the following steps: The magnetic eutectic solvent is obtained by mixing hydrogen bond acceptor, hydrogen bond donor and cobalt chloride.

[0025] In this invention, the mixing is carried out under stirring conditions, the stirring temperature is 70~80℃, specifically 75℃, and the stirring temperature can be provided by a water bath; the stirring speed is 700~1000rpm, specifically 750rpm, 800rpm or 950rpm; the stirring time is 18~22min, specifically 20min.

[0026] In this invention, the stirring process may further include: cooling the stirred system to room temperature to obtain the magnetic eutectic solvent; the room temperature may be 20~35℃ or 25~30℃; this invention does not have any particular limitation on the cooling method, and conventional methods in the art can be used.

[0027] This invention also provides the application of the magnetic eutectic solvent described in the above-described technical solutions or the magnetic eutectic solvent prepared by the preparation method described in the above-described technical solutions as an extractant. In this invention, the magnetic eutectic solvent, when used as an extractant, can be used for the enrichment of antidepressants. In this invention, the magnetic eutectic solvent, when used as an extractant, can be used for the enrichment of weakly polar antidepressants; the weakly polar antidepressants may include one or more of paroxetine, nortriptyline, fluoxetine, and clomipramine, specifically paroxetine, nortriptyline, fluoxetine, and clomipramine.

[0028] This invention also provides a pretreatment method for wastewater containing antidepressant drugs, comprising the following steps: The pH of the wastewater is adjusted to 6-10, and the salt concentration is adjusted to 0-25% to obtain conditioned wastewater; The conditioning wastewater and extractant were mixed and vortexed, then allowed to stand. The magnetic eutectic solvent phase was collected to obtain the enriched antidepressant. The extractant is the magnetic eutectic solvent described in the above technical solution or the magnetic eutectic solvent prepared by the preparation method described in the above technical solution.

[0029] This invention adjusts the pH of wastewater to 6-10 and the salt concentration to 0-25%, resulting in conditioned wastewater. In this invention, the antidepressant in the wastewater can be a weakly polar antidepressant, specifically one or more of paroxetine, nortriptyline, fluoxetine, and clomipramine. The pH of the wastewater is adjusted to 6-10, specifically 7, 8, or 9; the salt concentration is adjusted to 0-25%, specifically 5%, 10%, 15%, or 20%. This invention does not have special requirements for the method of adjusting the pH and salt concentration of the wastewater; conventional methods in the art are acceptable. In the embodiments of this invention, hydrochloric acid and / or sodium hydroxide are used to adjust the pH of the wastewater (specifically hydrochloric acid or sodium hydroxide), and sodium chloride is used to adjust the salt concentration.

[0030] After obtaining the conditioning wastewater, the present invention mixes the conditioning wastewater and the extractant, vortexes them, and then allows them to stand. The magnetic eutectic solvent phase is collected to obtain the enriched antidepressant drug. In the present invention, the volume ratio of the conditioning wastewater to the extractant can be 190~210:1, specifically 200:1.

[0031] In this invention, the rotational speed of the vortex oscillation can be 1000~1200 rpm, specifically 1000 rpm or 1100 rpm; the duration of the vortex oscillation can be 20~70s, specifically 30s, 40s, 50s or 60s.

[0032] The pretreatment method provided by this invention can enrich antidepressant drugs by 185 to 238 times.

[0033] This invention does not have specific requirements for the settling time, as long as it allows for effective separation of the aqueous phase and the magnetic eutectic solvent phase; in the embodiments of this invention, the settling time is 1 minute. This invention utilizes the low viscosity, paramagnetism, hydrophobicity, and lower density (less than water) of the magnetic eutectic solvent. After vortexing and settling, the solvent self-aggregates on the sample phase surface to form droplets, achieving rapid phase separation without centrifugation, thereby constructing a vortex-assisted dispersion liquid-liquid microextraction system.

[0034] In this invention, the method for collecting the magnetic eutectic solvent phase can be to use a microsyringe to collect droplets of the magnetic eutectic solvent phase.

[0035] This invention also provides a method for detecting the content of antidepressants in wastewater, comprising the following steps: Wastewater is pretreated to obtain enriched antidepressant drugs; the pretreatment method is the same as the pretreatment method described in the above technical solution. The enriched antidepressant drug was mixed with a low-viscosity organic solvent to obtain the test solution; The test solution was subjected to high performance liquid chromatography (HPLC) to obtain an HPLC chromatogram. The peak areas of different analytes in the high performance liquid chromatography (HPLC) spectra were substituted into the standard curves of the corresponding analytes to obtain the content of antidepressants in the wastewater.

[0036] This invention involves pretreatment of wastewater to obtain enriched antidepressant drugs. In this invention, the antidepressant in the wastewater can be a hydrophobic antidepressant, specifically one or more of paroxetine, nortriptyline, fluoxetine, and clomipramine. The pretreatment method described above enables efficient enrichment and separation of antidepressant drugs from wastewater, improving the accuracy of subsequent quantitative detection.

[0037] After obtaining the enriched antidepressant, the present invention mixes the enriched antidepressant with a low-viscosity organic solvent to obtain a test solution. In the present invention, the low-viscosity organic solvent includes methanol or acetonitrile; the volume ratio of the enriched antidepressant to the low-viscosity organic solvent can be 0.8~1.2:1, specifically 1:1.

[0038] After obtaining the test solution, the present invention performs high-performance liquid chromatography (HPLC) on the test solution to obtain an HPLC chromatogram. In the present invention, the HPLC column used for detection can be a C18 column, and the C18 column can be a ZORBAX Eclipse XDB-C18 column (250mm × 4.6mm, 5μm); the detector used for HPLC detection can be an ultraviolet detector.

[0039] In this invention, the high-performance liquid chromatography (HPLC) detection may include the following conditions: column temperature: 25~30℃, flow rate: 0.8~1.2 mL·min -1 Detection wavelength: 210~220nm, injection volume: 10~20μL, mobile phase: mobile phase A is methanol, mobile phase B is 0.1% (w / w) aqueous solution of phosphoric acid, gradient elution program: 0~3min, volume fraction of mobile phase A is 45%; 3~20min, volume fraction of mobile phase A increases linearly from 45% to 52%; 20~40min, volume fraction of mobile phase A increases linearly from 52% to 65%; 40~45min, volume fraction of mobile phase A is 65%.

[0040] After obtaining the high-performance liquid chromatography (HPLC) chromatograms, this invention substitutes the peak areas of different analytes in the HPLC chromatograms into the corresponding standard curves of the analytes to obtain the content of antidepressants in the wastewater. This invention obtains the standard curves according to conventional methods in the art. In this invention, the analyte can be a specific antidepressant.

[0041] The linear range of the detection method provided by this invention is as follows: paroxetine, fluoxetine, and clomipramine are 0.0003~0.5 μg / mL, and nortriptyline is 0.0005~1 μg / mL; the correlation coefficient of the detection method is greater than 0.9994; the limit of detection is 0.0001~0.0002 μg / mL, and the limit of quantitation is 0.0003~0.0005 μg / mL; the relative standard deviations of intra-day and inter-day precision are 0.7~5.7% and 0.3~7.4%, respectively; the recoveries of paroxetine, nortriptyline, fluoxetine, and clomipramine in river water and tap water are 90.9~113.7% and 91.4~108.6%, respectively.

[0042] The simplicity of the detection method provided by this invention lies in the easy synthesis of the extractant (20 min) and the rapid extraction process (50 s). The detection method provided by this invention exhibits low limits of detection and quantitation, high sensitivity, high extraction efficiency, and good linearity, precision, and accuracy. The MDES-based vortex-assisted dispersion liquid-liquid microextraction (VA-MDES-DLLME) pretreatment method in this invention is not only a simple, low-cost, and rapid sample pretreatment procedure, but also an excellent enrichment scheme for trace target analytes in aqueous matrices.

[0043] To further illustrate the present invention, the technical solutions provided by the present invention will be described in detail below with reference to the embodiments, but they should not be construed as limiting the scope of protection of the present invention.

[0044] The materials and instruments used in the examples are shown below: Nortriptyline, purity ≥97%, was purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Clomipramine, purity ≥97%, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Paroxetine, purity ≥97%, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Fluoxetine, purity ≥97%, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Tri-n-octylphosphine oxide, 98% purity, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Thymol, 98% purity, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. 1,3-Propanediol, 98% purity, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Ethylene glycol, 98% purity, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Cobalt chloride (CoCl2), 99.7% purity, was purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Aniline, 99.5% purity, was purchased from Shanghai Maclean Biochemical Technology Co., Ltd. L-Menthol, 99.5% purity, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Acetamide, 99% purity, purchased from Shanghai Maclean Biochemical Technology Co., Ltd. Sodium chloride (NaCl), analytical grade, purchased from Tianjin Guangfu Technology Co., Ltd. Sodium hydroxide, analytical grade, purchased from Tianjin Kemeo Chemical Reagent Co., Ltd. Hydrochloric acid, analytical grade, purchased from Tianjin Guangfu Technology Co., Ltd. Phosphoric acid, HPLC grade, purchased from Tianjin Damao Chemical Reagent Factory; Methanol, HPLC grade, purchased from Tianjin Kemeo Chemical Reagent Co., Ltd. Vortex hybrid oscillator, serial number 92-12-536, Shanghai Medical University Instrument Factory; High performance liquid chromatograph, Shimadzu LC-2030 Plus, Japan; Fourier transform infrared spectrometer, Thermo Fisher Scientific, USA, Nicoleti S5; MS-H280-Pro Digital Display Heating Magnetic Stirrer, Dalongxingchuang Experimental Instruments Co., Ltd.; ZCT-B Integrated Thermal Analyzer, Beijing Jingyi High-Tech Instruments Co., Ltd. DV3TL rotational viscometer, Brookfield, USA; DM40 density meter, Mettler Toledo, Switzerland; Vibrating sample magnetometer, Lake Shore, USA, Model 7404.

[0045] Example 1 Tri-n-octylphosphine oxide (TOPO), acetamide, and cobalt chloride were mixed in a molar ratio of 2:2:0.5 and magnetically stirred for 20 min at 70°C (water bath) and 1000 rpm, then cooled to room temperature (25°C). A deep blue magnetic eutectic solvent, denoted as MDES-1, was obtained.

[0046] Examples 2-11 The magnetic eutectic solvent was prepared according to the method in Example 1. The types and proportions of materials are shown in Table 1.

[0047] Table 1. Types and proportions of materials used in the preparation of magnetic eutectic solvents in Examples 1-11

[0048] The viscosity and density of the magnetic eutectic solvents prepared in Examples 1-11 were measured using a DV3TL rotational viscometer and a DM40 densitometer, respectively, and the results are listed in Table 2.

[0049] The thermal stability of magnetic eutectic solvents is determined by their thermal decomposition temperature. T d The evaluation is performed by taking the intersection of the baseline and the extended line of the descending segment of the thermogravimetric curve (obtained using a ZCT-B type integrated thermal analyzer); thermogravimetric experiments were conducted on the magnetic eutectic solvents prepared in Examples 1-11 to obtain thermogravimetric curves, and then the thermal decomposition temperature was obtained. T d The results are listed in Table 2.

[0050] Table 2. Physicochemical properties of magnetic eutectic solvents prepared in Examples 1-11

[0051] As shown in Table 2, the density of MDESs at room temperature ranges from 0.8904 to 0.9615 g / cm³. 3 This indicates that MDESs have a lower density than water, can float on the water surface, and are easy to collect after extraction. Furthermore, by comparing Examples 1, 7-11, it was found that the density of MDESs composed of TOPO, aniline, and CoCl2 decreases with increasing TOPO content.

[0052] In DLLME extraction systems, using low-viscosity extractants not only simplifies sample loading and collection but also promotes uniform dispersion in the sample solution, thereby improving extraction efficiency. However, excessively low extractant viscosity may increase the difficulty of phase separation. The MDESs provided in this invention have a viscosity between 22.8 and 132.0 cP, exhibiting good flowability at room temperature. Experimental results show that increasing the proportion of TOPO can reduce the viscosity of MDESs.

[0053] As can be seen from the results in Table 2, the MDESs provided by this invention... T d The range of 105℃ to 233℃ indicates that it has good thermal stability at room temperature; T d The value increases as the proportion of TOPO increases.

[0054] The TOPO-aniline-CoCl2 (molar ratio 2:2:0.5) MDES-2 prepared in Example 2, as well as TOPO, aniline, and CoCl2, were characterized by FTIR. The resulting infrared spectra are shown below. Figure 1 As shown. By Figure 1 It can be seen that the peak of the P=O bond is from 1148 cm⁻¹-1 (TOPO) moved to 1146cm -1 (MDES) The peak shape broadened and weakened, indicating that the O atoms in TOPO may interact with the Co atoms in CoCl2. 2+ Coordinate bonds are formed. Simultaneously, the stretching vibration peak of the Co-Cl bond (1595 cm⁻¹) is observed. -1 CoCl2) in MDES (1597cm) -1 The shift and weakening of the NH stretching vibration peak of aniline at 3341 cm⁻¹ further confirm the above phenomenon. Furthermore, the peak of the NH stretching vibration of aniline was observed to have shifted from 3341 cm⁻¹. -1 (Aniline) moves to a higher wavenumber of 3344 cm⁻¹ -1 (MDES), indicating the formation of hydrogen bonds. These results demonstrate the successful synthesis of TOPO-aniline-CoCl2 (molar ratio 2:2:0.5)MDES-2.

[0055] The magnetic susceptibility of TOPO-aniline-CoCl2 (molar ratio 2:2:0.5) MDES-2 prepared in Example 2 was determined using a vibrating sample magnetometer (VSM). The resulting magnetization curve is shown below. Figure 2 As shown. By Figure 2 As shown, the magnetic moment is directly proportional to the applied magnetic field. The slope of the linear relationship obtained from regression analysis represents the magnetic susceptibility, which is 3.19 × 10⁻⁶. -6 emu / goe. This result indicates that MDES is paramagnetic.

[0056] Example 12 Reference solution: Nortriptyline, fluoxetine, paroxetine, and clomipramine reference standards (accurately weighed using a 0.01 g balance) were placed in four beakers respectively, dissolved in methanol, and quantitatively transferred to 25 mL volumetric flasks. The solutions were diluted to the mark with methanol, shaken well, and stock solutions of the four ADs were prepared with a concentration of 1 mg / mL. The solutions were stored at 4 °C in the dark for later use.

[0057] Accurately transfer 2 mL of each of the reference standard stock solutions into four separate 10 mL volumetric flasks. Dilute to the mark with methanol and mix well to prepare four intermediate concentration reference solutions of 200 μg / mL. Store at 4°C protected from light. Accurately transfer 1 mL of each of the four intermediate concentration reference solutions into the same 10 mL volumetric flask. Dilute to the mark with methanol and mix well to prepare a mixed reference solution of ADs with any given concentration of 20 μg / mL. This solution should be prepared and used immediately.

[0058] The pH of 10 mL of sample solution (ADs mixed reference solution) was adjusted to 10 and the salt concentration was adjusted to 20% using sodium hydroxide, hydrochloric acid and sodium chloride. Then, 50 μL of the magnetic eutectic solvent prepared in Examples 1-11 was added to the sample solution. After vortexing at 1000 rpm for 50 s and standing for 1 min, the MDES phase aggregated into small droplets on the surface of the sample solution. The droplets were collected using a microsyringe and transferred to a 1.5 mL centrifuge tube to obtain the enriched antidepressant drugs.

[0059] The enriched antidepressant drug was diluted with an equal volume of methanol and then injected for high-performance liquid chromatography (HPLC) detection. The HPLC conditions were as follows: column: ZORBAX Eclipse XDB-C18 column (250 mm × 4.6 mm, 5 μm, Agilent Technologies); column temperature: 30℃; flow rate: 1.0 mL / min. -1 Detection wavelength: 220 nm; injection volume: 10 μL; mobile phase: mobile phase A was methanol, mobile phase B was a 0.1% (w / w) aqueous solution of phosphoric acid; gradient elution program: 0–3 min, mobile phase A volume fraction 45%; 3–20 min, mobile phase A volume fraction linearly increased from 45% to 52%; 20–40 min, mobile phase A volume fraction linearly increased from 52% to 65%; 40–45 min, mobile phase A volume fraction 65%. All experiments were performed in triplicate and the average value was taken.

[0060] Figure 3 This is a schematic diagram of the extraction-high performance liquid chromatography (HPLC) detection process.

[0061] The enrichment factor of the extraction performed in Example 12 was calculated according to Equation 1, and the results are listed in Table 3: Formula 1; in C e This indicates the concentration of the analyte in the enriched antidepressant. C d This indicates the concentration of the analyte in the sample being tested. m e This represents the slope of the standard curve obtained by high-performance liquid chromatography (HPLC) analysis of the extracted sample. m d This represents the slope of the standard curve obtained by high-performance liquid chromatography (HPLC) analysis of the sample before extraction.

[0062] Table 3. Enrichment factors of extraction using magnetic eutectic solvents prepared in Examples 1-11

[0063] Based on Table 3, a bar chart comparing the enrichment folds of different antidepressants obtained by extraction with magnetic eutectic solvents prepared in different embodiments was plotted. Figure 4 As shown. (Combined with Table 3 and...) Figure 4 As can be seen from A, the enrichment factor of (MDES-2) when aniline is used as a hydrogen bond donor (HBD) is ( EF The highest viscosity was observed in MDES-2. This phenomenon is due to the benzene ring structure in aniline, where the π-electron cloud can interact with the aromatic ring of the target analyte via π-π interactions. Furthermore, the amino and nitrogen atoms in aniline allow it to act as both HBD and HBA, promoting hydrogen bonding with ADs and significantly enhancing the binding capacity of the extractant. Therefore, the combined effect of π-π interactions and hydrogen bonding enables MDES-2 to effectively bind to ADs, resulting in high extraction efficiency. In addition, MDES-2 exhibits the lowest viscosity among the six MDESs, which contributes to better dispersion in sample solutions and efficient mass transfer between the two phases.

[0064] Combined with Table 3 and Figure 4 As shown in Figure B, the extraction effect on the target analyte (antidepressant) was best when the molar ratio of TOPO-aniline-CoCl2MDES was 2:2:0.5. An appropriate TOPO / aniline ratio promoted an ordered and stable hydrogen bond network, thereby enhancing the stability of MDES. Conversely, an excess of TOPO or aniline led to over-binding of active sites, reducing the sites available for interaction with ADs and thus decreasing extraction efficiency. Furthermore, MDES synthesized at molar ratios of 2:2:1 and 2:2:1.5 were found to be solid at room temperature, making extraction impossible. The addition of CoCl2 gave MDES a deep blue color, facilitating identification and separation, and also provided weak magnetism, aiding in phase separation and making the extraction process more convenient.

[0065] Example 13 The antidepressant was extracted and enriched according to the method of Example 12 to obtain enriched antidepressant. The difference was that the magnetic eutectic solvent (MDES) added was MDES-2 prepared in Example 2, and the volume of the magnetic eutectic solvent added was adjusted from 50 μL to 60 μL, 70 μL, 80 μL and 90 μL.

[0066] The enriched antidepressant drugs were detected by high-performance liquid chromatography according to the method in Example 12.

[0067] The enrichment factor of the extraction performed in Example 13 was calculated according to Equation 1, and the results are listed in Table 4.

[0068] Table 4. Enrichment factors of extraction using the magnetic eutectic solvent prepared in Example 2 at different addition amounts

[0069] Based on Table 4, a bar chart comparing the enrichment folds of different antidepressants obtained by extraction using different amounts of magnetic eutectic solvent was plotted. Figure 5 As shown. (Combined with Table 4 and...) Figure 5 As can be seen, the extraction efficiency gradually decreases with increasing extractant volume. When the extractant volume is 50 µL, EF The highest level of MDES is achieved when the volume is below 50 μL, making collection difficult and resulting in insufficient volume for HPLC analysis.

[0070] Example 14 The antidepressant was extracted and enriched according to the method of Example 12 to obtain the enriched antidepressant. The difference was that the magnetic eutectic solvent (MDES) was MDES-2 prepared in Example 2, and the pH values ​​of the sample solutions were adjusted to 6, 7, 8, and 9, respectively.

[0071] The enriched antidepressant drugs were detected by high-performance liquid chromatography according to the method in Example 12.

[0072] The enrichment factor of the extraction performed in Example 14 was calculated according to Equation 1, and the results are listed in Table 5.

[0073] Table 5. Enrichment factors of the magnetic eutectic solvent prepared in Example 2 at different pH values ​​during extraction.

[0074] Table 5 shows a bar chart comparing the enrichment folds of different antidepressants extracted using the magnetic eutectic solvent prepared in Example 2 at different pH values. Figure 6 As shown. (Combined with Table 5 and...) Figure 6 It can be seen that when the pH value of the sample solution is 10, the target analyte... EF Maximum. In this invention, when pH < 9, the target analyte exists in cationic form and has high water solubility, hindering its transfer to the extraction phase, leading to... EF The pH decreases. Conversely, when the solution pH is 10, the analyte exists mainly in molecular form and can interact with MDES through π-π interactions, hydrogen bonds, and hydrophobic effects. In this invention, when pH > 10, after vortex vibration, MDES will become a pale blue flocculent dispersed in the sample solution, thus affecting the detection results.

[0075] Example 15 The antidepressant was extracted and enriched according to the method of Example 12 to obtain the enriched antidepressant. The difference was that the magnetic eutectic solvent (MDES) was MDES-2 prepared in Example 2, and the salt concentration values ​​of the sample solution were adjusted to 0, 5%, 10%, 15%, and 25%.

[0076] The enriched antidepressant drugs were detected by high-performance liquid chromatography according to the method in Example 12.

[0077] The enrichment factor of the extraction performed in Example 15 was calculated according to Equation 1, and the results are listed in Table 6.

[0078] Table 6. Enrichment factors of the magnetic eutectic solvent prepared in Example 2 at different salt concentrations during extraction.

[0079] Table 6 shows a bar chart comparing the enrichment folds of different antidepressants extracted using the magnetic eutectic solvent prepared in Example 2 at different salt concentrations. Figure 7 As shown. (Combined with Table 6 and...) Figure 7 It can be seen that the extraction effect on the target analyte is best when the salt concentration of the sample solution is 20%.

[0080] Example 16 The antidepressant was extracted and enriched according to the method of Example 12 to obtain the enriched antidepressant. The difference was that the magnetic eutectic solvent (MDES) was MDES-2 prepared in Example 2, and the vortex oscillation time was adjusted to 20s, 30s, 40s, 60s, and 70s.

[0081] The enriched antidepressant drugs were detected by high-performance liquid chromatography according to the method in Example 12.

[0082] The enrichment factor of the extraction performed in Example 16 was calculated according to Equation 1, and the results are listed in Table 7.

[0083] Table 7. Enrichment factor of MDES-2 prepared in Example 2 extracted at different vortex oscillation times.

[0084] Table 7 shows a bar chart comparing the enrichment folds of different antidepressants extracted using the magnetic eutectic solvent prepared in Example 2 at different vortex oscillation times. Figure 8 As shown. (Combined with Table 7 and...) Figure 8 It can be seen that when the extraction time is between 20-50 seconds, EF The extraction efficiency initially increases and then decreases with increasing vortex oscillation time, with the best extraction effect on the target analyte achieved when the vortex oscillation time is 50 s. In this invention, when the vortex oscillation time exceeds 50 s, the prolonged vortexing leads to excessive dispersion of MDES, thereby reducing the extraction efficiency.

[0085] Comparative Example 1 The eutectic solvent was prepared according to the method in Example 2, except that cobalt chloride was not added during the preparation process. The specific preparation process is as follows: Tri-n-octylphosphine oxide (TOPO) and aniline were mixed in a 1:1 molar ratio and magnetically stirred for 20 min at 70 °C (water bath) and 1000 rpm. After cooling to room temperature (25 °C), a eutectic solvent, denoted as DES, was obtained.

[0086] The ADs mixed reference solution in Example 12 was extracted using MDES-2 prepared in Example 2 and DES prepared in Comparative Example 1, respectively. The pH of 10 mL of sample solution (ADs mixed reference solution in Example 12) was adjusted to 10 and the salt concentration was adjusted to 20% using sodium hydroxide, hydrochloric acid and sodium chloride. Then, 50 μL of extractant was added to the sample solution, and the mixture was vortexed at 1000 rpm for 50 s and allowed to stand for 1 min for phase separation.

[0087] Figure 9 These are images of the extractant after standing and phase separation. The left image shows the extractant of Comparative Example 1 after standing and phase separation, and the right image shows the extractant of Example 2 after standing and phase separation. Figure 9 It can be seen that the amount of extractant phase (DES) on the left side of the liquid surface is less, and the aqueous phase is more turbid, while the extractant phase (MDES) on the right side is more completely aggregated, and the aqueous phase is clearer; this indicates that cobalt chloride is conducive to the self-aggregation of magnetic eutectic solvents during the extraction process, which is beneficial to phase separation.

[0088] Test Example 1 1. Detection of linearity, limit of detection, and limit of quantitation. Accurately measure an appropriate amount of the ADs mixed reference solution from Example 12, and prepare a series of mixed reference solutions with varying concentration gradients through serial dilution; specifically, the concentrations of paroxetine, fluoxetine, and clomipramine are 0.0003, 0.0005, 0.001, 0.0025, 0.005, 0.01, 0.025, 0.05, 0.1, 0.25, and 0.5 μg / mL, respectively; the concentrations of nortriptyline are 0.0005, 0.001, 0.002, 0.005, 0.01, 0.02, 0.05, 0.1, 0.2, 0.5, and 1 μg / mL, respectively. Extraction was performed using MDES-2 as the extractant according to the method of Example 12, and HPLC analysis was performed according to the method of Example 12. The x-axis and y-axis are set as the concentrations of the analytes (…). X ) and peak area ( Y Select 1 / X As a weighting factor, Y right XWeighted linear regression was performed. The limit of detection (LOD) and limit of quantitation (LOQ) were defined as the analyte concentrations at which the signal-to-noise ratio (S / N) of the target analyte reached 3 and 10, respectively. The results are listed in Table 8.

[0089] Table 8. Regression equations and other efficacy indicators for determining four antidepressants.

[0090] Table 8 shows that the linear ranges for paroxetine, fluoxetine, and nortriptyline were between 0.0003 and 0.5 μg / mL, while that for nortriptyline was between 0.0005 and 1 μg / mL. All had correlation coefficients greater than 0.9994, indicating good linearity. The LOD and LOQ ranged from 0.0001 to 0.0002 μg / mL and 0.0003 to 0.0005 μg / mL, respectively. The four adrenal inhibitors (ADs) showed... EF Between 185 and 238.

[0091] 2. Precision testing Accurately measure an appropriate amount of the ADs mixed reference solution from Example 12 and prepare a series of mixed reference solutions with varying concentration gradients through serial dilution; specifically: the concentrations of paroxetine, fluoxetine, and clomipramine are 0.0005, 0.005, 0.05, and 0.5 μg / mL, respectively; the concentrations of nortriptyline are 0.001, 0.01, 0.02, 0.1, and 1 μg / mL, respectively. Extraction was performed using MDES-2 as the extractant according to the method of Example 12, and HPLC analysis was performed according to the method of Example 12.

[0092] The precision was evaluated by calculating the relative standard deviation (RSD), including intra-day precision and inter-day precision. Intra-day precision was calculated by performing three parallel extractions and measurements on samples of the same concentration level within the same day; inter-day precision was calculated by performing extractions and measurements on three consecutive days. The results are listed in Tables 9 and 10.

[0093] Table 9. Results of intraday precision determination for four antidepressants ( n =3)

[0094] Table 10 Results of daytime precision determination for four antidepressants ( n =3)

[0095] The intra-day and inter-day precision RSDs of the detection method provided by this invention are between 0.7% and 5.7% and 0.3% and 7.4%, respectively, indicating that the method has good precision.

[0096] 3. Accuracy Test The accuracy of this method was evaluated using the recovery rate. River water and tap water samples were used as actual water samples. The river water sample was collected from the Fen River in Taiyuan City, and the tap water sample was collected from Shanxi Medical University in Jinzhong City. The water samples were filtered through a 0.22 μm microporous membrane and then stored at 4°C in the dark for later use.

[0097] The ADs mixed reference solution prepared in Example 12 was added to the water samples to obtain spiked water samples of different concentrations. The concentrations of paroxetine, fluoxetine, and clomipramine in the spiked water samples were 0.005 μg / mL (low-concentration spiked sample), 0.05 μg / mL (medium-concentration spiked sample), and 0.5 μg / mL (high-concentration spiked sample), respectively; the concentrations of nortriptyline were 0.01 μg / mL (low-concentration spiked sample), 0.1 μg / mL (medium-concentration spiked sample), and 1 μg / mL (high-concentration spiked sample), respectively. Following the method of Example 12, MDES-2 was used as the extractant to extract river water samples, tap water samples, and spiked water samples of different concentrations, respectively. HPLC analysis was performed according to the method of Example 12, with each concentration analyzed in triplicate. The recovery rate was calculated according to Equation 2, and the results are listed in Table 11. Recovery rate (%) ×100 Equation 2.

[0098] No four ADs were detected in either river water or tap water samples. The liquid chromatography spectra of the high-concentration spiked water sample, the medium-concentration spiked water sample, and the river water sample are shown below. Figure 10 As shown, 1 is paroxetine, 2 is nortriptyline, 3 is fluoxetine, and 4 is clomipramine.

[0099] Table 11 Recovery rate of antidepressants in environmental water samples ( n =3) As shown in Table 11, the recovery rates and RSDs of the four ADs in environmental water were between 90.9% and 113.7% and 1.7% and 8.0%, respectively, indicating that the method has good accuracy.

[0100] Combine Table 11 and Figure 10 As can be seen, the detection method provided by this invention has been successfully applied to real samples.

[0101] Although the above embodiments have provided a detailed description of the present invention, they are only some embodiments of the present invention, and not all embodiments. People can obtain other embodiments based on these embodiments without creative effort, and these embodiments all fall within the protection scope of the present invention.

Claims

1. A magnetic eutectic solvent, characterized in that, Including hydrogen bond acceptors, hydrogen bond donors, and cobalt chloride; The hydrogen bond acceptor includes tri-n-octylphosphine; the hydrogen bond donor includes aniline, acetamide, ethylene glycol, 1,3-propanediol, thymol, or L-menthol. The molar ratio of the hydrogen bond acceptor to the hydrogen bond donor is 1~4:1~3; the molar ratio of the hydrogen bond acceptor to cobalt chloride is 1~4:0.

5.

2. The magnetic eutectic solvent according to claim 1, characterized in that, The magnetic eutectic solvent is tri-n-octylphosphine oxide, aniline, and cobalt chloride; the molar ratio of tri-n-octylphosphine oxide, aniline, and cobalt chloride is 2:2:0.

5.

3. The method for preparing the magnetic eutectic solvent according to claim 1 or 2, characterized in that, Includes the following steps: The magnetic eutectic solvent is obtained by mixing hydrogen bond acceptor, hydrogen bond donor and cobalt chloride; The mixing is carried out under stirring conditions, the stirring temperature is 70~80℃, the stirring speed is 700~1000rpm, and the stirring time is 18~22min.

4. The application of the magnetic eutectic solvent of claim 1 or 2 or the magnetic eutectic solvent prepared by the preparation method of claim 3 as an extractant.

5. The application according to claim 4, characterized in that, The magnetic eutectic solvent was used as an extractant for the enrichment of antidepressants.

6. A pretreatment method for wastewater containing antidepressant drugs, characterized in that, Includes the following steps: The pH of the wastewater is adjusted to 6-10, and the salt concentration is adjusted to 0-25% to obtain conditioned wastewater; The conditioning wastewater and extractant were mixed and vortexed, then allowed to stand. The magnetic eutectic solvent phase was collected to obtain the enriched antidepressant. The extractant is the magnetic eutectic solvent of claim 1 or 2 or the magnetic eutectic solvent prepared by the preparation method of claim 3.

7. The pretreatment method according to claim 6, characterized in that, The wastewater contains one or more of the following antidepressants: paroxetine, nortriptyline, fluoxetine, and clomipramine. The volume ratio of the conditioning wastewater to the extractant is 190~210:1; The rotational speed of the vortex oscillation is 1000~1200 rpm, and the duration of the vortex oscillation is 20~70 s; The method for collecting the magnetic eutectic solvent phase is to use a microsyringe to collect droplets of the magnetic eutectic solvent phase.

8. A method for detecting the content of antidepressants in wastewater, characterized in that, Includes the following steps: Wastewater is pretreated to obtain enriched antidepressant drugs; the pretreatment method is the pretreatment method according to claim 6 or 7; The enriched antidepressant drug was mixed with a low-viscosity organic solvent to obtain the test solution; The test solution was subjected to high performance liquid chromatography (HPLC) to obtain an HPLC chromatogram. The peak areas of different analytes in the high performance liquid chromatography (HPLC) spectra were substituted into the standard curves of the corresponding analytes to obtain the content of antidepressants in the wastewater.

9. The detection method according to claim 8, characterized in that, The low-viscosity organic solvent includes methanol or acetonitrile; The volume ratio of the enriched antidepressant to the low-viscosity organic solvent is 0.8~1.2:1; The high-performance liquid chromatography (HPLC) detection column is a C18 column, and the detector is an ultraviolet detector.

10. The detection method according to claim 8 or 9, characterized in that, The high-performance liquid chromatography (HPLC) detection includes the following conditions: column temperature: 25~30℃, flow rate: 0.8~1.2 mL·min. -1 Detection wavelength: 210~220nm, injection volume: 10~20μL, mobile phase: mobile phase A is methanol, mobile phase B is 0.1% (w / w) aqueous solution of phosphoric acid, gradient elution program: 0~3min, volume fraction of mobile phase A is 45%; 3~20min, volume fraction of mobile phase A increases linearly from 45% to 52%; 20~40min, volume fraction of mobile phase A increases linearly from 52% to 65%; 40~45min, volume fraction of mobile phase A is 65%.

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