A method for treating wastewater containing fentanyl drugs

Abstract

The present application relates to advanced oxidation technology and sewage treatment technical field, particularly to a kind of fentanyl-containing drug sewage treatment method.The treatment method includes the following steps: fentanyl-containing drug sewage is pretreated, and pH is adjusted to be acidic, to obtain acidified sewage;Nano zero-valent iron (Fe 0 ) and hydrogen peroxide solution are added to the acidified sewage, and reaction is carried out at room temperature, to realize the degradation of fentanyl in fentanyl-containing drug sewage.The method has the following advantages:1.high efficiency removal: fentanyl removal rate reaches 99% within 60 minutes.2.environmental friendly: Fe 0 And H2O2 are used, and reaction by-product is non-toxic iron oxide, without secondary pollution risk.3.strong adaptability: suitable for different pH (2-4) and sewage scale, low cost, easy to industrial application.4.product is clear: first systematic identification 11 kinds of TPs, to clarify degradation path (such as hydroxyl substitution, piperidine ring fracture etc.).

Description

Technical Field

[0001] This invention relates to the fields of advanced oxidation technology and wastewater treatment technology, and in particular to a method for treating wastewater containing fentanyl-related drugs. Background Technology

[0002] Fentanyl-related drugs are widely used in the medical field due to their potent analgesic effects. However, their extremely high lipid solubility (log P = 4.05) and bioaccumulation have led to increasingly serious persistent environmental pollution problems. Studies have shown that the residual concentration of fentanyl-related drugs in wastewater treatment plant effluent is 100% detectable, with concentrations ranging from 0 to 87 ng / L (Gushgarie et al., Water Research, 2019, 161:171-180). In contrast, conventional wastewater treatment methods, including MBR, ultraviolet light, and chlorination, only achieve a removal rate of 1.59% for fentanyl and its common metabolite nofentanyl (Simpson et al., Chemosphere, 2024, 364:143307). More seriously, in traditional chlorination disinfection processes (such as hypochlorite oxidation), the benzene ring and piperidine groups of fentanyl are easily attacked and substituted in the presence of active chlorine, generating more toxic fentanyl derivatives, such as β-hydroxyfentanyl and methoxyfentanyl. The acute toxicity (LC50 = 1.55 mg / L) of β-hydroxyfentanyl and methoxyfentanyl in zebrafish embryos is significantly higher than that of the parent compound (LC50 = 5.2 mg / L) (data from the U.S. Environmental Protection Agency (EPA) model ECOSAR.V.2.2), and they can accumulate through the food chain and threaten human health.

[0003] Currently, wastewater treatment technologies for fentanyl mainly rely on traditional chemical oxidation methods such as hypochlorite oxidation and peracetic acid treatment. However, these methods have significant limitations: (1) Byproduct toxicity risk: During the oxidation process, intermediate products (TPs) with the structural characteristics of the parent fentanyl are easily generated, especially chlorinated derivatives produced by the chlorination process, whose toxicity may be higher than that of the original compound; (2) Incomplete degradation: Traditional processes (peracetic acid, hypochlorite, and liquid chlorine) have insufficient ability to identify and remove TPs, resulting in the risk of secondary pollution. Residual hydroxylated or methoxylated intermediate products (such as β-hydroxyfentanyl, methoxyfentanyl, etc.) still have strong ecotoxicity (LC50 ~ = 1.2 ~ 3.73 mg / L, data from the US Environmental Protection Agency (EPA) model ECOSAR.V.2.2); (3) Lack of ecotoxicity assessment: Existing studies mostly focus on the removal rate of the parent compound, and there is a serious lack of assessment of the degradation pathway and the ecotoxicity of wastewater, resulting in the hidden danger of "incomplete degradation and unresolved risks" in wastewater treatment processes.

[0004] In recent years, based on zero-valent iron (Fe)0 Advanced oxidation technology (Fe) 0 Due to their high reducing activity and low cost, zero-valent iron (ZPO) systems have been used to degrade antibiotics such as sulfamethoxazole (Shanableh, et al., Sci. Total Environ, 2021, 761:143307) and pesticides such as atrazine (Shen, et al., J. Hazard. Mater, 2018, 357:408-414). However, the application of ZPO systems in the field of opioid treatment still faces the following technical bottlenecks: (1) Passivation problem: The surface of ZPO is easily passivated to form an oxide layer, which leads to a reduction in active sites and a significant decrease in degradation efficiency with reaction time; (2) Unclear degradation pathway: The types of TPs generated during degradation are complex, especially the generation of highly toxic chlorinated products in traditional chlorination processes needs to be avoided, but existing technologies lack systematic identification of their structure, toxicity and degradation pathway, and cannot assess the environmental safety of the technology; (3) Lack of product identification: Traditional analytical methods (such as LC-MS / MS targeted detection) are limited by the database coverage, making it difficult to achieve non-targeted screening of unknown TPs, which restricts the in-depth analysis of degradation mechanisms.

[0005] To address the aforementioned issues, there is an urgent need to develop a highly efficient, environmentally friendly fentanyl wastewater treatment technology with product traceability capabilities. Summary of the Invention

[0006] Based on the above, the present invention provides a method for treating wastewater containing fentanyl-related drugs.

[0007] To achieve the above objectives, the present invention provides the following solution:

[0008] One of the technical solutions of this invention is a method for treating wastewater containing fentanyl-related drugs, comprising the following steps:

[0009] Wastewater containing fentanyl-related drugs is pretreated and its pH is adjusted to acidic to obtain acidified wastewater;

[0010] Nano-zero ferric iron and hydrogen peroxide solution were added to the acidified wastewater and reacted at room temperature to achieve the degradation of fentanyl-related drugs in the wastewater containing fentanyl-related drugs.

[0011] The second technical solution of this invention is a method for comprehensive evaluation of degradation products of fentanyl-related drugs in wastewater, comprising the following steps:

[0012] Wastewater was treated using the above-described method. During the reaction of the acidified wastewater with nano-zero-valent iron and hydrogen peroxide solution at room temperature, samples were taken at 0, 10, 30, and 60 minutes of the reaction and filtered through a 0.22 μm filter membrane. The degradation products in the resulting filtrate were analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) for non-targeted analysis. Subsequently, Compound Discoverer 3.1 software was used for non-targeted screening, matching the fentanyl-related compound database, and inferring the product structure based on fragment ion characteristics.

[0013] The present invention discloses the following technical effects:

[0014] The method of this invention has the following advantages: 1. High efficiency removal: Fentanyl removal rate reaches 99% within 60 minutes, avoiding problems such as residual benzene derivatives in traditional methods. 2. Environmentally friendly: Using Fe... 0 It reacts with H2O2, producing non-toxic iron oxide as a byproduct, posing no risk of secondary pollution. 3. High adaptability: Applicable to different pH levels (2-4) and wastewater scales, with low cost and easy industrial application. 4. Clear products: For the first time, 11 types of TPs were systematically identified, and their degradation pathways (such as hydroxyl substitution, piperidine ring cleavage, etc.) were elucidated.

[0015] This invention innovatively integrates zero-valent iron Fenton (Fe) 0 The H2O2 oxidation system and ultra-high pressure liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) non-targeted analysis technology not only achieved efficient removal of fentanyl (removal rate >99% within 60 minutes) and avoided the generation of highly toxic chlorinated products in the chlorination process, but also systematically identified the structure and evolution path of 11 novel degradation products for the first time, providing a scientific basis and technical guarantee for the safe treatment of fentanyl-contaminated water bodies. Attached Figure Description

[0016] To more clearly illustrate the technical solutions in the embodiments of the present invention or the prior art, the drawings used in the embodiments will be briefly introduced below. Obviously, the drawings described below are only some embodiments of the present invention. For those skilled in the art, other drawings can be obtained based on these drawings without creative effort.

[0017] Figure 1 a) Performance graphs of fentanyl degradation by zero-valent iron Fenton system under different degradation systems and materials; b) Performance graphs of fentanyl degradation by zero-valent iron Fenton system under different pH conditions; c) Reaction rate constants of fentanyl degradation by zero-valent iron Fenton system under different degradation systems and materials; d) Reaction rate constants of fentanyl degradation by zero-valent iron Fenton system under different pH conditions.

[0018] Figure 2 a) The degradation effect of fentanyl by the zero-valent iron Fenton system under different free radical quencher conditions; b) The reaction rate constant of the zero-valent iron Fenton system for fentanyl degradation under different free radical quencher conditions.

[0019] Figure 3 a), c)Fe 0 / Scanning electron microscope (SEM) image of Fe before H2O2 degradation; b), d) Fe 0 Scanning electron microscope (SEM) image of H2O2 degradation; e), f), h), i)Fe 0 Transmission electron microscopy (TEM) images of H2O2 before and after degradation; g), j)Fe 0 Scanning electron microscope-energy dispersive X-ray spectroscopy (SEM-Mapping) images.

[0020] Figure 4 a) X-ray photoelectron spectroscopy (XPS) spectra of Fe in the 2p and c) O 1s energy regions; b) Fe 0 d) Full-spectrum XPS spectra before and after the H2O2 reaction; d) Electron paramagnetic resonance (ESR) spectra of hydroxyl radicals (·OH) using DMPO as a spin trapping reagent.

[0021] Figure 5 For Fe 0 Mechanism diagram of fentanyl (FTN) degradation by the H2O2 system.

[0022] Figure 6 MS / MS mass spectra and structural formulas of 11 types of TP (P1-P11) and FTN.

[0023] Figure 7 EIC mass spectra of 11 types of TP and FTN.

[0024] Figure 8 This study analyzes the quantitative changes of TP during the degradation process in two systems; where a) represents the quantitative trend of TP in the pure water system, b) represents the quantitative trend of TP in the trichloroisocyanuric acid system, and c) and d) represent the trends of the data in both systems after data enhancement through linear interpolation.

[0025] Figure 9 For different concentrations of PO4 3- a),a1),b),b1)Cl - c),c1)CO3 2- 、d),d1)SO4 2- ,e),e1)C2O4 2-、f),f1)NO3 - The performance of the zero-valent iron-based Fenton system in degrading fentanyl is shown in the graph, along with the reaction rate constant. Detailed Implementation

[0026] Various exemplary embodiments of the present invention will now be described in detail. This detailed description should not be considered as a limitation of the present invention, but rather as a more detailed description of certain aspects, features, and embodiments of the present invention.

[0027] It should be understood that the terminology used in this invention is merely for describing particular embodiments and is not intended to limit the invention. Furthermore, with respect to numerical ranges in this invention, it should be understood that each intermediate value between the upper and lower limits of the range is also specifically disclosed. Any stated value or intermediate value within a stated range, as well as each smaller range between any other stated value or intermediate value within said range, is also included in this invention. The upper and lower limits of these smaller ranges may be independently included or excluded from the range.

[0028] Unless otherwise stated, all technical and scientific terms used herein have the same meaning as commonly understood by one of ordinary skill in the art. While only preferred methods and materials have been described herein, any methods and materials similar or equivalent to those described herein may be used in the implementation or testing of this invention. All references to this specification are incorporated by way of citation to disclose and describe methods and / or materials associated with those references. In the event of any conflict with any incorporated reference, the content of this specification shall prevail.

[0029] Various modifications and variations can be made to the specific embodiments described in this specification without departing from the scope or spirit of the invention, as will be apparent to those skilled in the art. Other embodiments derived from this specification will also be apparent to those skilled in the art. This specification and embodiments are merely exemplary.

[0030] The terms “include,” “including,” “have,” “contain,” etc., used in this article are all open-ended terms, meaning that they include but are not limited to.

[0031] Unless otherwise specified, the "%" mentioned in this invention refers to a percentage by mass.

[0032] The first aspect of this invention provides a method for treating wastewater containing fentanyl-related drugs, comprising the following steps:

[0033] Wastewater containing fentanyl-related drugs is pretreated and its pH is adjusted to acidic to obtain acidified wastewater;

[0034] Nano-zero ferric iron and hydrogen peroxide solution were added to the acidified wastewater and reacted at room temperature to achieve the degradation of fentanyl-related drugs in the wastewater containing fentanyl-related drugs.

[0035] The purpose of pretreatment is to remove large particulate matter and suspended solids from wastewater containing fentanyl-related drugs to ensure the high efficiency of subsequent reactions.

[0036] In a preferred embodiment of the present invention, the pretreatment method is precipitation or filtration; specifically, the filtration is filtration through filter paper with a pore size of 0.45 μm.

[0037] The pH adjustment to acidity is specifically achieved by adding sulfuric acid or sodium hydroxide solution to adjust the pH to 2-4.

[0038] The purpose of adjusting the pH to acidic is to optimize the Fenton reaction conditions.

[0039] In a preferred embodiment of the present invention, the mass-to-volume ratio of the nano-zero-valent iron to the fentanyl-containing wastewater is (0.05-0.2) g:1 L; the volume ratio of the hydrogen peroxide solution to the fentanyl-containing wastewater is (1.0-10.0):1000.

[0040] The hydrogen peroxide solution has a mass concentration of 30%.

[0041] In a preferred embodiment of the present invention, the mass-to-volume ratio of the nano-zero valent iron to the hydrogen peroxide solution is 0.05 g: 1 mL.

[0042] In a preferred embodiment of the present invention, the reaction is carried out under stirring conditions, with a stirring speed of 500 rpm; the reaction time is 10-60 minutes.

[0043] The processing method of this invention utilizes Fe 0 The hydroxyl radicals (·OH) generated by the / H2O2 system efficiently degrade fentanyl and its structural analogues, achieving complete removal.

[0044] A second aspect of this invention provides a method for comprehensive evaluation of degradation products of fentanyl-related drugs in wastewater, comprising the following steps:

[0045] Wastewater was treated using the above-described method. During the reaction of adding nano-zero ferric iron and hydrogen peroxide solution to the acidified wastewater at room temperature, samples were taken at 0, 10, 30, and 60 minutes of the reaction and filtered through a 0.22 μm filter membrane. The degradation products in the resulting filtrate were analyzed using ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) for non-targeted analysis. Subsequently, CompoundDiscoverer 3.1 software was used for non-targeted screening, matching the fentanyl-related compound database, and inferring the product structure based on fragment ion characteristics.

[0046] In a preferred embodiment of the present invention, the chromatographic conditions are set as follows:

[0047] Hypersil TM BDS C18 column (150 mm × 2.1 mm, 1.9 μm); column temperature 40 ℃; flow rate 0.3 mL / min; mobile phase: phase A is 0.1% formic acid aqueous solution, phase B is acetonitrile; gradient elution: 0–5 min 5% phase B, 5–15 min linearly up to 95% phase B, hold for 5 min.

[0048] In a preferred embodiment of the present invention, the mass spectrometry conditions are set as follows: Orbitrap Exploris TM 480 mass spectrometer, positive / negative ion mode combined with HCD fragmentation, acquiring full scan and target ion secondary mass spectrometry data (Full MS / dd-MS). 2 ;

[0049] By comparing the mass spectrometry data (m / z 50–500) of blank and processed samples, new chromatographic peaks were identified: signal-to-noise ratio > 3, intensity > 10. 5 With a sample / blank peak area ratio >10, and based on the fentanyl-related compound spectral library established using Compound Discover software, degradation products including hydroxylation, methoxylation, and fragmentation products were identified by matching characteristic fragment ions and retention times.

[0050] This invention uses non-targeted analysis based on HPLC-HRMS to analyze solutions of zero-valent iron (Fenton) before and after degradation. The acquired data files include ESI-positive [M+H] samples. + And ESI-negative [MH] -Retention time and peak intensity. Newly formed products were identified by comparing data from pure water fentanyl solution samples with control samples of fentanyl solution prepared from simulated disinfection wastewater, and contaminant samples treated with zero-valent iron (Fenton). Special attention was paid to chromatographic peaks that appeared only in the treated samples but were not detected in the control group. To confirm that these peaks represented newly formed compounds, a threshold was set in this invention: and then an integrated workflow for screening suspected and non-targeted compounds was implemented. To minimize background interference, the raw data were initially filtered using the following criteria: (1) signal-to-noise ratio (S / N) > 3, (2) intensity > 10. 5 (3) The ratio of sample intensity to program blank > 10. Then, screening was performed on pure water system and simulated disinfection wastewater system. The newly generated compounds were compared with the spectral library of 236 fentanyl compounds established in CompoundDiscover software. Based on the similarity of the parent and metabolite structures and the common characteristic fragments, the secondary characteristic fragment ions of the parent were imported into CompoundDiscoverer software for characteristic fragment search to determine the structure of unknown TP. In this way, the unknown compound (TP) generated by the degradation of fentanyl in the zero-valent iron Fenton system can be accurately identified.

[0051] Mass spectrometry data (m / z 50–500) of pure water fentanyl solution samples were compared with those of control samples of fentanyl solution prepared from simulated disinfection wastewater, as well as samples degraded by zero-valent iron (Fenton). Unknown peaks were identified using high-performance liquid chromatography-mass spectrometry (HPLC-MS / MS) in electrospray ionization positive ion mode.

[0052] Linear interpolation is a method of estimation between known data points, based on the assumption that the data varies linearly between adjacent points. Given two known data points (x0, y0) and (x1, y1), for any x ∈ [x...]... 0， [x1], the y-value of the interpolation point can be calculated using the linear interpolation formula:

[0053]

[0054] Time-series data on the amount of degraded substances varying over time (per minute) was constructed using linear interpolation. However, since the data obtained by linear interpolation may be somewhat coarse, a smoothing method was further employed to optimize the time-series data. Specifically, a smoothing method based on moving average was used for each data point S. i Calculate the mean of p (smoothing values) points before and after the smoothing value to reduce data noise and make the time series trend more stable. The smoothing calculation formula is as follows:

[0055]

[0056] Where si represents the smoothed data, p represents the smoothing window size, and si+j represents the unsmoothed data at time i+j.

[0057] This invention achieves complete removal of fentanyl through a zero-valent iron Fenton system, avoiding problems such as residual benzene derivatives found in traditional methods. It is the first to employ dynamic monitoring using a combination of a zero-valent iron Fenton system and UHPLC-HRMS non-targeted analysis to systematically identify 11 TPs (P1-P11) generated during the degradation process, including hydroxylation, methoxylation, and cleavage products. The Chinese names, structural formulas, and molecular formulas of P1-P11 are as follows:

[0058] P1

[0059] Chinese name: Methoxyfentanyl

[0060] Structural formula: The oxygen atom of the amide group (-CON-) in the fentanyl molecule is replaced by a methoxy group (-OCH3).

[0061]

[0062] Molecular formula: C 22 H 28 N2O2

[0063] P2-P4

[0064] Chinese name: Hydroxyfentanyl (isomer)

[0065] Structural formula: Hydroxyl groups (-OH) are introduced at different positions of the benzene ring or piperidine ring in the fentanyl molecule.

[0066] P2: Ortho-hydroxyl substitution on the benzene ring P3: Para-hydroxyl substitution of benzene ring P4: β-hydroxy substitution at the piperidine ring (β-hydroxyfentanyl) Molecular formula: C 22 H 28 N2O2

[0067] P5-P6

[0068] Chinese name: Dihydroxyfentanyl (isomer)

[0069] Structural formula: A hydroxyl group (-OH) is introduced at each of two different positions in the fentanyl molecule (such as the benzene ring and the piperidine ring).

[0070]

[0071] Molecular formula: C 22 H 28 N2O3

[0072] P7

[0073] Chinese name: Norfentanyl (or fentanyl)

[0074] Structural formula: The methyl group (-CH3) on the piperidine ring in the fentanyl molecule is removed.

[0075]

[0076] Molecular formula: C 14 H 20 N2OP8

[0077] Chinese name: Hydroxydesmethylfentanyl

[0078] Structural formula: A hydroxyl group (-OH) is introduced onto the piperidine ring of demethylfentanyl (P7).

[0079]

[0080] Molecular formula: C 14 H 20 N2O2

[0081] P9

[0082] Chinese name: 4-[phenyl(propionyl)amino]piperidine-1-carboxylic acid ethyl ester.

[0083] Structural formula: The 1-position of the piperidine ring is an ethyl carboxylate group, and the 4-position is a phenylpropionamide group.

[0084]

[0085] Molecular formula: C 17 H 24 N2O3

[0086] P10

[0087] Chinese name: 2-[ethyl(butyl)amino]-1-phenylethanol. Structural formula: A benzene ring is attached to an ethanol group (-CH2CH2OH), and the amino group is substituted with ethyl and butyl groups.

[0088]

[0089] Molecular formula: C 14 H 23 NOP11

[0090] Chinese name: N-ethyl-N-(4-hydroxyphenyl)acetamide. Structural formula: The nitrogen atom of the acetamide group (-CONH-) is linked to the ethyl group and the 4-hydroxyphenyl group.

[0091]

[0092] Molecular formula: C 11 H 15 NO2

[0093] This invention provides a method for treating wastewater containing fentanyl-related drugs, while simultaneously identifying intermediate conversion products to assess the complete degradation potential of fentanyl. This invention employs a dynamic monitoring technique combining a zero-valent iron Fenton system and UHPLC-HRMS non-targeted analysis. Ultra-high performance liquid chromatography-high resolution mass spectrometry (UHPLC-HRMS) non-targeted analysis identifies 11 novel conversion products (TPs), determining their removal mechanisms and degradation pathways. The method achieves a 99% removal rate of fentanyl-related drugs within 60 minutes. This invention combines high efficiency, environmental friendliness, and scientific rigor, providing a solution for the treatment of fentanyl-contaminated water bodies.

[0094] Unless otherwise specified, the technical solutions described in this invention are all conventional solutions in the field, and the reagents or raw materials used are all purchased from commercial channels or are publicly available unless otherwise specified.

[0095] 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.

[0096] Example 1

[0097] 1. Experimental Materials and Equipment

[0098] 1.1 Reagents:

[0099] Fentanyl standard (purity ≥98%, Sigma-Aldrich); Nano-zero valent iron (Fe) 0 Purity ≥99%, particle size 50-100nm (Aladdin); 30% hydrogen peroxide solution (H2O2, Sinopharm Group); sulfuric acid (H2SO4, analytical grade), sodium hydroxide (NaOH, analytical grade); ultrapure water (resistivity ≥18.2MΩ·cm, prepared by Milli-Q system).

[0100] 1.2 Instruments:

[0101] pH meter (Mettler Toledo FE28); magnetic stirrer (IKARCT Basic); ultra-high performance liquid chromatography-high resolution mass spectrometry system (UHPLC-HRMS, Thermo Scientific Vanquish Flex UHPLC+OrbitrapExploris 480); scanning electron microscope (SEM, Hitachi SU8010); X-ray photoelectron spectroscopy (XPS, Thermo Scientific K-Alpha).

[0102] 2. Experimental Procedure

[0103] (1) Wastewater pretreatment: Take 1L of fentanyl solution (with an effective chlorine concentration of 10mg / L and an initial fentanyl concentration of 1mg / L) prepared from simulated disinfection wastewater, filter it through filter paper (pore size 0.45μm) to remove suspended solids and large particulate impurities, and obtain pretreated wastewater.

[0104] (2) Acidification to adjust pH: Add 0.1M H2SO4 solution to the pretreated wastewater to adjust the pH to 3.0±0.1, and stir continuously for 5 minutes to make the solution uniform.

[0105] (3) Fenton oxidation reaction: Add 0.05g of nano-zero valent iron (Fe) to 1L of acidified wastewater. 0 ) and 1 mL of 30% H2O2 solution, with a dosage ratio of Fe 0 H2O2 = 0.05g: 1mL.

[0106] The reaction was stirred at 500 rpm at room temperature (25±1℃). Samples were taken at 0, 10, 30 and 60 minutes of the reaction. After sampling, a quencher was added to immediately terminate the reaction and the sample was filtered through a 0.22 μm filter membrane.

[0107] (4) Degradation product analysis

[0108] UHPLC conditions:

[0109] Column: Hypersil BDS C18 (150mm × 2.1mm, 1.9μm);

[0110] Mobile phase: Phase A (0.1% formic acid aqueous solution), Phase B (acetonitrile);

[0111] Gradient elution: 0–5 min 5% B, 5–15 min linearly increase to 95% B, hold for 5 min;

[0112] Flow rate: 0.3 mL / min; Column temperature: 40℃.

[0113] HRMS requirements:

[0114] Ion source: Electrospray ionization (ESI), positive ion mode;

[0115] Scan range: m / z 50~1000;

[0116] Resolution: 120,000 (Full MS), 30,000 (MS / MS);

[0117] Fragmentation mode: HCD (High-energy collision-induced dissociation), energy 30 eV.

[0118] Data analysis: Non-targeted screening was performed using CompoundDiscoverer 3.1 software, matching the fentanyl-related compound database (containing 236 structures), and the product structure was inferred by combining fragment ion characteristics.

[0119] 3. Experimental Results

[0120] (1) Fentanyl degradation efficiency

[0121] Removal rate: Fentanyl removal rate reaches 99.2% within 60 minutes. Figure 1 As shown in Figure a), ZVI(98%) + 0.0025g indicates that the reaction conditions are the addition of 98% pure Fe to 1L of acidified wastewater. 0 The dosage is 0.0025g, and ZVI (98%) + 0.01g indicates that the reaction conditions are the addition of 98% pure Fe to 1L of acidified wastewater. 0 The dosage is 0.01g, and ZVI (99%) + 0.0025g indicates that the reaction conditions are the addition of 99% pure Fe to 1L of acidified wastewater. 0 The dosage is 0.0025g, and ZVI (99%) + 0.01g indicates that the reaction conditions are the addition of 99% pure Fe to 1L of acidified wastewater. 0 The dosage is 0.01g, and ZVI / H2O2 indicates the reaction conditions are: adding 0.0025g of 99% pure Fe to 1L of acidified wastewater. 0 And 50 μL of 30% H2O2, where H2O2 indicates that the reaction condition is to add only 50 μL of 30% H2O2 to 1L of acidified wastewater, and ZVI indicates that the reaction condition is to add only 0.0025g of 99% pure Fe to 1L of acidified wastewater. 0 ;

[0122] Removal rate: The total organic carbon (TOC) removal rate was 98.7%, indicating that fentanyl was almost completely converted into CO2 and H2O.

[0123] (2) Identification of degradation products

[0124] Eleven novel transformation products (TPs) were identified using HRMS non-targeted analysis, including hydroxylation products (P1–P6), methoxylation products (P7–P8), and fragmentation products (P9–P11). Their specific characteristics are as follows:

[0125] P1~P4: m / z 353.22247(C 22 H 28 N2O2), is the hydroxylated fentanyl isomer ( Figure 6 );

[0126] P7: m / z 234.10760(C 14 H 20 N2O), corresponding to nofentanyl ( Figure 6 );

[0127] P10: m / z 222.18526 (C 14 H 23 NO), which is a product of piperidine ring cleavage (Table 1).

[0128] Table 1

[0129]

[0130] As shown in Table 1, to further elucidate the structures of the 11 unknown TPs detected, this invention utilized CompoundDiscover software for analysis. Based on the molecular formula calculations, the retention time tolerance was 0.1 min, and the m / z tolerance was 0.015 Da. The ratio of the sample peak area to the reference peak area (t0) must be greater than 10 times to be considered a TP of Fentanyl. Table 1 includes all possible candidate m / z values. Among them, P1-P8 are TPs generated from the degradation of fentanyl contaminant solutions prepared with ultrapure water. P9 is a newly discovered product in the simulated disinfection system, and P10 and P11 are fragmentation products resulting from further degradation of the degradation products in a zero-valent iron system. Therefore, the interpretation of the precursor molecular structure is mainly based on fragmentation by secondary mass spectrometry.

[0131] Non-targeted analysis results of mass spectrometry, such as Figure 6 , Figure 7 As shown, the MASS Frontier assay was used to analyze the fragmentation mode of fentanyl, providing a basis for structural identification. FTN shows [M+H] at m / z 337.22740. + The ion produces a characteristic fragment of phenethyl with m / z 105.06982 and a characteristic fragment of phenethylpiperidine with m / z 188.14334, representing the protonated phenethyl ion [C8H9]. + and phenylethylpiperidine ion [C 13 H 18 N] + .

[0132] P1-P4 are isomers with m / z 353.22247. The MS / MS spectrum of P1 shows the presence of the same characteristic fragment as the FTN parent compound. Therefore, it can be determined that its fragmentation mode also produces two characteristic fragments with similar m / z values ​​of 105.06982 and 188.14334. This indicates that the oxygen substitution in P1 occurs on the amide group. Structural comparison suggests that P1 is methoxyfentanyl. For P2-P4, by matching retention times and comparing MS and MS / MS spectra with the FTN, the two characteristic fragments corresponding to m / z 121.06475 and m / z 204.13823 each have an added oxygen atom, consistent with the result of hydroxyl substitution. Therefore, the characteristic fragments containing m / z 121.06475 and m / z 204.13823 represent hydroxyfentanyl with different hydroxyl substitution positions. The m / z 121.06475 corresponds to the characteristic fragment where the benzyl group is substituted with a hydroxyl group, and the m / z 204.13823 corresponds to the characteristic fragment where the benzene ring on phenethylpiperidine is substituted with a hydroxyl group. Similarly, P5 and P6 contain two characteristic fragments, m / z 121.06475 and m / z 204.13823, but based on the m / z of the parent ion, it can be deduced that P5 and P6 are two dihydroxyfentanyl structures with different hydroxyl substitution positions.

[0133] Both P7 and P8 exhibit a characteristic fragment ion at m / z 84.08057, a feature consistent with the piperidine ring, indicating that both compounds contain a piperidine ring structure. Furthermore, considering the mass-to-charge ratio of the parent ions, the mass spectrometric data of P7 matches that of nofentanil, thus confirming P7 as nofentanil. The parent ion of P8 has an additional oxygen atom compared to P7, and P7 and P8 show highly similar mass spectrometric patterns, indicating they have similar molecular structures. Based on this observation, it can be inferred that P8 is likely a hydroxylated derivative of P7, namely hydroxynofentanil.

[0134] P9 was found in a simulated disinfection system, distinct from TP in a pure water system. Mass spectrometry data showed that P9 contained a piperidine ring characteristic fragment at m / z 84.08084 and a piperidine carboxylate characteristic fragment at m / z 156.10190. Therefore, the structure of P9 can be deduced as 4-[phenyl(propionyl)amino]piperidine-1-carboxylate.

[0135] P10 and P11 are likely further fragmentation and degradation products under the zero-valent iron system. Characteristic fragment analysis revealed that the MS / MS value of P10 (m / z 177.12738) corresponds to the 2-[ethyl(methyl)amino]-1-phenylethanol ion. The structure of P10 can be deduced through characteristic fragment comparison.

[0136] P11 is a product of further degradation. Analysis of characteristic fragment ions revealed characteristic fragment ions at m / z 107.04916 and m / z 135.04402, which are protonated hydroxybenzene ions and hydroxybenzamide ions, respectively. Therefore, the structure of P11 is deduced to be N-ethyl-N-(4-hydroxyphenyl)acetamide.

[0137] Meanwhile, based on the monitoring results of the above degradation products in high-resolution mass spectrometry at different times, such as Figure 8 As shown in a) and b), the aforementioned unknown TPs all follow a logical increase-decrease pattern over time, increasing sharply in the first 5-10 minutes and then decreasing sharply thereafter. This behavior can be attributed to the fact that they are all degradation products of fentanyl, and that the zero-valent iron system successfully degrades fentanyl and its byproducts, avoiding the residue of highly toxic derivatives.

[0138] To further quantify the stability of substances during the degradation process, this invention introduces the concept of half-life. 4 The half-life metric describes the time required for a substance to decline from its peak value to half its original value. Based on half-life analysis, significant differences in degradation rates were observed among different substances. Figure 8 As shown in c), compared to P11 and P7, P8 and P2 exhibit slower degradation rates, with half-lives of 15 minutes and 12 minutes, respectively. The latter's degradation rate is approximately half that of the former. Furthermore, Figure 8 (d) shows that P4 has the highest degradation difficulty, requiring more than three times the time of P10 to degrade, with a half-life of 31 minutes.

[0139] Example 2

[0140] Comparison between different degradation systems

[0141] Three different systems (Fe) were tested. 0 H2O2, Fe 0 / H2O2), comparing the use of Fe alone. 0 (ZVI), using H2O2 alone, Fe 0 The degradation performance of fentanyl under different system methods such as H2O2 system treatment (i.e., based on the experimental steps in section 2, only 0.0025g of nano-zero valent iron (Fe) was added). 0 ) and 50 μL of 30% H2O2 solution were replaced with only 0.0025 Fe 0 Only 50 μL of 30% H2O2 solution was added, along with 0.0025 g of nano-zero valent iron (Fe). 0(Using 50 μL of 30% H2O2, with all other steps and parameters unchanged), the results showed that the removal rates of fentanyl within 60 minutes were 11.40%, 6.20%, and 94.65%, respectively. Fentanyl exhibits a high removal rate in the zero-valent iron Fenton system within 60 minutes. Figure 1 As shown in a) of the diagram. From Figure 1 From c), it can be seen that Fe 0 The degradation rate constant of fentanyl by the H2O2 system can reach 0.1192 min. -1 .

[0142] Effects of different pH values

[0143] The effect of different pH values ​​(pH = 1, 3, 5, 7, 9) on degradation was investigated (i.e., based on the experimental steps in section 2, only the pH was adjusted to 1, 5, 7, and 9, while all other steps and parameters remained unchanged). The experimental results at different pH values ​​are as follows: Figure 1 As shown in b), the degradation performance of fentanyl reaches its optimal level at a solution pH of 3. As the pH increases, the degradation performance decreases, reaching only 70% at pH 9. This is because at pH 3, ferrous species primarily exist as free Fe. 2+ This form exists, which is the basis for the generation of hydroxyl radicals. The optimal conditions are as follows. Hydroxyl radicals are key reactive species in Fenton-like reactions, responsible for the degradation of organic matter. When the pH is too high, ferric species in the solution begin to form large amounts of iron sludge precipitate, leading to a sharp decrease in reactivity. When the pH is <3, which is too low, hydrogen peroxide (H2O2) readily protonates to form H3O2. + This form of hydrogen peroxide cannot be catalyzed by iron species to produce hydroxyl radicals (·OH), thus severely affecting the oxidative degradation of organic matter. Figure 1 As can be seen in d), the degradation rate constant of fentanyl can reach 0.14577 min at pH 3. -1 .

[0144] Reaction mechanism verification

[0145] Free radical contribution analysis: through quenching experiments ( Figure 2 In the diagram, L-Histidine represents L-histidine, BQ represents benzoquinone, TBA represents tert-butanol, MeOH represents methanol, and AgNO3 represents silver nitrate. Figure 2 b) confirms that hydroxyl radicals (·OH) are the main active substances in degradation (contribution rate >90%);

[0146] Fe 0 Surface characterization: SEM images show Fe after the reaction 0 A porous oxide layer is formed on the surface. Figure 3In the middle (a)-b), (c)-d), XPS confirmed Fe 0 Oxidized to Fe 2+ / Fe 3+ ( Figure 4 a)-c)) promotes the continuous generation of ·OH.

[0147] Figure 2 Free radical quenching experiments demonstrated that in Fe... 0 The role of reactive oxygen species (ROS) in the Fenton-like degradation of fentanyl. By introducing different free radical quenchers, the types of free radicals involved in the degradation reaction were identified, including hydroxyl radicals (·OH), singlet oxygen (·OH), and reactive oxygen species (·OH). 1 O2), superoxide radicals (O2) ·- Experimental results showed that the addition of benzoquinone had almost no effect on the degradation of fentanyl, indicating that superoxide radicals did not play a role in this degradation system. The degradation rate decreased slightly after the introduction of L-histidine, but it was still eventually completely degraded, indicating that singlet oxygen had a low influence on the degradation system. Further addition of tert-butanol (TBA) and methanol as hydroxyl radical quenchers significantly reduced the degradation rate, confirming the important role of hydroxyl radicals in fentanyl degradation. ESR tests were also conducted using DMPO as a spin trapping agent. Figure 4 In d), it can be observed that Fe 0 A distinct 1:2:2:1 peak DMPO-·OH signal was detected in the / H2O2 system, and the signal intensity gradually increased with the extension of reaction time, indicating continuous generation of ·OH. Combined with the results of the free radical quenching experiment, this suggests that the ·OH is Fe... 0 The main active species that play a role in degradation in the / H2O2 system.

[0148] Fe 0 The effect of purity

[0149] Fe of different purities available on the market 0 Conduct performance comparison tests, such as Figure 1 As shown in a), high-purity Fe 0 The degradation effect is better than that of low-purity zero-valent iron, with 99% Fe. 0 It can degrade, and the degradation effect increases with increasing dosage. High-purity Fe 0 High-purity Fe exhibits higher efficiency in degrading organic pollutants. 0 It has more active sites, thus providing more opportunities for reduction reactions. Meanwhile, low-purity Fe... 0 The presence of certain impurities in the Fe alloy can affect the electron transfer rate. Low-purity Fe... 0It is easier for an oxide layer to form on the surface, which hinders its contact with contaminants and reduces effective reduction reactions.

[0150] according to Figure 3 The scanning electron microscope (SEM) results for (a)-b), (c)-d) show that Fe 0 Fe before and after H2O2 treatment 0 The surface morphology is relatively smooth, and after Fe... 0 After H2O2 treatment, Fe 0 The surface is corroded, forming a rough deposit layer and numerous porous structures. This indicates that in Fe... 0 Simultaneous oxidation and deposition occur on the surface. The reason for this phenomenon may be related to Fe. 0 An iron oxide layer formed on the surface. For example... Figure 3 The EDS plots of i) and j) show the Fe before and after the reaction. 0 The surface oxygen atom distribution was significantly increased. These results indicate a significant increase in the Fe0 surface oxide layer before and after the reaction. Figure 3 The HRTEM (high-resolution transmission electron microscopy) results of f), g), h), i) show that Fe 0 The particles aggregate into clusters, and their surfaces are surrounded by a pre-existing iron oxide film, corresponding to the (111) plane of Fe₂O₃ with a lattice spacing of 0.30 nm. After the reaction, Fe… 0 The particle size was significantly reduced, and combined with the previous SEM results, Fe 0 The surface becomes rougher, likely due to the formation of Fe oxide / hydroxide layers. This is confirmed by two different planes corresponding to 0.28 nm and 0.33 nm, respectively, on the (220) and (110) planes of Fe3O4 and FeOOH. 0 Molar ratio test with H2O2.

[0151] Fe with different molar ratios 0 The effect of / H2O2 on the generation of hydroxyl radicals (·OH) can be investigated, for example, by using free radical capture experiments (such as ESR) to demonstrate that the ·OH yield is highest at a specific ratio (1g:1mL). Based on XPS analysis of Fe before and after the reaction... 0 Further analysis of surface elements, such as Figure 4 As shown in a) and c), the peak positions of Fe 2p and O 1s can be observed. Fe(III), Fe(II), and Fe(O) are located at Fe 2p... 3 / 2 The binding energies are 711.5 eV, 709.8 eV, and 706.7 eV, respectively, while the Fe2p binding energies of Fe(Ⅲ) and Fe(II) are... 1 / 2 The peaks are located at 725.1 eV and 723.4 eV. Fe 2p 3 / 2A satellite peak exists at 718.2 eV. Furthermore, Fe 2p... 1 / 2 The satellite peak is located at approximately 731.4 eV. After PS treatment, it is compared with pure Fe. 0 In comparison, the intensity of the Fe(0) peak decreased, the proportion of Fe(II) decreased from 28.1% to 21.6%, while the proportion of Fe(III) increased from 23.4% to 26.1%, indicating that Fe(0) was gradually oxidized to Fe(II) and Fe(III) during the reaction. However, in Fe... 0 After the H2O2 reaction, the ratio of Fe(0) to Fe(II) increased again, which is consistent with the results of high-resolution transmission electron microscopy (HRTEM).

[0152] To further demonstrate the existence of ROS in the zero-valent iron Fenton system, ESR tests were performed using DMPO as a spin trapping agent. Figure 4 As shown in d), it can be observed that Fe 0 A distinct 1:2:2:1 peak DMPO-·OH signal was detected in the / H2O2 system, and the signal intensity gradually increased with the extension of reaction time, indicating continuous generation of ·OH. Combined with the results of the free radical quenching experiment, this suggests that the ·OH is Fe... 0 The main ROS in the / H2O2 system.

[0153] Interference test of different ions

[0154] In complex water matrices, PO4 3- Cl - CO3 2- SO4 2- C2O4 2- NO3 - The coexistence of anions and organic pollutants may affect the degradation efficiency of zero-valent iron-based Fenton systems through two pathways: (1) competing with the target compound for ·OH radicals; and (2) occupying active sites on the catalyst surface. Experiments show that ( Figure 9 As shown in the figure, different anions exhibit significantly different inhibitory effects on fentanyl (FTN) degradation: C2O4 2- Basically no impact, while PO4 3- Cl - SO4 2- and NO3 - The degradation efficiency of FTN decreased to 70%, 85%, 80%, and 82% (1 mM concentration), respectively, with PO4... 3- The inhibitory effect is most prominent.

[0155] PO4 3-The significant inhibitory effect can be attributed to its unique mechanism of action: on the one hand, the hydrolysis of this anion causes an increase in the pH of the system, affecting the Fenton reaction process; on the other hand, PO4... 3- It forms an inner-sphere complex with the catalyst surface through strong affinity, directly blocking the exposure of active sites. Notably, even under high salt concentration conditions of 20 mM, the system still maintains 50% (PO4) content. 3- ), 60% (Cl - SO4 2- ) and 65% (NO3) - The FTN degradation efficiency of 0.05% and its resistance to salt interference demonstrate the application potential of zero-valent iron Fenton systems in the remediation of complex water bodies.

[0156] Example 3

[0157] Traditional hypochlorite oxidation method (Xu Lin. Research on degradation methods of fentanyl compounds [D]. Beijing University of Chemical Technology, 2015): fentanyl removal rate is 85% after 60 minutes, but chlorofentanyl (m / z 371.18321, LD50) is generated. 50 (Reduced by 30%)

[0158] The method of this invention: no chlorinated products are detected, and the toxicity of TPs is significantly reduced.

[0159] Example 4

[0160] The degradation of fentanyl in wastewater (fentanyl concentration: 0.8 mg / L; COD value: 23.5 mg / L) from a pharmaceutical factory was verified according to the method in "2. Experimental Steps" of this invention (i.e., the only difference from "2. Experimental Steps" is that the simulated wastewater containing fentanyl was replaced with pharmaceutical factory wastewater). The results showed that the fentanyl removal rate was >99% after 60 minutes, and the types of total phosphorus (TPs) were consistent with the simulation experiment. Simultaneously, the potassium permanganate index of the wastewater treated using this invention decreased from 23.5 mg / L before degradation to 1.52 mg / L, indicating significant removal effects for both fentanyl and organic matter.

[0161] Example 5

[0162] According to the method in "2. Experimental Steps" of this invention, the degradation of a pharmaceutical factory wastewater (fentanyl concentration: 0.2 mg / L; COD value: 16.3 mg / L) was verified (i.e., the only difference from "2. Experimental Steps" is that the simulated wastewater containing fentanyl was replaced with pharmaceutical factory wastewater). The results showed that the removal rate of fentanyl was >99.2% after 60 minutes, and the COD value decreased from 16.3 mg / L before degradation to 1.22 mg / L. The removal effects of fentanyl and organic matter were both quite significant.

[0163] Example 6

[0164] According to the method in "2. Experimental Steps" of this invention, the degradation of a hospital wastewater (fentanyl concentration: 0.5 mg / L; COD value: 16.3 mg / L) was verified (i.e., the only difference from "2. Experimental Steps" is that the simulated wastewater containing fentanyl was replaced with hospital wastewater). The results showed that the removal rate of fentanyl was >99.4% after 60 minutes, and the COD value decreased from 16.3 mg / L before degradation to 0.26 mg / L. The removal effects of fentanyl and organic matter were both quite significant.

[0165] The embodiments described above are merely preferred embodiments of the present invention and are not intended to limit the scope of the present invention. Various modifications and improvements made by those skilled in the art to the technical solutions of the present invention without departing from the spirit of the present invention should fall within the protection scope defined by the claims of the present invention.

Claims

1. A comprehensive evaluation method for degradation products of fentanyl-related drugs in wastewater, characterized in that, Includes the following steps: The wastewater treatment process involves the following steps: First, the wastewater containing fentanyl-related drugs is pretreated and its pH is adjusted to acidic to obtain acidified wastewater. Then, nano-zero-valent iron and hydrogen peroxide solution are added to the acidified wastewater and reacted at room temperature to degrade the fentanyl-related drugs in the wastewater. During the reaction of adding nano-zero valent iron and hydrogen peroxide solution to the acidified wastewater at room temperature, samples were taken at 0, 10, 30, and 60 minutes of the reaction and filtered through a 0.22µm filter membrane. The degradation products in the resulting filtrate were analyzed non-targeted using ultra-high performance liquid chromatography-high resolution mass spectrometry. Then, non-targeted screening was performed using Compound Discoverer 3.1 software, matching the fentanyl compound database, and the product structure was inferred by combining fragment ion characteristics. The chromatographic conditions are set as follows: Hypersil TM BDS C18 column, column length 150 mm × column inner diameter 2.1 mm, packing particle size 1.9 µm; column temperature 40℃; flow rate 0.3 mL / min; Mobile phase: Phase A is 0.1% formic acid aqueous solution, and Phase B is acetonitrile; Gradient elution: 0~5 min 5% Phase B, 5~15 min linearly increase to 95% Phase B, hold for 5 min; The mass spectrometry settings are as follows: Orbitrap Exploris™ 480 mass spectrometer, positive / negative ion mode combined with HCD fragmentation, acquiring full scan and target ion secondary mass spectrometry data (Full MS / dd-MS). 2 ; By comparing the mass spectrometry data (m / z 50–500) of blank and processed samples, new chromatographic peaks were identified: signal-to-noise ratio > 3, intensity > 10. 5 With a sample / blank peak area ratio >10, and based on the fentanyl-related compound spectral library established using Compound Discover software, degradation products including hydroxylation, methoxylation, and fragmentation products were identified by matching characteristic fragment ions and retention times.

2. The method for comprehensive evaluation of fentanyl degradation products in wastewater according to claim 1, characterized in that, The pretreatment method is precipitation or filtration; the filtration is specifically filtration through filter paper with a pore size of 0.45µm. The pH adjustment to acidity is specifically achieved by adding sulfuric acid or sodium hydroxide solution to adjust the pH to 2-4.

3. The method for comprehensive evaluation of fentanyl degradation products in wastewater according to claim 1, characterized in that, The mass-to-volume ratio of the nano-zero-valent iron to the fentanyl-containing wastewater is (0.03-0.2) g:1 L; the volume ratio of the hydrogen peroxide solution to the fentanyl-containing wastewater is (0.5-10.0):1000. The hydrogen peroxide solution has a mass concentration of 30%.

4. The method for comprehensive evaluation of fentanyl degradation products in wastewater according to claim 1, characterized in that, The mass-to-volume ratio of the nano-zero-valent iron to the hydrogen peroxide solution is 0.05 g: 1 mL.

5. The method for comprehensive evaluation of fentanyl degradation products in wastewater according to claim 1, characterized in that, The reaction is carried out under stirring at a speed of 500 rpm; the reaction time is 10-60 minutes.

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