Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism
Identification and evaluations of pesticide metabolites are necessary for risk assessment and toxicological research. In this study, the metabolites of penflufen (a widely used chiral pesticide) in rat liver microsomes were identified using liquid chromatography Q-Exactive Plus mass spectrometry. In...
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| Format: | Article |
| Language: | English |
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Elsevier
2023-02-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651323000532 |
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| author | Shanshan Di Ruiquan Liu Zhenzhen Liu Hao Xu Huiyu Zhao Yuele Lu Peipei Qi Zhiwei Wang Xinquan Wang |
| author_facet | Shanshan Di Ruiquan Liu Zhenzhen Liu Hao Xu Huiyu Zhao Yuele Lu Peipei Qi Zhiwei Wang Xinquan Wang |
| author_sort | Shanshan Di |
| collection | DOAJ |
| description | Identification and evaluations of pesticide metabolites are necessary for risk assessment and toxicological research. In this study, the metabolites of penflufen (a widely used chiral pesticide) in rat liver microsomes were identified using liquid chromatography Q-Exactive Plus mass spectrometry. In total, 17 penflufen metabolites were identified, and most of them were hydroxylation products, which were generated by oxygenation at different candidate sites of penflufen. The relative abundance of metabolite M12 (penflufen-3-hydroxy-butyl, 32 %) was the largest, followed by M8 (15.6 %) and M2 (12.8 %). The major metabolite penflufen-3-hydroxy-butyl was first synthesized by 11 reactions with a 99.73 % purity. The absolute configuration of M12 enantiomers were confirmed after preparing enantiomers, and establishing the enantioseparation method. The M12 enantiomers toxicity to Danio rerio (LC50, >10 mg/L) and four kinds of phytopathogens (EC50, 148–34969 mg/L) were significantly lower than parents (LC50, 0.449–24.3 mg/L; EC50, 0.027–92.0 mg/L). In rat liver microsomes, approximately 40–47 % of the penflufen enantiomers were metabolized to M12 enantiomers, and R-penflufen was preferentially metabolized. The generation concentrations of S-M12 were higher than R-M12 after 10 min, and the metabolic half-lives of R-M12 (29.0–32.5 min) were shorter than S-M12 (35.2–38.1 min), and were approximately 4 times longer than parent penflufen enantiomers (4.5–9.5 min). Simultaneously, the generated contents (relative contents) of M8 (27.1–57 %) and M10 (2.22–8.36 %) from S-penflufen were lower than those from R-penflufen (M8, 24.7–92.4 %; M10, 27.4–69.5 %). The enantioselective evaluations of M12, M10 and M8 deserve further study. These findings were helpful in understanding the fate and risks of chiral penflufen. |
| first_indexed | 2024-04-10T18:29:41Z |
| format | Article |
| id | doaj.art-3abb15f3ccec40d986b1391b5bdc33c2 |
| institution | Directory Open Access Journal |
| issn | 0147-6513 |
| language | English |
| last_indexed | 2024-04-10T18:29:41Z |
| publishDate | 2023-02-01 |
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| series | Ecotoxicology and Environmental Safety |
| spelling | doaj.art-3abb15f3ccec40d986b1391b5bdc33c22023-02-02T04:47:04ZengElsevierEcotoxicology and Environmental Safety0147-65132023-02-01251114549Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolismShanshan Di0Ruiquan Liu1Zhenzhen Liu2Hao Xu3Huiyu Zhao4Yuele Lu5Peipei Qi6Zhiwei Wang7Xinquan Wang8State Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR ChinaInstitute of Fermentation Engineering and College of Biotechnology and Bioengineering, Zhejiang University of Technology, Hangzhou 310014, PR ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR ChinaState Key Laboratory for Managing Biotic and Chemical Threats to the Quality and Safety of Agro-products/ Key Laboratory of Detection for Pesticide Residues and Control of Zhejiang, Institute of Agro-product Safety and Nutrition, Zhejiang Academy of Agricultural Sciences, Hangzhou 310021, PR China; Agricultural Ministry Key Laboratory for Pesticide Residue Detection, Hangzhou 310021, PR China; Correspondence to: Desheng Middle Road 298, Hangzhou, Zhejiang 310021, PR China.Identification and evaluations of pesticide metabolites are necessary for risk assessment and toxicological research. In this study, the metabolites of penflufen (a widely used chiral pesticide) in rat liver microsomes were identified using liquid chromatography Q-Exactive Plus mass spectrometry. In total, 17 penflufen metabolites were identified, and most of them were hydroxylation products, which were generated by oxygenation at different candidate sites of penflufen. The relative abundance of metabolite M12 (penflufen-3-hydroxy-butyl, 32 %) was the largest, followed by M8 (15.6 %) and M2 (12.8 %). The major metabolite penflufen-3-hydroxy-butyl was first synthesized by 11 reactions with a 99.73 % purity. The absolute configuration of M12 enantiomers were confirmed after preparing enantiomers, and establishing the enantioseparation method. The M12 enantiomers toxicity to Danio rerio (LC50, >10 mg/L) and four kinds of phytopathogens (EC50, 148–34969 mg/L) were significantly lower than parents (LC50, 0.449–24.3 mg/L; EC50, 0.027–92.0 mg/L). In rat liver microsomes, approximately 40–47 % of the penflufen enantiomers were metabolized to M12 enantiomers, and R-penflufen was preferentially metabolized. The generation concentrations of S-M12 were higher than R-M12 after 10 min, and the metabolic half-lives of R-M12 (29.0–32.5 min) were shorter than S-M12 (35.2–38.1 min), and were approximately 4 times longer than parent penflufen enantiomers (4.5–9.5 min). Simultaneously, the generated contents (relative contents) of M8 (27.1–57 %) and M10 (2.22–8.36 %) from S-penflufen were lower than those from R-penflufen (M8, 24.7–92.4 %; M10, 27.4–69.5 %). The enantioselective evaluations of M12, M10 and M8 deserve further study. These findings were helpful in understanding the fate and risks of chiral penflufen.http://www.sciencedirect.com/science/article/pii/S0147651323000532Metabolites identificationPenflufen-3-hydroxy-butyl synthesisAbsolute configurationAccurate quantificationEnantioselective metabolism |
| spellingShingle | Shanshan Di Ruiquan Liu Zhenzhen Liu Hao Xu Huiyu Zhao Yuele Lu Peipei Qi Zhiwei Wang Xinquan Wang Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism Ecotoxicology and Environmental Safety Metabolites identification Penflufen-3-hydroxy-butyl synthesis Absolute configuration Accurate quantification Enantioselective metabolism |
| title | Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism |
| title_full | Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism |
| title_fullStr | Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism |
| title_full_unstemmed | Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism |
| title_short | Comprehensive evaluation of chiral penflufen metabolite (penflufen-3-hydroxy-butyl): Identification, synthesis, enantioseparation, toxicity and enantioselective metabolism |
| title_sort | comprehensive evaluation of chiral penflufen metabolite penflufen 3 hydroxy butyl identification synthesis enantioseparation toxicity and enantioselective metabolism |
| topic | Metabolites identification Penflufen-3-hydroxy-butyl synthesis Absolute configuration Accurate quantification Enantioselective metabolism |
| url | http://www.sciencedirect.com/science/article/pii/S0147651323000532 |
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