Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish
The rise of fentanyl has introduced significant new challenges to public health. To improve the examination and identification of biological samples in cases of fentanyl misuse and fatalities, this study utilized a zebrafish animal model to conduct a comparative investigation of the metabolites and...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2023-12-01
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| Series: | Frontiers in Pharmacology |
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| Online Access: | https://www.frontiersin.org/articles/10.3389/fphar.2023.1325932/full |
| _version_ | 1797387718557171712 |
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| author | Meng Liu Meng Liu Meng Liu Jian Huang Sen Zhao Bin-jie Wang Hong Zhou Yao Liu Yao Liu |
| author_facet | Meng Liu Meng Liu Meng Liu Jian Huang Sen Zhao Bin-jie Wang Hong Zhou Yao Liu Yao Liu |
| author_sort | Meng Liu |
| collection | DOAJ |
| description | The rise of fentanyl has introduced significant new challenges to public health. To improve the examination and identification of biological samples in cases of fentanyl misuse and fatalities, this study utilized a zebrafish animal model to conduct a comparative investigation of the metabolites and biotransformation pathways of fentanyl in the zebrafish’s liver and brain. A total of 17 fentanyl metabolites were identified in the positive ion mode using ultra-high-pressure liquid chromatography Q Exactive HF Hybrid Quadrupole-Orbitrap mass spectrometry (UHPLC-QE HF MS). Specifically, the zebrafish’s liver revealed 16 fentanyl metabolites, including 6 phase I metabolites and 10 phase II metabolites. Conversely, the zebrafish’s brain presented fewer metabolites, with only 8 detected, comprising 6 phase I metabolites and 2 phase II metabolites. Notably, M′4, a metabolite of dihydroxylation, was found exclusively in the brain, not in the liver. Through our research, we have identified two specific metabolites, M9-a (monohydroxylation followed by glucuronidation) and M3-c (monohydroxylation, precursor of M9-a), as potential markers of fentanyl toxicity within the liver. Furthermore, we propose that the metabolites M1 (normetabolite) and M3-b (monohydroxylation) may serve as indicators of fentanyl metabolism within the brain. These findings suggest potential strategies for extending the detection window and enhancing the efficiency of fentanyl detection, and provide valuable insights that can be referenced in metabolic studies of other new psychoactive substances. |
| first_indexed | 2024-03-08T22:29:08Z |
| format | Article |
| id | doaj.art-2ab69fc208b04ac485f9a3d0edd6c701 |
| institution | Directory Open Access Journal |
| issn | 1663-9812 |
| language | English |
| last_indexed | 2024-03-08T22:29:08Z |
| publishDate | 2023-12-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Pharmacology |
| spelling | doaj.art-2ab69fc208b04ac485f9a3d0edd6c7012023-12-18T06:54:39ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122023-12-011410.3389/fphar.2023.13259321325932Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafishMeng Liu0Meng Liu1Meng Liu2Jian Huang3Sen Zhao4Bin-jie Wang5Hong Zhou6Yao Liu7Yao Liu8School of Investigation, People’s Public Security University of China, Beijing, ChinaSchool of Investigation, Zhejiang Police College, Hangzhou, ChinaKey Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, Hangzhou, ChinaInstitute of Forensic Science, Ministry of Public Security, Beijing, ChinaKey Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, Hangzhou, ChinaKey Laboratory of Drug Prevention and Control Technology of Zhejiang Province, Zhejiang Police College, Hangzhou, ChinaInstitute of Forensic Science, Ministry of Public Security, Beijing, ChinaSchool of Investigation, People’s Public Security University of China, Beijing, ChinaInstitute of Forensic Science, Ministry of Public Security, Beijing, ChinaThe rise of fentanyl has introduced significant new challenges to public health. To improve the examination and identification of biological samples in cases of fentanyl misuse and fatalities, this study utilized a zebrafish animal model to conduct a comparative investigation of the metabolites and biotransformation pathways of fentanyl in the zebrafish’s liver and brain. A total of 17 fentanyl metabolites were identified in the positive ion mode using ultra-high-pressure liquid chromatography Q Exactive HF Hybrid Quadrupole-Orbitrap mass spectrometry (UHPLC-QE HF MS). Specifically, the zebrafish’s liver revealed 16 fentanyl metabolites, including 6 phase I metabolites and 10 phase II metabolites. Conversely, the zebrafish’s brain presented fewer metabolites, with only 8 detected, comprising 6 phase I metabolites and 2 phase II metabolites. Notably, M′4, a metabolite of dihydroxylation, was found exclusively in the brain, not in the liver. Through our research, we have identified two specific metabolites, M9-a (monohydroxylation followed by glucuronidation) and M3-c (monohydroxylation, precursor of M9-a), as potential markers of fentanyl toxicity within the liver. Furthermore, we propose that the metabolites M1 (normetabolite) and M3-b (monohydroxylation) may serve as indicators of fentanyl metabolism within the brain. These findings suggest potential strategies for extending the detection window and enhancing the efficiency of fentanyl detection, and provide valuable insights that can be referenced in metabolic studies of other new psychoactive substances.https://www.frontiersin.org/articles/10.3389/fphar.2023.1325932/fullfentanylmetabolitesbiotransformation pathwaysthe liver and brain of zebrafishHR-MS |
| spellingShingle | Meng Liu Meng Liu Meng Liu Jian Huang Sen Zhao Bin-jie Wang Hong Zhou Yao Liu Yao Liu Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish Frontiers in Pharmacology fentanyl metabolites biotransformation pathways the liver and brain of zebrafish HR-MS |
| title | Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish |
| title_full | Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish |
| title_fullStr | Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish |
| title_full_unstemmed | Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish |
| title_short | Comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish |
| title_sort | comparative analysis of the metabolites and biotransformation pathways of fentanyl in the liver and brain of zebrafish |
| topic | fentanyl metabolites biotransformation pathways the liver and brain of zebrafish HR-MS |
| url | https://www.frontiersin.org/articles/10.3389/fphar.2023.1325932/full |
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