In vitro and in vivo metabolism of 3‐Methoxyeticyclidine in human liver microsomes, a zebrafish model, and two human urine samples based on liquid chromatography–high‐resolution mass spectrometry
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Published:2023-05-09
Issue:1
Volume:16
Page:30-37
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ISSN:1942-7603
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Container-title:Drug Testing and Analysis
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language:en
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Short-container-title:Drug Testing and Analysis
Author:
Xu Linhao12ORCID,
Liu Xinze12,
Song Zixuan12,
Xiang Ping1ORCID,
Hang Taijun2ORCID,
Yan Hui1ORCID
Affiliation:
1. Department of Forensic Toxicology Shanghai Key Laboratory of Forensic Medicine, Academy of Forensic Science Shanghai China
2. School of Pharmacy China Pharmaceutical University Nanjing China
Abstract
Abstract3‐Methoxyeticyclidine (3‐MeO‐PCE), a phencyclidine‐type substance, has a higher N‐methyl‐D‐aspartate receptor binding affinity than phencyclidine and an involvement in fatal intoxication cases. The aim of this study was to identify new biomarkers and biotransformation pathways for 3‐MeO‐PCE. In vitro models were established using zebrafish and human liver microsomes for analysis of the phases I and II metabolites of 3‐MeO‐PCE by liquid chromatography–high‐resolution mass spectrometry. Urine samples of known 3‐MeO‐PCE consumers in forensic cases were then subjected to analysis. Overall, 14 metabolites were identified in zebrafish and human liver microsomes, allowing postulation of the following metabolic pathways: hydroxylation, O‐demethylation, N‐dealkylation, dehydrogenation, combination, and glucuronidation or sulfation. 3‐MeO‐PCE and three metabolites (M2, M3, and M6) were detected in urine. We recommended M2 (the hydroxylation product) as a potential biomarker for documenting 3‐MeO‐PCE intake in clinical and forensic cases.
Funder
National Key Research and Development Program of China
National Natural Science Foundation of China
Science and Technology Commission of Shanghai Municipality
Subject
Spectroscopy,Pharmaceutical Science,Environmental Chemistry,Analytical Chemistry
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