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New psychoactive substances 3-methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeO-PCPy): metabolic fate elucidated with rat urine and human liver preparations and their detectability in urine by GC-MS, LC-(high resolution)-MSn, and LC-high resolution-MS/MS

Michely, JA and Manier, SK and Caspar, AT and Brandt, SD and Wallach, J and Maurer, HH (2017) New psychoactive substances 3-methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeO-PCPy): metabolic fate elucidated with rat urine and human liver preparations and their detectability in urine by GC-MS, LC-(high resolution)-MSn, and LC-high resolution-MS/MS. Current Neuropharmacology, 15 (5). pp. 692-712. ISSN 1570-159X

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Abstract

3-Methoxyphencyclidine (3-MeO-PCP) and 3-methoxyrolicyclidine (3-MeO-PCPy) are two new psychoactive substances (NPS). The aims of the present study were the elucidation of their metabolic fate in rat and pooled human liver microsomes (pHLM), the identification of the cytochrome P450 (CYP) isoenzymes involved, and the detectability using standard urine screening approaches (SUSA) after intake of common users’ doses using gas chromatography-mass spectrometry (GC-MS), liquid chromatography-multi-stage mass spectrometry (LC-MSn), and liquid chromatography-high-resolution tandem mass spectrometry (LC-HR-MS/MS). For metabolism studies, rat urine samples were treated by solid phase extraction or simple precipitation with or without previous enzymatic conjugate cleavage. After analyses via LC-HR-MSn, the phase I and II metabolites were identified. Both drugs showed multiple aliphatic hydroxylations at the cyclohexyl ring and the heterocyclic ring, single aromatic hydroxylation, carboxylation after ring opening, O-demethylation, and glucuronidation. The transferability from rat to human was investigated by pHLM incubations, where O-demethylation and hydroxylation were observed. The involvement of the individual CYP enzymes in the initial metabolic steps was investigated after single CYP incubations. For 3-MeO-PCP, CYP 2B6 was responsible for aliphatic hydroxylations and CYP 2C19 and CYP 2D6 for O-demethylation. For 3-MeO-PCPy, aliphatic hydroxylation was again catalyzed by CYP 2B6 and O-demethylation by CYP 2C9 and CYP 2D6. As only polymorphically expressed enzymes were involved, pharmacogenomic variations might occur, but clinical data are needed to confirm the relevance. The detectability studies showed that the authors’ SUSAs were suitable for monitoring the intake of both drugs using the identified metabolites.

Item Type: Article
Subjects: R Medicine > RM Therapeutics. Pharmacology
Divisions: Pharmacy & Biomolecular Sciences
Publisher: Bentham Science
Date Deposited: 17 Oct 2016 11:35
Last Modified: 18 Oct 2017 00:50
DOI or Identification number: 10.2174/1570159X14666161018151716
URI: http://researchonline.ljmu.ac.uk/id/eprint/4628

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