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”

doi:10.2174/1570159X14666161018151716

Paper

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”

Published Jul 1, 2017 · Julian A Michely, Sascha K. Manier, A. Caspar

Current Neuropharmacology

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26

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0

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Abstract

Background: 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) Methods: 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 Results: 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 Conclusions: 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

In Vitro Study

Study Snapshot

3-Methoxyphencyclidine and 3-Methoxyrolicyclidine show similar metabolic fates in rats and humans, with CYP enzymes playing key roles in their metabolism, and standard urine screening approaches are suitable for monitoring their intake.

PopulationOlder adults (50-71 years)

Sample size24

MethodsObservational

OutcomesBody Mass Index projections

ResultsSocial networks mitigate obesity in older groups.

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Paper

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”

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Citations

Characterization and Metabolism of Drug Products Containing the Cocaine-Like New Psychoactive Substances Indatraline and Troparil

Indatraline and troparil, similar to cocaine, undergo similar metabolic fates in rat urine, with indatraline forming two phase I and four phase II metabolites and troparil forming four phase I and three phase II metabolites.

Characterization of Extensive 2-Fluorodeschloroketamine (2F-DCK) Metabolism in Pooled Human Liver Microsomes (pHLM), Urine, and Hair from an Addicted Patient Using High-Resolution Accurate Mass (HRAM) Spectrometry.

This study identified 26 putative 2F-DCK metabolites in urine and hair samples from an addict, confirming its reliability as a target analyte and identifying deschloroketamine as a 2F-DCK metabolite in hair.

Characterization of 3-Hydroxyeticyclidine (3-HO-PCE) Metabolism in Human Liver Microsomes and Biological Samples Using High-Resolution Mass Spectrometry

This study identified 15 putative metabolites of 3-HO-PCE, which can extend the detection window for drug users, and identified M2a and hydroxy-PCA as reliable biomarkers for untargeted screening in urine and hair.

Arylcyclohexylamine Derivatives: Pharmacokinetic, Pharmacodynamic, Clinical and Forensic Aspects

Arylcyclohexylamine derivatives, such as ketamine, phencyclidine, and eticyclidine, are rapidly increasing in recreational use, with their pharmacokinetic and pharmacodynamic properties differing from ketamine, posing a significant risk for intoxication.

In Vitro Metabolic Fate of the Synthetic Cannabinoid Receptor Agonists QMPSB and QMPCB (SGT-11) Including Isozyme Mapping and Esterase Activity

QMPSB and QMPCB undergo ester hydrolysis, hydroxylation, and glucuronide formation, which can be used to identify toxicological screening targets and predict drug interactions.