Characterizing metabolites and potential metabolic pathways for the novel psychoactive substance methoxetamine.
E. Menzies, S. Hudson, Paul I Dargan, M. Parkin, David M Wood, A. Kicman
Drug Testing and Analysis June 1, 2014 DOI: 10.1002/dta.1541 (opens in new tab)
Study at a glance
AI-extracted from the abstract| Characteristics | Laboratory study with confirmatory case series Case report Peer reviewed |
|---|---|
| Sample size | 3 |
| Population | Individuals presenting with acute methoxetamine toxicity |
| Key findings | The in vitro metabolism of methoxetamine produced a large number of phase I and II metabolites, and most were confirmed in urine from three cases of acute toxicity, validating the approach for studying NPS metabolism. |
Abstract
The classic approach of controlled volunteer studies to study drug metabolism is difficult or impossible to undertake for novel psychoactive substances (NPS), as there is generally very limited information available to allow appropriate dose finding and safety. A viable and powerful alternative is the identification and characterization of phase I and II metabolites of such drugs by examining the concordance of data gathered from analysis of microsomal incubates with that from analysis of specimens collected from individuals with analytically confirmed use of NPS. Liquid chromatography‐high resolution mass spectrometry provides the ability to reliably identify such metabolites. We used this technique here to study the metabolism of the ketamine analogue methoxetamine. A large number of metabolites were identified in the in vitro studies including normethoxetamine, O‐desmethylmethoxetamine, dihydromethoxetamine, dehydromethoxetamine and several structural isomers of hydroxymethoxetamine and hydroxynormethoxetamine. pH dependent liquid‐liquid extraction was used to discriminate phenolic from alcoholic metabolites. Phase II glucuronide conjugates included those of O‐desmethylmethoxetamine, O‐desmethylnormethoxetamine and O‐desmethylhydroxymethoxetamine. The majority of these phase I and II metabolites were confirmed to be present in urine collected from three individuals presenting with acute methoxetamine toxicity. Copyright © 2013 John Wiley & Sons, Ltd.