Metabolic profiling of deschloro‐N‐ethyl‐ketamine and identification of new target metabolites in urine and hair using human liver microsomes and high‐resolution accurate mass spectrometry

Abstract

The aim of this study was to identify new markers of deschloro‐N‐ethyl‐ketamine (O‐PCE), a ketamine analogue that has been involved in acute intoxications with severe outcomes including death and whose metabolism has never been studied before. In vitro study after 2‐h incubation with pooled human liver microsomes (HLMs) cross‐checked by the analysis of urine and hair from a 43‐year‐old O‐PCE user (male) were performed by liquid chromatography–high resolution mass spectrometry (LC‐HRMS). Acquired data were processed by the Compound Discoverer® software, and a full metabolic profile of O‐PCE was proposed. In total, 15 metabolites were identified, 10 were detected in vitro (HLMs) and confirmed in vivo (urine and/or hair), two were present only in HLMs, and the remaining three metabolites were identified only in biological specimens. While O‐PCE was no longer detected in urine, nine metabolites were identified allowing to increase its detection window. In descending order of metabolites abundance, we suggest using 2‐en‐PCA‐N‐Glu (34%, first), M3 (16%, second), O‐PCA‐N‐Glu (15.4%, third), OH‐O‐PCE (15%, fourth) and OH‐PCE (11.9%, fifth) as target metabolites to increase the detection window of O‐PCE in urine. In hair, nine metabolites were identified. OH‐PCA was the major compound (78%) with a relevant metabolite to parent drug ratio (=6) showing its good integration into hair and making it the best marker for long‐term monitoring of O‐PCE exposure.