In vitro and in vivo metabolic study of three new psychoactive β-keto-arylcyclohexylamines.

Since the 2000s, more new psychoactive substances have appeared on the illicit drug market. β-Keto-arylcyclohexylamine compounds, which have pharmacological roles in anesthesia, are increasingly used recreationally, but detailed toxicity data are lacking. Analyzing their metabolites can help forensic personnel determine whether someone has taken these illicit substances. This study examined the in vitro and in vivo metabolism of three such compounds: deschloro-N-ethyl-ketamine, fluoro-N-ethyl-ketamine, and bromoketamine. Using zebrafish and human liver microsomes, 49 metabolites were identified via liquid chromatography-high-resolution mass spectrometry. Hydroxy-deschloro-N-ethyl-ketamine, hydroxy-fluoro-N-ethyl-ketamine, and hydroxy-bromoketamine are recommended as biomarkers for documenting intake in clinical and forensic cases.

Study at a glance

Abstract

Since the 2000s, an increasing number of new psychoactive substances have appeared on the illicit drug market. β-Keto-arylcyclohexylamine compounds play important pharmacological roles in anesthesia; however, because these new psychoactive substances have rapidly increasing illicit recreational use, the lack of detailed toxicity data are of particular concern. Therefore, analysis of their metabolites can help forensic personnel provide references and suggestions on whether a suspect has taken an illicit new psychoactive β-keto-arylcyclohexylamine. The present study investigated the in vitro and in vivo metabolism and metabolites of three β-keto-arylcyclohexylamines: deschloro-N-ethyl-ketamine, fluoro-N-ethyl-ketamine and bromoketamine. In vitro and in vivo models were established using zebrafish and human liver microsomes for analysis of Phase I and Phase II metabolites by liquid chromatography-high-resolution mass spectrometry. Altogether, 49 metabolites were identified. The results were applied for the subject urine samples of known fluoro-N-ethyl-ketamine consumer screen analysis in forensic cases. Hydroxy-deschloro-N-ethyl-ketamine, hydroxy-fluoro-N-ethyl-ketamine and hydroxy-bromoketamine were recommended as potential biomarkers for documenting intake in clinical and forensic cases.