Metabolites to parent 3-MeO-PCP ratio in human urine collected in two fatal cases.

Two fatal overdoses involving the dissociative drug 3-methoxyphencyclidine (3-MeO-PCP) are described. The compound, a new psychoactive substance in the phencyclidine family, has been proposed as a legal alternative to phencyclidine in some countries. Using mass spectrometry, the authors detected 3-MeO-PCP and its metabolites in human urine. In vitro metabolism studies with human liver microsomes identified four metabolites: O-demethyl-3-MeO-PCP, piperidine-hydroxy-3-MeO-PCP, O-demethyl-piperidine-di-hydroxy-3-MeO-PCP, and piperidine-di-hydroxy-3-MeO-PCP. All were found in the urine of both cases. The ratio of each metabolite to parent 3-MeO-PCP was always less than 1, indicating that testing for metabolites does not extend the detection window for the drug.

Study at a glance

Abstract

In this article, two fatal cases related to the use of 3-methoxyphencyclidine (3-MeO-PCP) are described. This compound is a new psychoactive substance that belongs to the phencyclidine family. In the recent period, this dissociative drug has gained interest because of its proposal as a legally available alternative to phencyclidine in some countries. The scientific literature related to 3-MeO-PCP is very poor. Using standard ultra-performance liquid chromatography-mass spectrometry and ultra-performance liquid chromatography-tandem mass spectrometry, the authors focused on the detection of 3-MeO-PCP and its metabolites in human urine. 3-MeO-PCP metabolism was studied in vitro after drug incubation with human liver microsomes and the identified metabolites were investigated in the urine of the two forensic cases. 3-MeO-PCP metabolites, including O-demethyl-3-MeO-PCP, piperidine-hydroxy-3-MeO-PCP, O-demethyl-piperidine-di-hydroxy-3-MeO-PCP and piperidine-di-hydroxy-3-MeO-PCP, were detectable in the urine from both cases and the ratio between metabolites and parent 3-MeO-PCP, always lower than 1, were calculated to estimate the proportionality of metabolites. At this stage, one can conclude that testing for 3-MeO-PCP metabolites does not increase the window of detection of the drug.