In vitro and in vivo metabolism of 3-MeO-PCE in human liver microsomes, a zebrafish model, and two human urine samples based on liquid chromatography-high resolution mass spectrometry.

3-Methoxyeticyclidine (3-MeO-PCE), a substance related to phencyclidine (PCP), binds more strongly to NMDA receptors than PCP and has been linked to fatal overdoses. Using zebrafish and human liver microsomes, researchers identified 14 metabolites of 3-MeO-PCE through metabolic pathways including hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, and conjugation. Urine samples from known consumers revealed 3-MeO-PCE and three metabolites. The hydroxylation product, M2, is recommended as a biomarker to confirm 3-MeO-PCE intake in clinical and forensic settings.

Study at a glance

Abstract

3-Methoxyeticyclidine (3-MeO-PCE), a phencyclidine-type substance, has a higher N-methyl-D-aspartate receptor (NMDAR) receptor binding affinity than phencyclidine (PCP) and an involvement in fatal intoxication cases. The aim of this study was to identify new biomarkers and biotransformation pathways for 3-MeO-PCE. In vitro models were established using zebrafish and human liver microsomes for analysis of the phase I and II metabolites of 3-MeO-PCE by liquid chromatography-high resolution mass spectrometry (LC-HRMS). Urine samples of known 3-MeO-PCE consumers in forensic cases were then subjected to analysis. Overall, 14 metabolites were identified in zebrafish and human liver microsomes, allowing postulation of the following metabolic pathways: hydroxylation, O-demethylation, N-dealkylation, dehydrogenation, combination, and glucuronidation or sulfation. 3-MeO-PCE and three metabolites (M2, M3, and M6) were detected in urine. We recommended M2 (the hydroxylation product) as a potential biomarker for documenting 3-MeO-PCE intake in clinical and forensic cases.