Metabolism of the Synthetic Cathinone Alpha-Pyrrolidinoisohexanophenone in Humans Using UHPLC--MS-QToF.

This article focuses on the metabolic profiling of alpha-pyrrolidinoisohexanophenone (α-PiHP), a synthetic cathinone structurally related to α-PHP and considered an analog of α-PVP, a Schedule I drug under the United Nations Convention on Psychotropic Substances. Using in vitro human liver microsome (pHLM) and S9 fraction (pS9) incubations alongside in vivo urine samples from users, ten urinary metabolites of α-PiHP were tentatively identified and characterized via liquid chromatography–high-resolution mass spectrometry. The study found that five metabolites, including those formed by keto moiety reduction and combined pyrrolidine ring oxidation with aliphatic hydroxylation, were more abundant in urine than the parent compound, highlighting their importance as biomarkers for confirming α-PiHP consumption. The proposed metabolic pathways involve keto reduction, aliphatic hydroxylation, pyrrolidine ring oxidation or ring-opening followed by carboxylation, and their combinations. These findings emphasize the necessity of detecting specific metabolites alongside the parent drug to reliably identify α-PiHP intake, especially given the analytical challenges posed by structurally similar compounds.