Metabolism of the designer drug α-pyrrolidinobutiophenone (α-PBP) in humans: Identification and quantification of the phase I metabolites in urine

Urinary phase I metabolites of alpha-pyrrolidinobutiophenone (alpha-PBP) in humans were investigated by analyzing urine specimens obtained from drug abusers. Unequivocal identification and accurate quantification of major metabolites were realized using gas chromatography-mass spectrometry and liquid chromatography-tandem mass spectrometry with newly synthesized authentic standards. Two major phase I metabolic pathways were revealed: (1) reduction of the ketone group to 1-phenyl-2-(pyrrolidin-1-yl)butan-1-ol (OH-alpha-PBP, diastereomers) partly followed by conjugation to its glucuronide and (2) oxidation at the 2 ''-position of the pyrrolidine ring to alpha-(2 ''-oxo-pyrrolidino)butiophenone (2 ''-oxo-alpha-PBP) via the putative intermediate alpha-(2 ''-hydroxypyrrolidino)butiophenone (2 ''-OH-alpha-PBP). Of the phase I metabolites retaining the structural characteristics of the parent drug, OH-alpha-PBP was the most abundant in all specimens examined. Comparison of the phase I metabolism of alpha-PBP and alpha-pyrrolidinovalerophenone (alpha-PVP) suggested a relationship between the aliphatic side chain length and the metabolic pathways in alpha-pyrrolidinophenones: the shorter aliphatic side chain (1) led to more extensive metabolism via reduction of the ketone group than via the oxidation at the 2 ''-position of the pyrrolidine ring and (2) influenced the isomeric ratio of a pair of diastereomers. (C) 2015 Elsevier Ireland Ltd. All rights reserved.