Identification of phase I and II metabolites of the new designer drug α-pyrrolidinohexiophenone (α-PHP) in human urine by liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS).
Pyrrolidinophenones represent one emerging class of newly encountered drugs of abuse, also known as 'new psychoactive substances', with stimulating psychoactive effects. In this work, we report on the detection of the new designer drug α-pyrrolidinohexiophenone (α-PHP) and its phase I and II metabolites in a human urine sample of a drug abuser. Determination and structural elucidation of these metabolites have been achieved by liquid chromatography electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS). By tentative identification, the exact and approximate structures of 19 phase I metabolites and nine phase II glucuronides were elucidated. Major metabolic pathways revealed the reduction of the ß-keto moieties to their corresponding alcohols, didesalkylation of the pyrrolidine ring, hydroxylation and oxidation of the aliphatic side chain leading to n-hydroxy, aldehyde and carboxylate metabolites, and oxidation of the pyrrolidine ring to its lactam followed by ring cleavage and additional hydroxylation, reduction and oxidation steps and combinations thereof. The most abundant phase II metabolites were glucuronidated ß-keto-reduced alcohols. Besides the great number of metabolites detected in this sample, α-PHP is still one of the most abundant ions together with its ß-keto-reduced alcoholic dihydro metabolite. Monitoring of these metabolites in clinical and forensic toxicology may unambiguously prove the abuse of the new designer drug α-PHP.
Department of Toxicology and Forensic Toxicology, Synlab MVZ Weiden GmbH, Weiden, Germany.
Michael
M
Paul
Department of Toxicology and Forensic Toxicology, Synlab MVZ Weiden GmbH, Weiden, Germany.
Sergej
S
Bleicher
Department of Toxicology and Forensic Toxicology, Synlab MVZ Weiden GmbH, Weiden, Germany.
Susanne
S
Guber
Department of Toxicology and Forensic Toxicology, Synlab MVZ Weiden GmbH, Weiden, Germany.
Josef
J
Ippisch
Department of Public Health, University of Verona, Policlinico Borgoroma, Verona, Italy.
Aldo
A
Polettini
Department of Toxicology and Forensic Toxicology, Synlab MVZ Weiden GmbH, Weiden, Germany.
Wolfgang
W
Schultis
D002853:Chromatography, Liquid / Q000379:methods*; D015198:Designer Drugs / Q000378:metabolism* / Q000493:pharmacokinetics; D006801:Humans; D015394:Molecular Structure; D011759:Pyrrolidines / Q000378:metabolism* / Q000652:urine*; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
D015198:Designer Drugs; D011759:Pyrrolidines; C000609812:alpha-pyrrolidinohexiophenone
fragmentation pathways; liquid-chromatography electrospray ionisation quadrupole time-of-flight mass spectrometry (LC-ESI-QTOF-MS); new psychoactive substances (NPS); phase I and II metabolites; α-pyrrolidinohexiophenone (α-PHP)