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)

Abstract

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.

Different in vitro and in vivo tools for elucidating the human metabolism of alpha‐cathinone‐derived drugs of abuse

“…32 Dihydro metabolites formed by reduction of the alpha-keto group detected in PHH incubations 11,15,16,18 could not be found in the pS9 incubations, which is consistent with results reported in previous studies. 32 Dihydro metabolites formed by reduction of the alpha-keto group detected in PHH incubations 11,15,16,18 could not be found in the pS9 incubations, which is consistent with results reported in previous studies.…”

“…This is in accordance to Richter et al, comparing different in vitro models for 4-methoxy-alpha-pyrrolidinovalerophenone. 16 At least all results from in vitro models should be confirmed by authentic human urine. This is in accordance with urine findings for alpha-PHP and alpha-PVT.…”

“…11,[15][16][17][18][19] In addition, the kinetic parameters of CYP isoforms involved in the metabolism were determined for assessing hepatic clearances and to predict possible individual variations in drug elimination or the risk of drug-drug or drug-food interactions. The results were then compared with published results obtained from pHLM, PHH, and authentic human urine samples.…”

Identification and characterization of vilazodone metabolites in rats and microsomes by ultrahigh‐performance liquid chromatography/quadrupole time‐of‐flight tandem mass spectrometry

“…The relative percent abundance for VLZ and each metabolite (M1–M12) formed in urine, faeces and plasma are summarized in Figures a–c. As the metabolism studies were conducted without any reference standards, there may be uncertainty regarding the estimation of metabolites and therefore ion counts have been utilized to carry out semi‐quantitative estimation of metabolites . Based on the present study, it was observed that VLZ was found in all in vivo samples and in comparatively higher percent in faeces (13.93%).…”

Identification and characterization of fluvastatin metabolites in rats by UHPLC/Q‐TOF/MS/MS and in silico toxicological screening of the metabolites

“…So comprehensive study of biotransformation pathways and the knowledge of the possible toxicity of metabolites are prerequisite for the drug discovery and development . Over the years, liquid chromatography–electrospray ionization tandem mass spectrometry (LC–ESI/MS/MS) in combination with accurate mass measurements has been widely used for the identification and characterization of metabolites …”