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

Area of Science:

• Forensic Toxicology
• Pharmacology
• Analytical Chemistry

Background:

• Alpha-pyrrolidinoisohexanophenone (α-PiHP) is a synthetic cathinone, structurally related to cathine and an analog of α-PVP.
• α-PiHP emerged in Europe in 2016 and saw increased prevalence in Hungary by 2021.
• Understanding α-PiHP metabolism is crucial for forensic identification and toxicological analysis.

Purpose of the Study:

• To identify and characterize the in vitro and in vivo metabolites of α-PiHP.
• To establish a comprehensive metabolic profile of α-PiHP in human biological samples.

Main Methods:

• Metabolite identification using human liver microsomes (pHLM) and S9 fractions (pS9).
• Analysis of urine samples from control and α-PiHP users.
• Liquid chromatography coupled with high-resolution mass spectrometry (LC-HRMS) for metabolite detection.

Main Results:

• Ten in vivo urinary metabolites of α-PiHP were tentatively identified and confirmed in vitro.
• Five metabolites were more abundant than the parent compound in urine.
• Major metabolites included keto reduction products (M01) and pyrrolidine ring oxidation with hydroxylation and keto reduction (M06).

Conclusions:

• The study elucidated the metabolic pathways of α-PiHP in humans.
• Identified metabolites provide valuable targets for the detection of α-PiHP use in biological samples.
• Metabolic profiling aids in understanding the pharmacokinetics and toxicological profile of this emerging synthetic cathinone.