4-Methoxy-α-PVP: in silico prediction, metabolic stability, and metabolite identification by human hepatocyte incubation and high-resolution mass spectrometry

Forensic Toxicology
Kayla N EllefsenMarilyn A Huestis

Abstract

Novel psychoactive substances are continuously developed to circumvent legislative and regulatory efforts. A new synthetic cathinone, 4-methoxy-α-PVP, was identified for the first time in illegal products; however, the metabolism of this compound is not known. Complete metabolic profiles are needed for these novel psychoactive substances to enable identification of their intake and to link adverse effects to the causative agent. This study assessed 4-methoxy-α-PVP metabolic stability with human liver microsomes (HLMs) and identified its metabolites after HLM and hepatocyte incubations followed by high-resolution mass spectrometry (HRMS). A Thermo QExactive high-resolution mass spectrometer (HRMS) was used with full scan data-dependent mass spectrometry, with (1) and without (2) an inclusion list of predicted metabolite, and with full scan and all-ion fragmentation (3) to identify potential unexpected metabolites. In silico predictions were performed and compared to in vitro results. Scans were thoroughly mined with different data processing algorithms using WebMetabase (Molecular Discovery). 4-Methoxy-α-PVP exhibited a long half-life of 79.7 min in HLM, with an intrinsic clearance of 8.7 µL min(-1) mg(-1). In addition, this com...Continue Reading

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Citations

Jan 27, 2016·The AAPS Journal·Xingxing DiaoMarilyn A Huestis
May 18, 2016·Analytical and Bioanalytical Chemistry·Madeleine J SwortwoodMarilyn A Huestis
Jul 3, 2016·Archives of Toxicology·H H Maurer, Markus R Meyer
Nov 22, 2018·Drug Testing and Analysis·Katharina Elisabeth GrafingerWolfgang Weinmann
Aug 30, 2020·Journal of Analytical Toxicology·Serena MestriaSabina Strano Rossi
Mar 14, 2017·Forensic Toxicology·Xingxing DiaoMarilyn A Huestis
Oct 3, 2020·Journal of Separation Science·Szymon Ulenberg, Tomasz Bączek
Jan 1, 2021·International Journal of Molecular Sciences·Jeremy CarlierMarilyn A Huestis
Jul 2, 2019·Acta Pharmaceutica : a Quarterly Journal of Croatian Pharmaceutical Society and Slovenian Pharmaceutical Society, Dealing with All Branches of Pharmacy and Allied Sciences·Karolina SłoczyńskaElżbieta Pękala

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Methods Mentioned

BETA
urine collection

Software Mentioned

WebMetaBase
MetaSite

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