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In Vitro Metabolism of Desomorphine

NCJ Number
253445
Journal
Forensic Science International Volume: 289 Dated: August 2018 Pages: 140-149
Author(s)
Jessica Winborn; Donovan Haines; Sarah Kerrigan
Date Published
August 2018
Length
10 pages
Annotation

The goal of this study was to contribute further knowledge regarding the metabolism of desomorphine, the principal pharmacologically active opioid in Krokodil, a homemade injectable drug that is perceived to be a cheaper alternative to heroin.

Abstract

Recombinant human cytochrome P450 enzymes (rCYPs) and recombinant uridine 5ft-diphospho-glucuronosyltransferases (rUGTs) were used to investigate the biotransformational pathways involved. Samples were analyzed by liquid chromatography/quadrupole-time of flight-mass spectrometry (LC-Q/TOF-MS). Seven rCYP (rCYP2B6, rCYP2C8, rCYP2C9, rCYP2C18, rCYP2C19, rCYP2D6 and rCYP3A4) enzymes were found to contribute to desomorphine metabolism and eight phase I metabolites were identified, including nordesomorphine, desomorphine-N-oxide, norhydroxydesomorphine, and five hydroxylated species. Inhibition assays were used to confirm individual rCYP isoenzyme activity. Nine rUGTs (rUGT1A1, rUGT1A3, rUGT1A8, rUGT1A9, rUGT1A10, rUGT2B4, rUGT2B7, rUGT2B15, and rUGT2B17) were found to contribute to the formation of desomorphine-glucuronide. (publisher abstract modified)