Citation

Allibe N, Richeval C, Phanithavong M, Faure A, Allorge D, Paysant F, Stanke-Labesque F, Eysseric-Guerin H, Gaulier JM. Drug Test. Anal. 2018; 10(6): 995-1000.

Affiliation

EA 4483 - IMPECS - IMPact de l'Environnement Chimique sur la Santé humaine, University of Lille, F-59000, Lille, France.

Copyright

(Copyright © 2018, John Wiley and Sons)

DOI

10.1002/dta.2326

PMID

29045066

Abstract

New psychoactive substances (NPS) use has rapidly increased over the last decade, and in the last 4 years producers increasingly appear to be targeting non-controlled synthetic opioids, involving fentanyl derivatives such as ocfentanil (OcF). Identification of metabolites is of major importance in the context of NPS use as it could improve detection window in biological matrices in clinical and forensic intoxication cases. Hence, this work aims to report a fatality involving OcF documented by the identification of metabolites. A 30-year-old woman was found dead at home: an unidentified powder was found near her body and some injection sites were found at the autopsy. Toxicological analyses allowed to determine the presence of OcF in the powder, blood (3.7/3.9 μg/L, peripheral/cardiac) and in other post-mortem samples. The most relevant potential CYP- and UGT-dependent metabolites of OcF were investigated in vitro using human liver microsome incubation and liquid chromatography coupled with high resolution mass spectrometry, and subsequently confirmed in post-mortem samples. Four OcF metabolites were produced in vitro (a mono-hydroxylated OcF, O-desmethylOcF, a hydroxylated desmethylOcF and a glucuronidated form of the O-desmethylOcF), and all except the glucuronide were observed in blood and bile post-mortem samples. Considering the relative intensity of the chromatographic peak areas, O-desmethylOcF can be suggested to be an abundant metabolite of OcF. Nevertheless, the relevance of O-desmethylOcF as being a complementary analytical target of OcF for OcF use detection needs further in vivo confirmation, especially through analysis of urines from users.

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Language: en

Keywords

HLMs; LC-HRMS; Ocfentanil; fatality; metabolites