In vitro Characterization of NPS Metabolites Produced by Human Liver Microsomes and the HepaRG Cell Line Using Liquid Chromatographyhigh Resolution Mass Spectrometry (LC-HRMS) Analysis: Application to Furanyl Fentanyl
Objective: This work aims to investigate and compare metabolites of Fu-F using two in vitro experimental approaches.
Methods: CYP- and UGT-dependent metabolites of Fu-F were investigated by means of analyses of both human liver microsome (HLM) and hepatic (HepaRG) cell line incubates using liquid chromatography with high-resolution mass detection and, subsequently, compared and confronted to recently published data.
Results: Seventeen Fu-F metabolites were produced and several metabolic pathways can be postulated. HLMs and HepaRG cultures appear to be complementary: HepaRG cells produced 9 additional metabolites, but which appear to be minor in vivo metabolites. Specific* and/or abundant Fu-F metabolites are dihydrodiol-Fu-F*, norFu-F* and despropionylfentanyl. However, norFu-F seems to be inconstantly observed in in vivo cases. Furthermore, a sulfate metabolite presents at significant rate in urine obtained from FU-F users was not identified here, as in another in vitro study.
Conclusion: HLMs represent an acceptable first choice tool for a single NPS metabolism study in forensic laboratories. Dihydrodiol-Fu-F and despropionylfentanyl could be proposed as reliable metabolites to be recorded in HRMS libraries in order to improve detection of Fu-F users. Nevertheless, additional verifications of in vivo data remain necessary to confirm relevant blood and urinary metabolites of Fu-F.
Document Type: Research Article
Publication date: August 1, 2017
This article was made available online on December 8, 2017 as a Fast Track article with title: "In vitro Characterization of NPS Metabolites Produced by Human Liver Microsomes and the HepaRG Cell Line Using Liquid Chromatographyhigh Resolution Mass Spectrometry (LC-HRMS) Analysis: Application to Furanyl Fentanyl".
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