Velez A, Papsun DM, Scott KS, Krotulski AJ
Journal of Forensic ScienceNovel synthetic opioid (NSO) continue to emerge in the United States in the midst of an opioid crisis. The NSO 2F-viminol was identified in casework at the Center for Forensic Science Research and Education through its NPS Discovery program in 2019. Little information and published literature were available for this new opioid at the time. To address this, human liver microsomes (HLMs) were used to perform in vitro metabolism studies with a drug standard. The goal was to predict in vivo metabolism.
Experimental samples were prepared using HLMs, NADPH, phosphate buffer (pH 7.4), and a 2F-viminol standard. Standard samples were prepared containing only drug, control samples were prepared with drug and HLMs but no NADPH cofactor, and metabolism reaction mixtures contained drug, HLMs and NADPH. The subsequent mixtures were incubated with light shaking to allow metabolism to occur. After cleanup, metabolite mixtures were analyzed via a SCIEX TripleTOF 5600+ liquid chromatograph quadrupole-time-of-flight mass spectrometer (LC-QTOF-MS). The generated metabolic structures were elucidated using SCIEX MetabolitePilot software (version 2.0). In addition to remaining parent drug, seven metabolites of 2F-viminol were discovered, including N-dealkylated and hydroxylated species.
The proposed primary metabolites of 2F-viminol were N-dealkylation (sec-butyl) + hydroxylation and N-dealkylation (sec-butyl); however, they should be confirmed in authentic samples, and forensic laboratories should consider adding 2F-viminol and its metabolites to screening protocols to help in extending the window of detection for the parent drug in toxicological samples. As NSOs continue to appear, forensic laboratories must continue metabolism experiments to generate information about pharmacokinetics.
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