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Purpose Recently, the opioid epidemic has become a serious problem, particularly in North America and Europe. The aim of this study was to clarifyQuery the metabolic fate of a new synthetic opioid furanylfentanyl. Methods The metabolism of furanylfentanyl was investigated by incubating fresh human hepatocytes with 10 µM furanylfentanyl at 37 °C for 48 h in an atmosphere of 5% CO 2 . After incubation, the culture medium was deproteinized and analyzed by liquid chromatography/mass spectrometry. Results On the chromatogram, four metabolites of furanylfentanyl were presumably detected: 4´-hydroxy-furanylfentanyl, β-hydroxy-furanylfentanyl, 4´-hydroxy-3´-methoxy-furanylfentanyl, and a ring-opened carboxylic acid metabolite. These newly found metabolites of furanylfentanyl were then definitely identified using chemically synthesized authentic standards. Conclusions Four metabolites of furanylfentanyl were newly identified. Although it has been proposed over recent years that a dihydrodiol metabolite, which has the same molecular weight as the ring-opened carboxylic acid metabolite, is formed from furanylfentanyl, this study demonstrated that the ring-opened carboxylic acid metabolite, rather than the dihydrodiol metabolite, is formed from furanylfentanyl.

Detection and confirmation of the ring-opened carboxylic acid metabolite of a new synthetic opioid furanylfentanyl