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Metabolism of a new synthetic opioid tetrahydrofuranylfentanyl in fresh isolated human hepatocytes: Detection and confirmation of ring‐opened metabolites
Author(s) -
Kanamori Tatsuyuki,
Segawa Hiroki,
Yamamuro Tadashi,
Kuwayama Kenji,
Tsujikawa Kenji,
Iwata Yuko T.
Publication year - 2020
Publication title -
drug testing and analysis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 54
eISSN - 1942-7611
pISSN - 1942-7603
DOI - 10.1002/dta.2743
Subject(s) - metabolite , chemistry , tetrahydrofuran , epoxide , metabolism , ring (chemistry) , carboxylic acid , fentanyl , alcohol , stereochemistry , biochemistry , organic chemistry , pharmacology , catalysis , biology , solvent
The metabolism of a new synthetic opioid tetrahydrofuranylfentanyl (THF‐fentanyl) was investigated using fresh human hepatocytes. Fourteen metabolites of THF‐fentanyl, such as tetrahydrofuran ring‐opened metabolites, desphenethylated metabolites, hydroxylated metabolites, and hydroxylated and methoxylated metabolites and their glucuronides, were detected in the culture medium of hepatocytes incubated with THF‐fentanyl. Six metabolites, i.e. desphenethylated metabolite, 4′‐hydroxy‐THF‐fentanyl, β‐hydroxy‐THF‐fentanyl, 4′‐hydroxy‐3′‐methoxy‐THF‐fentanyl, ring‐opened alcohol metabolite, and ring‐opened carboxylic acid metabolite, were identified via chemically synthesized authentic standards. A ring‐opened alcohol metabolite and a ring‐opened carboxylic acid metabolite are thought to be formed by reduction or oxidation of the intermediate aldehyde, which was formed by ring‐opening of the metabolite hydroxylated at the carbon atom adjacent to the oxygen atom of the tetrahydrofuran ring. A ring‐opened carboxylic acid metabolite was the main metabolite of THF‐fentanyl based on the peak intensity.