202859-39-0Relevant articles and documents
Metabolism of butyrylfentanyl in fresh human hepatocytes: Chemical synthesis of authentic metabolite standards for definitive identification
Kanamori, Tatsuyuki,Iwata, Yuko Togawa,Segawa, Hiroki,Yamamuro, Tadashi,Kuwayama, Kenji,Tsujikawa, Kenji,Inoue, Hiroyuki
, p. 623 - 630 (2019/05/08)
The metabolism of butyrylfentanyl, a new designer drug, was investigated using fresh human hepatocytes isolated from a liver-humanized mouse model. In the culture medium of hepatocytes incubated with butyrylfentanyl, the desphenethylated metabolite (nor-butyrylfentanyl), w-hydroxy-butyrylfentanyl, (w-1)-hydroxy-butyrylfentanyl, 4′-hydroxy-butyrylfentanyl, β-hydroxy-butyrylfentanyl, 4′-hydroxy-3′- methoxy-butyrylfentanyl, and w-carboxy-fentanyl were identified as the metabolites of butyrylfentanyl. Each metabolite was definitively identified by comparing the analytical data with those of authentic standards. The amount of the main metabolite, nor-butyrylfentanyl, reached 37% of the initial amount of butyrylfentanyl at 48 h. W-Hydroxy-butyrylfentanyl and (w-1)-hydroxy-butyrylfentanyl, formed by hydroxylation at the Nbutyryl group of butyrylfentanyl, were the second and third largest metabolites, respectively. The majority of 4′-hydroxy-butyrylfentanyl and 4′-hydroxy-3′-methoxy-butyrylfentanyl was considered to be conjugated. CYP reaction phenotyping for butyrylfentanyl using human liver microsomes and various anti-CYP antibodies revealed that CYP3A4 was involved in the formation of nor-butyrylfentanyl, (w-1)-hydroxybutyrylfentanyl, and β-hydroxy-butyrylfentanyl. In contrast, CYP2D6 was involved in the formation of w-hydroxy-butyrylfentanyl.
