ORCID

0009-0007-4420-9411

Keywords

fentanyl analogs; metabolites; in vitro metabolism

Abstract

The opioid crisis is an ongoing problem in the United States, and fentanyl analogs play a major role in the issue, as novel fentanyl analogs are constantly being developed. Substitutions and additions to the fentanyl scaffold impact the potency of the substances and can sometimes influence the biotransformation of the drugs. In an investigation of eleven fentanyl analogs, in vitro metabolism via human liver microsomes revealed similarities between metabolites of certain fentanyl analogs that contained a methoxy substituent. Additionally, a common metabolite was identified between fentanyl analogs that were methoxylated at the para-position. Other common metabolites were noted between analogs which contain a single additional methyl group anywhere other than the phenylethyl moiety of the fentanyl scaffold, between analogs with no changes to the amide and N-phenyl moieties, and between certain analogs which were either singly methylated or both methylated and methoxylated. These findings indicate that the major pathway for metabolism of methoxylated fentanyl analogs is largely consistent, regardless of the location of the methoxy substituent so long as the piperidine nitrogen is unobstructed to be available for N-dealkylation. For fentanyl analogs that are methylated, norfentanyl-like metabolites were also observed. For fentanyl analogs that contain an alteration to the aromatic moieties, only one metabolite was found to be in common between two of the investigated analogs that were not isomers. Investigating the commonalities between the metabolite profiles of methoxylated fentanyl analogs provides a valuable insight to potentially identify new ways for toxicologists to gather structural information about novel fentanyl analogs.

Completion Date

2026

Semester

Spring

Committee Chair

Bridge, Candice

Degree

Doctor of Philosophy (Ph.D.)

College

College of Sciences

Department

Chemistry

Format

PDF

Document Type

Dissertation

Identifier

DP0053270

Release Date

5-15-2028

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Available for download on Monday, May 15, 2028

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