Metabolite Profiling of Ortho-, Meta- and Para-Fluorofentanyl by Hepatocytes and High-Resolution Mass Spectrometry

↓ Direkt till sidans innehåll
↓ Direkt till sidans sekundära innehåll (sidomenyn)

Search: WFRF:(Green Henrik 1975 ) > Metabolite Profilin...

Metabolite Profiling of Ortho-, Meta- and Para-Fluorofentanyl by Hepatocytes and High-Resolution Mass Spectrometry

Gundersen, Per Ole M. (author): Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Åstrand, Anna (author): Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten

Gréen, Henrik, 1975- (author): Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden

Josefsson, Martin, 1967- (author): Linköpings universitet,Kemi,Tekniska fakulteten,National Forensic Centre, Drug Unit, Linköping, Sweden

Spigset, Olav (author): Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway

Vikingsson, Svante, 1983- (author): Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden

show less...

Department of Clinical Pharmacology, St Olav University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway Avdelningen för läkemedelsforskning (creator_code:org_t)

2019-11-29
2020
English.
In: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 44:2, s. 140-148

Related links:: https://doi.org/10.1...; show more...; https://liu.diva-por... (primary) (Raw object); https://academic.oup...; https://urn.kb.se/re...; https://doi.org/10.1...; show less...

Journal article (peer-reviewed)

Abstract Subject headings

New psychoactive substances are emerging on the illegal drug market. Synthetic opioids including fentanyl analogues are of special concern due to their high potency. This indicates the possibility of low drug concentrations in vivo and calls for sensitive analytical methods and identification of the most appropriate analytical targets. In this study the in vitro metabolism of ortho-, meta- and para-fluorofentanyl, three fluorinated derivatives of fentanyl, has been investigated using human hepatocytes and compared to the results from an authentic human urine sample. Based on knowledge on the metabolism of similar fentanyl analogues N-dealkylation and hydroxylation was hypothesized to be the most central pathways. The three fluorofentanyl isomers were incubated with pooled human hepatocytes at 1, 3 and 5 h. Liquid chromatography quadrupole time of flight mass spectrometry operating in data-dependent mode was used to analyse the hepatocyte samples, as well as the hydrolysed and non-hydrolysed authentic urine sample. Data were analysed by a targeted approach with a database of potential metabolites. The major metabolite formed in vitro was the N-dealkylation product norfluorofentanyl. In addition various hydroxylated metabolites, a N-oxide, dihydrodiol metabolites and a hydroxymethoxy metabolite were found. In total, 14 different metabolites were identified for each fluorofentanyl isomer. In the authentic urine sample, three metabolites were detected in addition to the ortho-fluorofentanyl parent compound, with hydroxymethoxy metabolite having the highest abundance followed by norfluorofentanyl and a metabolite hydroxylated on the ethylphenyl ring. This in vitro study showed that the metabolic pattern for ortho-, meta-, and para-fluorofentanyl was close to those previously reported for other fentanyl analogues. We suggest that the hydroxymethoxy metabolite and the metabolite hydroxylated on the ethylphenyl ring should be the metabolites primarily investigated in further studies to determine the most appropriate marker for intake of fluorofentanyl derivatives in urine drug screening for human subjects.

Subject headings

MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)

Keyword

Fluorofentanyl; high-resolution mass spectrometry; human hepatocytes; metabolism

Publication and Content Type

ref (subject category)
art (subject category)

Find in a library

Journal of Analytical Toxicology (Search for host publication in LIBRIS)

To the university's database

Find more in SwePub

By the author/editor: Gundersen, Per O ...; Åstrand, Anna; Gréen, Henrik, 1 ...; Josefsson, Marti ...; Spigset, Olav; Vikingsson, Svan ...

About the subject

MEDICAL AND HEALTH SCIENCES: MEDICAL AND HEAL ...; and Basic Medicine; and Pharmacology and ...

Articles in the publication: Journal of Analy ...

By the university: Linköping University

Search outside SwePub

Extend your search to:: Google; Google Book Search; Google Scholar

Kungliga biblioteket hanterar dina personuppgifter i enlighet med EU:s dataskyddsförordning (2018), GDPR. Läs mer om hur det funkar här.
Så här hanterar KB dina uppgifter vid användning av denna tjänst.

LIBRIS.kb.se