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Metabolite Profilin...
Metabolite Profiling of Ortho-, Meta- and Para-Fluorofentanyl by Hepatocytes and High-Resolution Mass Spectrometry
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- Gundersen, Per Ole M. (författare)
- Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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- Åstrand, Anna (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten
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- Gréen, Henrik, 1975- (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden
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- Josefsson, Martin, 1967- (författare)
- Linköpings universitet,Kemi,Tekniska fakulteten,National Forensic Centre, Drug Unit, Linköping, Sweden
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- Spigset, Olav (författare)
- Department of Clinical Pharmacology, St. Olav University Hospital, Trondheim, Norway; Department of Clinical and Molecular Medicine, Norwegian University of Science and Technology, Trondheim, Norway
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- Vikingsson, Svante, 1983- (författare)
- Linköpings universitet,Avdelningen för läkemedelsforskning,Medicinska fakulteten,Department of Forensic Genetics and Forensic Toxicology, National Board of Forensic Medicine, Linköping, Sweden
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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
- Engelska.
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Ingår i: Journal of Analytical Toxicology. - : Oxford University Press. - 0146-4760 .- 1945-2403. ; 44:2, s. 140-148
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Abstract
Ämnesord
Stäng
- 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.
Ämnesord
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmakologi och toxikologi (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmacology and Toxicology (hsv//eng)
Nyckelord
- Fluorofentanyl; high-resolution mass spectrometry; human hepatocytes; metabolism
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
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