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In vitro metabolite...
In vitro metabolite identification of acetylbenzylfentanyl, benzoylbenzylfentanyl, 3-fluoro-methoxyacetylfentanyl, and 3-phenylpropanoylfentanyl using LC-QTOF-HRMS together with synthesized references
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- Rautio, Tobias (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Vangerven, Daan (author)
- Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden
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- Dahlén, Johan, 1969- (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Watanabe, Shimpei (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden; RIKEN SPring 8 Ctr, Japan
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- Kronstrand, Robert, 1966- (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden
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- Vikingsson, Svante, 1983- (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden; RTI Int, NC USA
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- Konradsson, Peter, 1957- (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Wu, Xiongyu, 1972- (author)
- Linköpings universitet,Kemi,Tekniska fakulteten
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- Gréen, Henrik, 1975- (author)
- Linköpings universitet,Avdelningen för klinisk kemi och farmakologi,Medicinska fakulteten,Natl Board Forens Med, Dept Forens Genet & Forens Toxicol, Linkoping, Sweden
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(creator_code:org_t)
- 2023-02-19
- 2023
- English.
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In: Drug Testing and Analysis. - : WILEY. - 1942-7603 .- 1942-7611. ; 15:7, s. 711-729
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https://liu.diva-por... (primary) (Raw object)
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https://urn.kb.se/re...
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https://doi.org/10.1...
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Abstract
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- Acetylbenzylfentanyl, benzoylbenzylfentanyl, 3-fluoro-methoxyacetylfentanyl, and 3-phenylpropanoylfentanyl are fentanyl analogs that have been reported to the European Monitoring Centre for Drugs and Drug Addiction in recent years. The aim of this study was to identify metabolic pathways and potential biomarker metabolites of these fentanyl analogs. The compounds were incubated (5 mu M) with cryopreserved hepatocytes for up to 5 h in vitro. Metabolites were analyzed with liquid chromatography-quadrupole time of flight-high-resolution mass spectrometry (LC-QTOF-HRMS). The experiments showed that acetylbenzylfentanyl, benzoylbenzylfentanyl, and 3-phenylpropanoylfentanyl were mainly metabolized through N-dealkylation (forming nor-metabolites) and 3-fluoro-methoxyacetylfentanyl mainly through demethylation. Other observed metabolites were formed by mono-/dihydroxylation, dihydrodiol formation, demethylation, dehydrogenation, amide hydrolysis, and/or glucuronidation. The experiments showed that a large number of metabolites of 3-phenylpropanoylfentanyl were formed. The exact position of hydroxy groups in formed monohydroxy metabolites could not be established solely based upon recorded MSMS spectra of hepatocyte samples. Therefore, potential monohydroxy metabolites of 3-phenylpropanoylfentanyl, with the hydroxy group in different positions, were synthesized and analyzed together with the hepatocyte samples. This approach could reveal that the beta position of the phenylpropanoyl moiety was highly favored; beta-OH-phenylpropanoylfentanyl was the most abundant metabolite after the nor-metabolite. Both metabolites have the potential to serve as biomarkers for 3-phenylpropanoylfentanyl. The nor-metabolites of acetylbenzylfentanyl, benzoylbenzylfentanyl, and 3-fluoro-methoxyacetylfentanyl do also seem to be suitable biomarker metabolites, as do the demethylated metabolite of 3-fluoro-methoxyacetylfentanyl. Identified metabolic pathways and formed metabolites were in agreement with findings in previous studies of similar fentanyl analogs.
Subject headings
- MEDICIN OCH HÄLSOVETENSKAP -- Medicinska och farmaceutiska grundvetenskaper -- Farmaceutiska vetenskaper (hsv//swe)
- MEDICAL AND HEALTH SCIENCES -- Basic Medicine -- Pharmaceutical Sciences (hsv//eng)
Keyword
- fentanyl analogs; hepatocytes; metabolite synthesis; new psychoactive substances
Publication and Content Type
- ref (subject category)
- art (subject category)
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- By the author/editor
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Rautio, Tobias
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Vangerven, Daan
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Dahlén, Johan, 1 ...
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Watanabe, Shimpe ...
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Kronstrand, Robe ...
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Vikingsson, Svan ...
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Konradsson, Pete ...
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Wu, Xiongyu, 197 ...
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Gréen, Henrik, 1 ...
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- About the subject
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- MEDICAL AND HEALTH SCIENCES
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MEDICAL AND HEAL ...
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and Basic Medicine
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and Pharmaceutical S ...
- Articles in the publication
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Drug Testing and ...
- By the university
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Linköping University