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dc.contributor.authorGundersen, Per Ole Mobråten
dc.contributor.authorÅstrand, Anna
dc.contributor.authorGréen, Henrik
dc.contributor.authorJosefsson, Martin
dc.contributor.authorSpigset, Olav
dc.contributor.authorVikingsson, Svante
dc.date.accessioned2020-03-20T11:14:57Z
dc.date.available2020-03-20T11:14:57Z
dc.date.created2019-12-02T15:49:13Z
dc.date.issued2019
dc.identifier.issn0146-4760
dc.identifier.urihttps://hdl.handle.net/11250/2647800
dc.description.abstractNew 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.en_US
dc.language.isoengen_US
dc.publisherOxford University Press (OUP)en_US
dc.rightsNavngivelse-Ikkekommersiell 4.0 Internasjonal*
dc.rights.urihttp://creativecommons.org/licenses/by-nc/4.0/deed.no*
dc.titleMetabolite profiling of ortho-, meta- and para-fluorofentanyl by hepatocytes and high-resolution mass spectrometryen_US
dc.typePeer revieweden_US
dc.typeJournal articleen_US
dc.description.versionpublishedVersionen_US
dc.source.journalJournal of Analytical Toxicologyen_US
dc.identifier.cristin1755620
dc.description.localcode© 2019 The Authors. Published by Oxford University Press. This is an open access article under the CC-BY-NC 4.0 license (http://creativecommons.org/licenses/by-nc/4.0/)en_US
cristin.unitcode194,65,15,0
cristin.unitcode1920,0,0,0
cristin.unitnameInstitutt for klinisk og molekylær medisin
cristin.unitnameSt. Olavs Hospital HF
cristin.ispublishedtrue
cristin.fulltextoriginal
cristin.qualitycode1


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Navngivelse-Ikkekommersiell 4.0 Internasjonal
Except where otherwise noted, this item's license is described as Navngivelse-Ikkekommersiell 4.0 Internasjonal