Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Correlations between metabolism and structural elements of the alicyclic fentanyl analogs cyclopropyl fentanyl, cyclobutyl fentanyl, cyclopentyl fentanyl, cyclohexyl fentanyl and 2,2,3,3-tetramethylcyclopropyl fentanyl studied by human hepatocytes and LC-QTOF-MS
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences.
Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
Linköping University, Department of Medical and Health Sciences, Division of Drug Research. Linköping University, Faculty of Medicine and Health Sciences. Natl Board Forens Med, Dept Forens Genet and Forens Toxicol, Linkoping, Sweden.
Show others and affiliations
2019 (English)In: Archives of Toxicology, ISSN 0340-5761, E-ISSN 1432-0738, Vol. 93, no 1, p. 95-106Article in journal (Refereed) Published
Abstract [en]

Recently, a number of fentanyl analogs have been implicated in overdose deaths in Europe and in the US. So far, little is known of the molecular behavior of the structurally related subgroup; the alicyclic fentanyls. In this study, reference standards of cyclopropyl, cyclobutyl, cyclopentyl, cyclohexyl, and 2,2,3,3-tetramethylcyclopropyl fentanyl (TMCPF) at a final concentration of 5 mu M were incubated with cryopreserved human hepatocytes (1x10(6) cells/mL) for 0, 1, 3 and 5h. The metabolites formed were identified by liquid chromatography-quadrupole time-of-flight mass spectrometry analysis. The most abundant biotransformation found was N-dealkylation (formation of normetabolites) and oxidation of the alicyclic rings. As ring size increased, the significance of N-dealkylation decreased in favor of alicyclic ring oxidation. An example of this was cyclopropyl fentanyl, with a three-carbon ring, whose normetabolite covered 82% of the total metabolic peak area and no oxidation of the alicyclic ring was observed. In contrast, TMCPF, with a seven-carbon ring structure, rendered as much as 85% of its metabolites oxidized on the alicyclic ring. Other biotransformations found included oxidation of the piperidine ethyl moiety and/or the phenethyl substructure, glucuronidation as well as amide hydrolysis to form metabolites identical to despropionyl fentanyl. Taken together, this study provides a base for understanding the metabolism of a number of structurally related fentanyl analogs formed upon intake.

Place, publisher, year, edition, pages
SPRINGER HEIDELBERG , 2019. Vol. 93, no 1, p. 95-106
Keywords [en]
Fentanyl analogs; Metabolism; Human hepatocytes; LC-QTOF-MS
National Category
Pharmaceutical Sciences
Identifiers
URN: urn:nbn:se:liu:diva-154723DOI: 10.1007/s00204-018-2330-9ISI: 000456388700008PubMedID: 30361799OAI: oai:DiVA.org:liu-154723DiVA, id: diva2:1292263
Note

Funding Agencies|Strategiomradet Forensiska Vetenskaper (Strategic Research Area Forensic Sciences) at Linkoping University; Eurostar project Psychomics

Available from: 2019-02-27 Created: 2019-02-27 Last updated: 2019-03-15

Open Access in DiVA

fulltext(3642 kB)73 downloads
File information
File name FULLTEXT01.pdfFile size 3642 kBChecksum SHA-512
1c214f76c262211ae013a7e9e617c19dda7ad4c3e4346e74249201bbe110ffcd0a9fe014402f2f09978bcf9280a4869e2c0b8fa89585106bd87195a2fc306b1b
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Åstrand, AnnaKronstrand, RobertGreen, HenrikVikingsson, Svante
By organisation
Division of Drug ResearchFaculty of Medicine and Health Sciences
In the same journal
Archives of Toxicology
Pharmaceutical Sciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 73 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

doi
pubmed
urn-nbn

Altmetric score

doi
pubmed
urn-nbn
Total: 93 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf