Structural Elucidation of Metabolites of Synthetic Cannabinoid UR-144 by Cunninghamella elegans Using Nuclear Magnetic Resonance (NMR) Spectroscopy

Watanabe, S; Kuzhiumparambil, U; Fu, S

Structural Elucidation of Metabolites of Synthetic Cannabinoid UR-144 by Cunninghamella elegans Using Nuclear Magnetic Resonance (NMR) Spectroscopy

Watanabe, S

Kuzhiumparambil, U

Fu, S

Permalink

Publication Type:: Journal Article
Citation:: AAPS Journal, 2018, 20 (2)
Issue Date:: 2018-03-01

Open Access

Copyright Clearance Process

Recently Added
In Progress
Open Access

This item is open access.

Adobe PDF

Download Accepted Manuscript VersionAdobe PDF (281.46 kB)

View on publisher's site

View statistics

Full metadata record

Field	Value	Language
dc.contributor.author	Watanabe, S https://orcid.org/0000-0001-5211-3283	en_US
dc.contributor.author	Kuzhiumparambil, U https://orcid.org/0000-0003-0582-6779	en_US
dc.contributor.author	Fu, S https://orcid.org/0000-0002-6238-3612	en_US
dc.date.available	2018-02-22	en_US
dc.date.issued	2018-03-01	en_US
dc.identifier.citation	AAPS Journal, 2018, 20 (2)	en_US
dc.identifier.uri	http://hdl.handle.net/10453/131026
dc.description.abstract	© 2018, American Association of Pharmaceutical Scientists. The number of new psychoactive substances keeps on rising despite the controlling efforts by law enforcement. Although metabolism of the newly emerging drugs is continuously studied to keep up with the new additions, the exact structures of the metabolites are often not identified due to the insufficient sample quantities for techniques such as nuclear magnetic resonance (NMR) spectroscopy. The aim of the study was to characterise several metabolites of the synthetic cannabinoid (1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl) methanone (UR-144) by NMR spectroscopy after the incubation with the fungus Cunninghamella elegans. UR-144 was incubated with C. elegans for 72 h, and the resulting metabolites were chromatographically separated. Six fractions were collected and analysed by NMR spectroscopy. UR-144 was also incubated with human liver microsomes (HLM), and the liquid chromatography-high resolution mass spectrometry analysis was performed on the HLM metabolites with the characterised fungal metabolites as reference standards. Ten metabolites were characterised by NMR analysis including dihydroxy metabolites, carboxy and hydroxy metabolites, a hydroxy and ketone metabolite, and a carboxy and ketone metabolite. Of these metabolites, dihydroxy metabolite, carboxy and hydroxy metabolites, and a hydroxy and ketone metabolite were identified in HLM incubation. The results indicate that the fungus is capable of producing human-relevant metabolites including the exact isomers. The capacity of the fungus C. elegans to allow for NMR structural characterisation by enabling production of large amounts of metabolites makes it an ideal model to complement metabolism studies.	en_US
dc.relation.ispartof	AAPS Journal	en_US
dc.relation.isbasedon	10.1208/s12248-018-0209-6	en_US
dc.subject.classification	Pharmacology & Pharmacy	en_US
dc.subject.mesh	Microsomes, Liver	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Cunninghamella	en_US
dc.subject.mesh	Cannabinoids	en_US
dc.subject.mesh	Indoles	en_US
dc.subject.mesh	Chromatography, High Pressure Liquid	en_US
dc.subject.mesh	Magnetic Resonance Spectroscopy	en_US
dc.subject.mesh	Molecular Structure	en_US
dc.subject.mesh	Tandem Mass Spectrometry	en_US
dc.subject.mesh	Metabolomics	en_US
dc.title	Structural Elucidation of Metabolites of Synthetic Cannabinoid UR-144 by Cunninghamella elegans Using Nuclear Magnetic Resonance (NMR) Spectroscopy	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	20	en_US
utslib.for	1115 Pharmacology and Pharmaceutical Sciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Mathematical and Physical Sciences
pubs.organisational-group	/University of Technology Sydney/Strength - C3 - Climate Change Cluster
pubs.organisational-group	/University of Technology Sydney/Strength - CCET - Centre for Clean Energy Technology
pubs.organisational-group	/University of Technology Sydney/Strength - CFS - Centre for Forensic Science
pubs.organisational-group	/University of Technology Sydney/Students
utslib.copyright.status	open_access
pubs.issue	2	en_US
pubs.publication-status	Published	en_US
pubs.volume	20	en_US

Abstract:

© 2018, American Association of Pharmaceutical Scientists. The number of new psychoactive substances keeps on rising despite the controlling efforts by law enforcement. Although metabolism of the newly emerging drugs is continuously studied to keep up with the new additions, the exact structures of the metabolites are often not identified due to the insufficient sample quantities for techniques such as nuclear magnetic resonance (NMR) spectroscopy. The aim of the study was to characterise several metabolites of the synthetic cannabinoid (1-pentyl-1H-indol-3-yl) (2,2,3,3-tetramethylcyclopropyl) methanone (UR-144) by NMR spectroscopy after the incubation with the fungus Cunninghamella elegans. UR-144 was incubated with C. elegans for 72 h, and the resulting metabolites were chromatographically separated. Six fractions were collected and analysed by NMR spectroscopy. UR-144 was also incubated with human liver microsomes (HLM), and the liquid chromatography-high resolution mass spectrometry analysis was performed on the HLM metabolites with the characterised fungal metabolites as reference standards. Ten metabolites were characterised by NMR analysis including dihydroxy metabolites, carboxy and hydroxy metabolites, a hydroxy and ketone metabolite, and a carboxy and ketone metabolite. Of these metabolites, dihydroxy metabolite, carboxy and hydroxy metabolites, and a hydroxy and ketone metabolite were identified in HLM incubation. The results indicate that the fungus is capable of producing human-relevant metabolites including the exact isomers. The capacity of the fungus C. elegans to allow for NMR structural characterisation by enabling production of large amounts of metabolites makes it an ideal model to complement metabolism studies.

Please use this identifier to cite or link to this item:

http://hdl.handle.net/10453/131026