In vitro metabolism of synthetic cannabinoid AM1220 by human liver microsomes and Cunninghamella elegans using liquid chromatography coupled with high resolution mass spectrometry

Watanabe, S; Kuzhiumparambil, U; Fu, S

In vitro metabolism of synthetic cannabinoid AM1220 by human liver microsomes and Cunninghamella elegans using liquid chromatography coupled with high resolution mass spectrometry

Watanabe, S

Kuzhiumparambil, U

Fu, S

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Publication Type:: Journal Article
Citation:: Forensic Toxicology, 2018, 36 (2), pp. 435 - 446
Issue Date:: 2018-07-01

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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	2018-04-21	en_US
dc.date.issued	2018-07-01	en_US
dc.identifier.citation	Forensic Toxicology, 2018, 36 (2), pp. 435 - 446	en_US
dc.identifier.issn	1860-8965	en_US
dc.identifier.uri	http://hdl.handle.net/10453/131784
dc.description.abstract	© 2018, The Author(s). Purpose: Identifying intake of synthetic cannabinoids generally requires the metabolism data of the drugs so that appropriate metabolite markers can be targeted in urine testing. However, the continuous appearance of new cannabinoids during the last decade has made it difficult to keep up with all the compounds including {1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}(naphthalen-1-yl)methanone (AM1220). In this study, metabolism of AM1220 was investigated with human liver microsomes and the fungus Cunninghamella elegans. Methods: Metabolic stability of AM1220 was analysed by liquid chromatography–tandem mass spectrometry in multiple reaction monitoring mode after 1 µM incubation in human liver microsomes for 30 min. Tentative structure elucidation of metabolites was performed on both human liver microsome and fungal incubation samples using liquid chromatography–high-resolution mass spectrometry. Results: Half-life of AM1220 was estimated to be 3.7 min, indicating a high clearance drug. Nine metabolites were detected after incubating human liver microsomes while seven were found after incubating Cunninghamella elegans, leading to 11 metabolites in total (five metabolites were common to both systems). Demethylation, dihydrodiol formation, combination of the two, hydroxylation and dihydroxylation were the observed biotransformations. Conclusions: Three most abundant metabolites in both human liver microsomes and Cunninghamella elegans were desmethyl, dihydrodiol and hydroxy metabolites, despite different isomers of dihydrodiol and hydroxy metabolites in each model. These abundant metabolites can potentially be useful markers in urinalysis for AM1220 intake.	en_US
dc.relation.ispartof	Forensic Toxicology	en_US
dc.relation.isbasedon	10.1007/s11419-018-0424-y	en_US
dc.subject.classification	Analytical Chemistry	en_US
dc.title	In vitro metabolism of synthetic cannabinoid AM1220 by human liver microsomes and Cunninghamella elegans using liquid chromatography coupled with high resolution mass spectrometry	en_US
dc.type	Journal Article
utslib.citation.volume	2	en_US
utslib.citation.volume	36	en_US
utslib.for	039902 Forensic Chemistry	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	36	en_US

Abstract:

© 2018, The Author(s). Purpose: Identifying intake of synthetic cannabinoids generally requires the metabolism data of the drugs so that appropriate metabolite markers can be targeted in urine testing. However, the continuous appearance of new cannabinoids during the last decade has made it difficult to keep up with all the compounds including {1-[(1-methylpiperidin-2-yl)methyl]-1H-indol-3-yl}(naphthalen-1-yl)methanone (AM1220). In this study, metabolism of AM1220 was investigated with human liver microsomes and the fungus Cunninghamella elegans. Methods: Metabolic stability of AM1220 was analysed by liquid chromatography–tandem mass spectrometry in multiple reaction monitoring mode after 1 µM incubation in human liver microsomes for 30 min. Tentative structure elucidation of metabolites was performed on both human liver microsome and fungal incubation samples using liquid chromatography–high-resolution mass spectrometry. Results: Half-life of AM1220 was estimated to be 3.7 min, indicating a high clearance drug. Nine metabolites were detected after incubating human liver microsomes while seven were found after incubating Cunninghamella elegans, leading to 11 metabolites in total (five metabolites were common to both systems). Demethylation, dihydrodiol formation, combination of the two, hydroxylation and dihydroxylation were the observed biotransformations. Conclusions: Three most abundant metabolites in both human liver microsomes and Cunninghamella elegans were desmethyl, dihydrodiol and hydroxy metabolites, despite different isomers of dihydrodiol and hydroxy metabolites in each model. These abundant metabolites can potentially be useful markers in urinalysis for AM1220 intake.

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http://hdl.handle.net/10453/131784