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Quantification of [1-(5-fluoropentyl)-1H-indol-3-yl](naphthalene-1-yl)methanone (AM-2201) and 13 metabolites in human and rat plasma by liquid chromatography-tandem mass spectrometry
Clinical Pharmacology & Therapeutics Research Branch, Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD, USA.
Clinical Pharmacology & Therapeutics Research Branch, Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD, USA.
Clinical Pharmacology & Therapeutics Research Branch, Chemistry and Drug Metabolism Section, Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD, USA.
Designer Drug Research Unit, Intramural Research Program, National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH), Baltimore, MD, USA.
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2016 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1451, 97-106 p.Article in journal (Refereed) PublishedText
Abstract [en]

AM-2201 is a popular synthetic cannabinoid first synthesized in 2000. AM-2201 pharmacokinetic and pharmacodynamic data are scarce, requiring further investigation. We developed a sensitive method for quantifying AM-2201 and 13 metabolites in plasma to provide a tool to further metabolic, pharmacolcinetic and pharmacodynamic studies. Analysis was performed by liquid chromatography-tandem mass spectrometry. Chromatographic separation was performed by gradient elution on a biphenyl column with 0.1% formic acid in water/0.1% formic acid in acetonitrile:methanol 50:50 (v/v) mobile phase. Sample preparation (75 mu L) consisted of an enzymatic hydrolysis and a supported liquid extraction. The method was validated with human plasma with a 0.025 or 0.050-50 mu g/L, working range, and cross validated for rat plasma. Analytical recovery was 88.8-110.1% of target concentration, and intra- (n = 30) and inter-day (n = 30) imprecision amp;lt;11.9% coefficient of variation. Method recoveries and matrix effects ranged from 58.4-84.4% and -62.1 to -15.6%, respectively. AM-2201 and metabolites were stable (+/- 20%) at room temperature for 24 h, at 4 degrees C for 72 h, and after three freeze-thaw cycles, and for 72 h in the autosampler after extraction. The method was developed for pharmacodynamic and pharmacokinetic studies with controlled administration in rats but is applicable for pre-clinical and clinical research and forensic investigations. Rat plasma specimen analysis following subcutaneous AM-2201 administration demonstrated the suitability of the method. AM-2201, JWH-018 N-(5-hydroxypentyl), and JWH-018 N-pentanoic acid concentrations were 4.8 +/- 1.0, 0.15 +/- 0.03, and 0.34 +/- 0.07 mu g/L, respectively, 8h after AM-2201 administration at 0.3 mg/kg (n = 5). Published by Elsevier B.V.

Place, publisher, year, edition, pages
Elsevier, 2016. Vol. 1451, 97-106 p.
Keyword [en]
AM-2201, Synthetic cannabinoid, Metabolites, Plasma, Liquid chromatography-tandem mass spectrometry
National Category
Analytical Chemistry
Identifiers
URN: urn:nbn:se:liu:diva-130125DOI: 10.1016/j.chroma.2016.05.020ISI: 000377725900012PubMedID: 27208987OAI: oai:DiVA.org:liu-130125DiVA: diva2:948593
Note

Funding Agencies|Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)

Available from: 2016-07-12 Created: 2016-07-11 Last updated: 2016-07-18Bibliographically approved

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Wohlfarth, Ariane
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