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
2016 (English)In: Journal of Chromatography A, ISSN 0021-9673, E-ISSN 1873-3778, Vol. 1451, 97-106 p.Article in journal (Refereed) PublishedText
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.
AM-2201, Synthetic cannabinoid, Metabolites, Plasma, Liquid chromatography-tandem mass spectrometry
IdentifiersURN: urn:nbn:se:liu:diva-130125DOI: 10.1016/j.chroma.2016.05.020ISI: 000377725900012PubMedID: 27208987OAI: oai:DiVA.org:liu-130125DiVA: diva2:948593
Funding Agencies|Intramural Research Program of the National Institute on Drug Abuse (NIDA), National Institutes of Health (NIH)2016-07-122016-07-112016-07-18Bibliographically approved