Study on the phase I metabolism of novel synthetic cannabinoids, APICA and its fluorinated analogue. Issue 2 (26th November 2014)

• Record Type: Journal Article
• Authors: Sobolevsky, Tim; Prasolov, Ilya; Rodchenkov, Grigory
• Is Part Of: Drug testing and analysis. Volume 7:Issue 2(2015:Feb.)
• Page Start: 131
• Page End: 142
• Publication Date: 2014-11-26
• Subjects: Drugs -- Analysis -- Periodicals; Drug testing -- Periodicals; Chemistry, Forensic -- Periodicals; 615.1901
• DOI: 10.1002/dta.1756
• Languages: English
• ISSNs: 1942-7603

Abstract

<abstract abstract-type="main"> <title> <x xml:space="preserve">Abstract</x> </title> <p>The data are reported for an <italic>in vitro</italic> metabolism study of two novel synthetic cannabinoids, <italic>N</italic>‐(1‐adamantyl)‐1‐pentyl‐1<italic>H</italic>‐indole‐3‐carboxamide (APICA) and its fluorinated analog <italic>N</italic>‐(1‐adamantyl)‐1‐(5‐fluoropentyl)‐1<italic>H</italic>‐indole‐3‐carboxamide (5F‐APICA, STS‐135), which are active ingredients of smoking mixtures sold in Russia since 2012. The cannabinoids were isolated from herbal mixtures using preparative liquid chromatography and then incubated with human liver microsomes (HLMs). The formed metabolites were characterized by liquid chromatography – triple quadrupole mass spectrometry and high‐resolution mass spectrometry with electrospray ionization in positive ion mode. It was found that HLMs produce mono‐, di‐, and trihydroxylated metabolites, as well as <italic>N</italic>‐desalkyl metabolites, which can be further hydroxylated; the amide bond resisted the metabolic cleavage. For 5F‐APICA, a series of oxidative defluorination products formed as well. For <italic>in vivo</italic> confirmation of the formed <italic>in vitro</italic> metabolites, spot urine samples from drug users were analyzed with the created method. It was shown that for the detection of APICA abuse, the preferred metabolites are the di‐ and tri‐hydroxylated species, while in case of 5F‐APICA, a monohydroxy metabolite is a better target. The <italic>N</italic>‐despentyl (desfluoropentyl) hydroxyadamantyl metabolite also provides good retrospectivity to confirm the administration of any of these cannabinoids. Copyright © 2014 John Wiley & Sons, Ltd.</p> </abstract>