Volume 7, Issue 2, 1 February 2015, Pages 131-142
Moscow Antidoping Centre, Elizavetinsky per. 10, Moscow, Russian Federation
Abstract
The data are reported
for an in vitro metabolism study of two novel synthetic cannabinoids,
N-(1-adamantyl)-1-pentyl-1H-indole-3-carboxamide (APICA) and its
fluorinated analog
N-(1-adamantyl)-1-(5-fluoropentyl)-1H-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 N-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 in vivo confirmation of the formed in vitro
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
N-despentyl (desfluoropentyl) hydroxyadamantyl metabolite also provides
good retrospectivity to confirm the administration of any of these
cannabinoids. © 2014 John Wiley & Sons, Ltd.
Author keywords
5F-APICA; Anti-doping analysis; APICA; STS-135; Synthetic cannabinoids
Indexed keywords
EMTREE drug terms: cannabinoid derivative; n (1
adamantyl) 1 (5 fluoropentyl) 1h indole 3 carboxamide; n (1 adamantyl) 1
pentyl 1h indole 3 carboxamide; unclassified drug; adamantane;
cannabinoid; indole derivative;
N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide; street drug
EMTREE medical terms: Article; defluorination; drug
isolation; drug metabolism; drug use; electrospray mass spectrometry;
human; human cell; in vitro study; liquid chromatography; liver
microsome; metabolite; phase 1 clinical trial; priority journal;
quadrupole mass spectrometry; urinalysis; analogs and derivatives;
chemistry; halogenation; mass fragmentography; metabolism; tandem mass
spectrometry; urine
MeSH: Adamantane; Cannabinoids; Chromatography, Liquid;
Gas Chromatography-Mass Spectrometry; Halogenation; Humans; Indoles;
Microsomes, Liver; Street Drugs; Tandem Mass Spectrometry
Medline is the source for the MeSH terms of this document.
Medline is the source for the MeSH terms of this document.
Chemicals and CAS Registry Numbers: adamantane, 281-23-2;Adamantane; Cannabinoids; Indoles; N-(adamtan-1-yl)-1-pentyl-1H-indole-3-carboxamide; Street Drugs
