The detection of the urinary metabolites of 1‐[(5‐fluoropentyl)‐1H‐indol‐3‐yl]‐(2‐iodophenyl)methanone (AM‐694), a high affinity cannabimimetic, by gas chromatography – mass spectrometry

Abstract

AM-694 (1-[(5-fluoropentyl)-1H-indol-3-yl]-(2-iodophenyl)methanone), a synthetic indole-based cannabimimetic, was first reported to the European Monitoring Centre for Drugs and Drug Addiction (EMCDDA) via the Early Warning System (EWS) by Irish authorities in 2010. Using gas chromatography-mass spectrometry (GC-MS), we have identified six AM-694 metabolites in post-ingestion samples. The metabolites were tentatively identified as products of (1) hydrolytic defluorination, (2) carboxylation, (3) monohydroxylation of N-alkyl chain, and (4) hydrolytic defluorination combined with monohydroxylation of N-alkyl chain. The parent compound was not detected. The excretion of major metabolites was observed up to 117 h following administration. One metabolite (a product of hydrolytic defluorination) was also identified in urine samples from two individuals admitted to hospital suffering from suspected drug overdoses.

In vivo detection of the new psychoactive substance AM-694 and its metabolites

“…In this paper we describe for the first time in Italy the report of an intoxication where the SC AM-694 (see Figure 1) and its main metabolites, the hydrolytically defluorinated metabolite, M1 and the carboxylated metabolite, M2, [25] (see Figure 2) were identified in biological fluids (urine) by LC-MS/MS. AM-694 or 1-(5-fluoropentyl)-3-(2-iodobenzoyl)indole is an aminoalkylindole.…”

Pharmacology and toxicology of the synthetic cannabinoid receptor agonists

“…A volunteer study investigating the metabolites of AB-001 found that they were detectable for up to 160 hours following oral administration [35], while metabolites of AM-694 were detected up to 117 hours post oral ingestion [23]. Analysis of thirty-four urine samples collected from patients admitted with suspected drug intoxication revealed metabolites of JWH-203 (n = 28), JWH-251 (n = 8), JWH-250 (11 of the JWH-203 samples) and JWH-018 (1 of the JWH-203 samples) [36].…”

“…Whilst the pharmacokinetics of these substances remains largely unknown, there are some data available from a combination of clinical cases, studies and self-experiments [1,16,[21][22][23] (Gardin 2009). Because of the wide chemical diversity of the SCRAs it is not possible to extrapolate pharmacological properties between, and potentially within, different SCRA classes.…”

“…Grigoryev et al investigated AB-001, an aminoalkylindole [23]. Four subjects ingested this drug, at doses of either 13 or 26 mg. Urine was tested for metabolites of AB-001 at various times up to one week after drug administration.…”

Screening for new psychoactive substances in hair by ultrahigh performance liquid chromatography–electrospray ionization tandem mass spectrometry

“…Furthermore, in hair (and in keratinized matrices in general) parent, un-metabolized drugs accumulate prevalently, in comparison with the corresponding metabolites [13]. Conversely, studies performed both in vivo and in vitro on some of the synthetic cannabinoids showed that they are extensively metabolized, and in many cases no parent compound is detectable in urine [14][15][16][17][18]. Thus, whereas the determination of synthetic cannabinoids in urine and blood will therefore be faced with the issue of identifying several metabolites often not well known, hair analysis can be focussed directly on the parent drug.…”