Detection of urinary metabolites of AM-2201 and UR-144, two novel synthetic cannabinoids

Drug Test Anal. 2012 Oct;4(10):745-53. doi: 10.1002/dta.1418. Epub 2012 Oct 5.

Abstract

Synthetic cannabinoids are the psychotropic compounds frequently identified as active components of smoking mixtures easily available via the Internet in several countries. These herbal blends have become extremely popular as a legal alternative to cannabis-based products and are difficult to detect by regular drug tests. Here we report on an in vitro and in vivo metabolism of AM-2201, 1-[(5-fluoropentyl)-1H-indol-3-yl]-(naphthalen-1-yl)methanone, and UR-144 (KM-X1), (1-pentylindol-3-yl)-(2,2,3,3-tetramethylcyclopropyl)methanone isolated using preparative liquid chromatography from the smoking mixtures sold in Russia. After incubation with human liver microsomes (HLM) as well as with cytochrome isoenzymes 3A4 and 2B6, the metabolic pathways were identified by means of liquid chromatography - triple quadrupole and high resolution mass spectrometry with electrospray ionization in positive mode. It was found that the in vitro reactions include mono- and dihydroxylation, loss of N-alkyl side chain and formation of dihydrodiol metabolites in case of AM-2201. The HLM were found to be superior over the other two isoenzymes for generation of cannabinoid metabolites. Finally, forensic urine samples were analyzed to validate the in vitro data and it has been shown that for both cannabimimetics the recommended screening targets are the monohydroxylated metabolites.

Keywords: AM-2201; KM-X1; UR-144; anti-doping analysis; synthetic cannabinoids.

MeSH terms

  • Cannabinoids / analysis
  • Cannabinoids / metabolism
  • Cannabinoids / urine*
  • Chromatography, High Pressure Liquid
  • Gas Chromatography-Mass Spectrometry
  • Humans
  • Illicit Drugs / chemistry
  • Illicit Drugs / metabolism
  • Illicit Drugs / urine*
  • Indoles / analysis
  • Indoles / metabolism
  • Indoles / urine*
  • Microsomes, Liver / metabolism
  • Naphthalenes / analysis
  • Naphthalenes / metabolism
  • Naphthalenes / urine*
  • Substance Abuse Detection
  • Tandem Mass Spectrometry

Substances

  • (1-pentyl-1H-indol-3-yl)(2,2,3,3-tetramethylcyclopropyl)methanone
  • 1-(5-fluoropentyl)-3-(1-naphthoyl)indole
  • Cannabinoids
  • Illicit Drugs
  • Indoles
  • Naphthalenes