Application of mass spectrometry to the structural identification of the metabolites of the synthetic cannabinoid JWH-018 and the determination of them in human urine

Smoking mixtures containing cannabimimetic indoles may still be illegally sold in Russia. Although a method for their analysis is required for forensic toxicology authorities, the detection of synthetic cannabinoids is a complicated analytical task because of low anticipated concentrations in urine and the lack of in vivo data on their metabolism. Here, the urinary metabolites of 1-pentyl-3-(1-naphthoyl)indole (JWH-018) and a procedure for determining them in urine are reported. Using gas and high-performance liquid chromatography combined with tandem mass spectrometry, two main monohydroxylated metabolites were identified in urine. Based on differences in their electron ionization MS/MS spectra, it is supposed that one of them is formed by the hydroxylation of an indole ring and the other, by the hydroxylation of a pentyl side chain. The main metabolites are almost completely excreted as conjugates with glucuronic acid. The structure of minor metabolites was proposed. The parent compound was not detected in urine at a level of 50 pg/mL 12 h after administration.