Detection and tentative identification of urinary phase I metabolites of phenylacetylindole cannabimimetics JWH-203 and JWH-251, by GC–MS and LC–MS/MS

The synthetic phenylacetylindole cannabimimetics, JWH-203 and JWH-251, have been identified in ‘herbal’ smoking mixtures following the widespread legislative control of ‘first generation’ compounds such as JWH-018 and CP47, 497(C8). N-Alkylindole cannabimimetics (including phenylacetylindoles) undergo extensive metabolism and little or none of the parent compounds are found in urine. Utilizing GC–MS and LC–MS/MS, a series of JWH-203 and JWH-251 urinary metabolites have been tentatively identified. These are products of mono- and dihydroxylation, monohydroxylation combined with formation of carbonyl group on the N-pentyl chain, carboxylation of N-pentyl chain and N-dealkylation combined with monohydroxylation. Additionally, trihydroxylated metabolites were detected for JWH-203. No parent compounds were detected. The monohydroxylated metabolites with the hydroxyl group positioned on the N-pentyl chain were the most abundant and were found to be suitable for establishing ingestion of JWH-203 or JWH-250. Maximum urinary concentrations of chain-monohydroxylated metabolites were observed at 2.5–3 h (JWH-203) and 6–10 h (JWH-251) following ingestion. These metabolites were observed (GC–MS) for to 10 and 8 days (JWH-203 and JWH-251, respectively).