Determination of major metabolites of MAM-2201 and JWH-122 in in vitro and in vivo studies to distinguish their intake

Abuse of fluorinated synthetic cannabinoid analogs to avoid existing legal regulations has increased globally. The fluorinated JWH-122 analog, MAM-2201, was first reported in September 2012 as an ingredient in herbal mixtures in Korea. MAM-2201 is more potent than JWH-122 and a fatal intoxication case has been reported. In this study, we identified major MAM-2201 and JWH-122 metabolites from in vitro metabolism studies using human liver microsomes and compared the results with those of urine specimens from suspected MAM-2201 or JWH-122 users. MAM-2201 and JWH-122 produced common metabolites, N-5-hydroxylated, N-4-hydroxylated and carboxylated JWH-122 metabolites. Trace amounts of an N-4-hydroxylated MAM-2201 metabolite, a characteristic MAM-2201 metabolite, was detected in only a few urine specimens from MAM-2201 users. Both in vitro and in vivo studies demonstrated that N-5-hydroxylated JWH-122 metabolite was the primary metabolite of MAM-2201, whereas N-4-hydroxylated JWH-122 metabolite was predominant in JWH-122 metabolism. Based on these results, relative concentrations of N-5- and N-4-hydroxylated JWH-122 metabolites should be considered to verify MAM-2201 or JWH-122 users.