title: Determination of major metabolites of MAM-2201 and JWH-122 in in vitro and in vivo studies to distinguish their intake.
abstract: 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.
authors.affiliation: National Forensic Service, 331-1 Sinwol-7-dong, Yangcheon-gu, Seoul 158-707, Republic of Korea.
authors.forename: Moonhee
authors.initials: M
authors.lastname: Jang
authors.affiliation: National Forensic Service, 331-1 Sinwol-7-dong, Yangcheon-gu, Seoul 158-707, Republic of Korea.
authors.forename: Ilchung
authors.initials: I
authors.lastname: Shin
authors.affiliation: National Forensic Service, 331-1 Sinwol-7-dong, Yangcheon-gu, Seoul 158-707, Republic of Korea. Electronic address: yangwk@korea.kr.
authors.forename: Wonkyung
authors.initials: W
authors.lastname: Yang
authors.affiliation: National Forensic Service, 331-1 Sinwol-7-dong, Yangcheon-gu, Seoul 158-707, Republic of Korea.
authors.forename: Hyejin
authors.initials: H
authors.lastname: Chang
authors.affiliation: Institute of Pharmaceutical Science and Technology and College of Pharmacy, Hanyang University, Ansan, Gyeonggi-do 426-791, Republic of Korea.
authors.forename: Hye Hyun
authors.initials: HH
authors.lastname: Yoo
authors.affiliation: National Forensic Service, 331-1 Sinwol-7-dong, Yangcheon-gu, Seoul 158-707, Republic of Korea.
authors.forename: Jaesin
authors.initials: J
authors.lastname: Lee
authors.affiliation: National Forensic Service, 331-1 Sinwol-7-dong, Yangcheon-gu, Seoul 158-707, Republic of Korea.
authors.forename: Eunmi
authors.initials: E
authors.lastname: Kim
mesh_terms: D006801:Humans; D006900:Hydroxylation; D013287:Illicit Drugs / Q000032:analysis* / Q000737:chemistry; D066298:In Vitro Techniques; D007211:Indoles / Q000032:analysis* / Q000737:chemistry; D008862:Microsomes, Liver / Q000737:chemistry*; D015394:Molecular Structure; D009281:Naphthalenes / Q000032:analysis* / Q000737:chemistry
chemical_list: C000594853:1-(5-fluoropentyl)-3-(4-methyl-1-naphthoyl)indole; D013287:Illicit Drugs; D007211:Indoles; D009281:Naphthalenes; C587938:(4-methyl-1-naphthyl)-(1-pentylindol-3-yl)methanone
keywords: In vitro metabolism; JWH-122; MAM-2201; Synthetic cannabinoid; Urine