title: In vitro metabolism of a novel synthetic cannabinoid, EAM-2201, in human liver microsomes and human recombinant cytochrome P450s.
abstract: In vitro metabolism of a new synthetic cannabinoid, EAM-2201, has been investigated with human liver microsomes and major cDNA-expressed cytochrome P450 (CYP) isozymes using liquid chromatography-high resolution mass spectrometry (LC-HRMS). Incubation of EAM-2201 with human liver microsomes in the presence of NADPH resulted in the formation of 37 metabolites, including nine hydroxy-EAM-2201 (M1-M9), five dihydroxy-EAM-2201 (M10-M14), dihydrodiol-EAM-2201 (M15), oxidative defluorinated EAM-2201 (M16), two hydroxy-M16 (M17 and M18), three dihydroxy-M16 (M19-M21), N-dealkyl-EAM-2201 (M22), two hydroxy-M22 (M23 and M24), dihydroxy-M22 (M25), EAM-2201 N-pentanoic acid (M26), hydroxy-M26 (M27), dehydro-EAM-2201 (M28), hydroxy-M28 (M29), seven dihydroxy-M28 (M30-M36), and oxidative defluorinated hydroxy-M28 (M37). Multiple CYPs, including CYP1A2, 2B6, 2C8, 2C9, 2C19, 2D6, 2J2, 3A4, and 3A5, were involved in the metabolism of EAM-2201. In conclusion, EAM-2201 is extensively metabolized by CYPs and its metabolites can be used as an indicator of EAM-2201 abuse.
authors.affiliation: College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Ju Hyun
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Forensic Chemistry Laboratory, Forensic Science Division, Supreme Prosecutor's Office, 157 Banpo-daero, Seocho-gu, Seoul 137-730, Republic of Korea.
authors.forename: Hee Seung
authors.initials: HS
authors.lastname: Kim
authors.affiliation: College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Tae Yeon
authors.initials: TY
authors.lastname: Kong
authors.affiliation: College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea.
authors.forename: Joo Young
authors.initials: JY
authors.lastname: Lee
authors.affiliation: Forensic Chemistry Laboratory, Forensic Science Division, Supreme Prosecutor's Office, 157 Banpo-daero, Seocho-gu, Seoul 137-730, Republic of Korea.
authors.forename: Jin Young
authors.initials: JY
authors.lastname: Kim
authors.affiliation: Forensic Chemistry Laboratory, Forensic Science Division, Supreme Prosecutor's Office, 157 Banpo-daero, Seocho-gu, Seoul 137-730, Republic of Korea.
authors.forename: Moon Kyo
authors.initials: MK
authors.lastname: In
authors.affiliation: College of Pharmacy, The Catholic University of Korea, 43 Jibong-ro, Wonmi-gu, Bucheon-si, Gyeonggi-do 420-743, Republic of Korea. Electronic address: sianalee@catholic.ac.kr.
authors.forename: Hye Suk
authors.initials: HS
authors.lastname: Lee
mesh_terms: D001711:Biotransformation; D002186:Cannabinoids / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D066298:In Vitro Techniques; D007211:Indoles / Q000737:chemistry / Q000378:metabolism*; D013058:Mass Spectrometry / Q000379:methods; D008862:Microsomes, Liver / Q000187:drug effects* / Q000378:metabolism; D015394:Molecular Structure; D009281:Naphthalenes / Q000737:chemistry / Q000378:metabolism*; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism
chemical_list: C000611379:(4-ethyl-1-naphthalenyl)(1-(5-fluoropentyl)-1H-indol-3-yl)methanone; D002186:Cannabinoids; D007211:Indoles; D009281:Naphthalenes; D011994:Recombinant Proteins; D003577:Cytochrome P-450 Enzyme System
keywords: Cytochrome P450; EAM-2201; Human liver microsomes; In vitro metabolism; LC–HRMS; Synthetic cannabinoid