title: Identification of Metabolite Biomarkers of the Designer Hallucinogen 25I-NBOMe in Mouse Hepatic Microsomal Preparations and Human Urine Samples Associated with Clinical Intoxication.
abstract: 'NBOMe' (dimethoxyphenyl-N-[(2-methoxyphenyl)methyl]ethanamine) derivatives are a new class of designer hallucinogenic drugs widely available on the Internet. Currently, 2-(4-iodo-2,5-dimethoxyphenyl)-N-[(2-methoxyphenyl)methyl]ethanamine (25I-NBOMe) is the most popular abused derivative in the USA. There are little published data on the absorption, metabolism and elimination of 25I-NBOMe, or any of the other NBOMe derivatives. Therefore, there are no definitive metabolite biomarkers. We present the identification of fifteen 25I-NBOMe metabolites in phase I and II mouse hepatic microsomal preparations, and analysis of two human urine samples from 25I-NBOMe-intoxicated patients to test the utility of these metabolites as biomarkers of 25I-NBOMe use. The synthesis of two major urinary metabolites, 2-iodo-4-methoxy-5-[2-[(2-methoxyphenyl) methylamino]ethyl]phenol (2-O-desmethyl-5-I-NBOMe, M5) and 5-iodo-4-methoxy-2-[2-[(2-methoxyphenyl)methylamino]ethyl]phenol (5-O-desmethyl-2-I-NBOMe), is also presented. Seven phase II glucuronidated metabolites of the O-desmethyl or the hydroxylated phase I metabolites were identified. One human urine sample contained 25I-NBOMe as well as all 15 metabolites identified in mouse hepatic microsomal preparations. Another human urine sample contained no parent 25I-NBOMe, but was found to contain three O-desmethyl metabolites. We recommend β-glucuronidase enzymatic hydrolysis of urine prior to 25I-NBOMe screening and the use of M5 as the primary biomarker in drug testing.
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, PO Box 980613, Richmond, VA 23298-0613, USA jlpoklis@vcu.edu.
authors.forename: Justin L
authors.initials: JL
authors.lastname: Poklis
authors.affiliation: Department of Forensic Science, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Sara K
authors.initials: SK
authors.lastname: Dempsey
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Kai
authors.initials: K
authors.lastname: Liu
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, PO Box 980613, Richmond, VA 23298-0613, USA.
authors.forename: Joseph K
authors.initials: JK
authors.lastname: Ritter
authors.affiliation: Department of Forensic Science, Virginia Commonwealth University, Richmond, VA, USA Departments of Pathology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Carl
authors.initials: C
authors.lastname: Wolf
authors.affiliation: Department of Medicinal Chemistry, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Shijun
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Pharmacology and Toxicology, Virginia Commonwealth University, PO Box 980613, Richmond, VA 23298-0613, USA Department of Forensic Science, Virginia Commonwealth University, Richmond, VA, USA Departments of Pathology, Virginia Commonwealth University, Richmond, VA, USA.
authors.forename: Alphonse
authors.initials: A
authors.lastname: Poklis
mesh_terms: D000328:Adult; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D015198:Designer Drugs / Q000378:metabolism*; D004118:Dimethoxyphenylethylamine / Q000031:analogs & derivatives* / Q000378:metabolism / Q000506:poisoning / Q000652:urine; D006213:Hallucinogens; D006801:Humans; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008862:Microsomes, Liver / Q000378:metabolism*
chemical_list: D015415:Biomarkers; D015198:Designer Drugs; D004118:Dimethoxyphenylethylamine; D006213:Hallucinogens; C554181:2-(4-iodo-2,5-dimethoxyphenyl)-N-(2-methoxybenzyl)ethanamine