title: Identification of non-reported bupropion metabolites in human plasma.
abstract: Bupropion and its three active metabolites exhibit clinical efficacy in the treatment of major depression, seasonal depression and smoking cessation. The pharmacokinetics of bupropion in humans is highly variable. It is not known if there are any non-reported metabolites formed in humans in addition to the three known active metabolites. This paper reports newly identified and non-reported metabolites of bupropion in human plasma samples. Human subjects were dosed with a single oral dose of 75 mg of an immediate release bupropion HCl tablet. Plasma samples were collected and analysed by LC-MS/MS at 0, 6 and 24 h. Two non-reported metabolites (M1 and M3) were identified with mass-to-charge (m/z) ratios of 276 (M1, hydration of bupropion) and 258 (M3, hydroxylation of threo/erythrohydrobupropion) from human plasma in addition to the known hydroxybupropion, threo/erythrohydrobupropion and the glucuronidation products of the major metabolites (M2 and M4-M7). These new metabolites may provide new insight and broaden the understanding of bupropion's variability in clinical pharmacokinetics. © 2016 The Authors Biopharmaceutics & Drug Disposition Published by John Wiley & Sons Ltd.
authors.affiliation: Department of Pharmaceutical Sciences University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Jamie N
authors.initials: JN
authors.lastname: Connarn
authors.affiliation: Department of Pharmaceutical Sciences University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Ruijuan
authors.initials: R
authors.lastname: Luo
authors.affiliation: Department of Chemistry, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Jim
authors.initials: J
authors.lastname: Windak
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
authors.forename: Xinyuan
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Division of Quantitative Methods and Modeling, Office of Research and Standards, Office of Generic Drugs, Center for Drug Evaluation and Research, US Food and Drug Administration, Silver Spring, Maryland, 20993, USA.
authors.forename: Andrew
authors.initials: A
authors.lastname: Babiskin
authors.affiliation: Department of Psychiatry, University of Michigan Medical School, Ann Arbor, 48109, USA.
authors.forename: Marisa
authors.initials: M
authors.lastname: Kelly
authors.affiliation: Department of Psychiatry, University of Michigan Medical School, Ann Arbor, 48109, USA.
authors.forename: Gloria
authors.initials: G
authors.lastname: Harrington
authors.affiliation: Department of Clinical Pharmacy, University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Vicki L
authors.initials: VL
authors.lastname: Ellingrod
authors.affiliation: Department of Psychiatry, University of Michigan Medical School, Ann Arbor, 48109, USA.
authors.forename: Masoud
authors.initials: M
authors.lastname: Kamali
authors.affiliation: Department of Psychiatry, University of Michigan Medical School, Ann Arbor, 48109, USA.
authors.forename: Melvin
authors.initials: M
authors.lastname: McInnis
authors.affiliation: Department of Pharmaceutical Sciences University of Michigan, Ann Arbor, MI, 48109, USA.
authors.forename: Duxin
authors.initials: D
authors.lastname: Sun
mesh_terms: D018687:Antidepressive Agents, Second-Generation / Q000097:blood* / Q000494:pharmacology; D016642:Bupropion / Q000031:analogs & derivatives* / Q000097:blood* / Q000494:pharmacology; D002853:Chromatography, Liquid / Q000379:methods; D006801:Humans; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*
chemical_list: D018687:Antidepressive Agents, Second-Generation; C496216:hydrobupropion; C580748:hydroxybupropion; D016642:Bupropion
keywords: LC-MS/MS; bupropion; metabolite identification