title: Analysis of enantiomers of sibutramine and its metabolites in rat plasma by liquid chromatography-mass spectrometry using a chiral stationary-phase column.
abstract: Sibutramine, a monoamine reuptake inhibitor, is used as a racemate, for the treatment of obesity. It is converted in vivo mainly to two desmethyl active metabolites, mono-desmethylsibutramine (MDS) and di-desmethylsibutramine (DDS). In the present study, we introduced a rapid and simple chromatographic method for separating the R(+)- and S(-)-isomers of sibutramine, MDS, and DDS, respectively. The stereoisomers of the three compounds were extracted from rat plasma using diethyl ether and n-hexane under alkaline conditions. After evaporating the organic layer, the residue was reconstituted in the mobile phase (10 mM ammonium acetate buffer adjusted to pH 4.03 with acetic acid:acetonitrile, 94:6, v/v). The enantiomers in the extract were separated on a Chiral-AGP stationary-phase column and were quantified in a tandem mass spectrometry. The accuracy and precision of the assay were in accordance with FDA regulations for the validation of bioanalytical methods. This method was used to measure the concentrations of the enantiomers of sibutramine, MDS, and DDS in plasma after a single oral dose of 10 mg/kg racemic sibutramine in rats.
authors.affiliation: College of Pharmacy, Catholic University of Daegu, Hayang-eup, Kyoungbuk 712-702, South Korea.
authors.forename: Kyoungjin
authors.initials: K
authors.lastname: Bae
authors.forename: Kyeumhan
authors.initials: K
authors.lastname: Noh
authors.forename: Kiyoung
authors.initials: K
authors.lastname: Jang
authors.forename: Sohee
authors.initials: S
authors.lastname: Kim
authors.forename: Chul Soon
authors.initials: CS
authors.lastname: Yong
authors.forename: Han-Gon
authors.initials: HG
authors.lastname: Choi
authors.forename: Jong Seong
authors.initials: JS
authors.lastname: Kang
authors.forename: Jianbo
authors.initials: J
authors.lastname: Chen
authors.forename: Eunsook
authors.initials: E
authors.lastname: Ma
authors.forename: Manhyung
authors.initials: M
authors.lastname: Lee
authors.forename: Beom Soo
authors.initials: BS
authors.lastname: Shin
authors.forename: Kwang-Il
authors.initials: KI
authors.lastname: Kwon
authors.forename: Wonku
authors.initials: W
authors.lastname: Kang
mesh_terms: D000818:Animals; D000928:Antidepressive Agents / Q000097:blood*; D002853:Chromatography, Liquid / Q000379:methods*; D003503:Cyclobutanes / Q000097:blood*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013237:Stereoisomerism
chemical_list: D000928:Antidepressive Agents; D003503:Cyclobutanes; C058254:sibutramine