Analysis of enantiomers of sibutramine and its metabolites in rat plasma by liquid chromatography-mass spectrometry using a chiral stationary-phase column
- Authors
- Bae, Kyoungjin; Noh, Kyeumhan; Jang, Kiyoung; Kim, Sohee; Yong, Chul Soon; Choi, Han-Gon; Kang, Jong Seong; Chen, Jianbo; Ma, Eunsook; Lee, Manhyung; Shin, Beom Soo; Kwon, Kwang-il; Kang, Wonku
- Issue Date
- Sep-2009
- Publisher
- ELSEVIER SCIENCE BV
- Keywords
- Sibutramine; Mono-desmethylsibutramine; Di-desmethylsibutramine; Chiral separation; LC/MS/MS
- Citation
- JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS, v.50, no.2, pp.267 - 270
- Indexed
- SCIE
SCOPUS
- Journal Title
- JOURNAL OF PHARMACEUTICAL AND BIOMEDICAL ANALYSIS
- Volume
- 50
- Number
- 2
- Start Page
- 267
- End Page
- 270
- URI
- https://scholarworks.bwise.kr/erica/handle/2021.sw.erica/40904
- DOI
- 10.1016/j.jpba.2009.04.024
- ISSN
- 0731-7085
- 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. (C) 2009 Elsevier B.V. All rights reserved.
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