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Analysis of enantiomers of sibutramine and its metabolites in rat plasma by liquid chromatography–mass spectrometry using a chiral stationary-phase column

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 chromatograp...

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Published in:Journal of pharmaceutical and biomedical analysis 2009-09, Vol.50 (2), p.267-270
Main 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
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cited_by cdi_FETCH-LOGICAL-c481t-628d17a08ee6d228480407c16b356b5d97943716d44c7468037bd2928b0f499a3
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creator Bae, Kyoungjin
Noh, Kyeumhan
Jang, Kiyoung
Kim, Sohee
Yong, Chul Soon
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Lee, Manhyung
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description 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.
doi_str_mv 10.1016/j.jpba.2009.04.024
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identifier ISSN: 0731-7085
ispartof Journal of pharmaceutical and biomedical analysis, 2009-09, Vol.50 (2), p.267-270
issn 0731-7085
1873-264X
language eng
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source ScienceDirect Freedom Collection
subjects Analysis
Analytical, structural and metabolic biochemistry
Animals
Antidepressive Agents - blood
Biological and medical sciences
Chiral separation
Chromatography, Liquid - methods
Cyclobutanes - blood
Di-desmethylsibutramine
Fundamental and applied biological sciences. Psychology
General pharmacology
LC/MS/MS
Medical sciences
Mono-desmethylsibutramine
Pharmacology. Drug treatments
Rats
Rats, Sprague-Dawley
Sibutramine
Stereoisomerism
title Analysis of enantiomers of sibutramine and its metabolites in rat plasma by liquid chromatography–mass spectrometry using a chiral stationary-phase column
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