title: Determination of the active metabolite of sibutramine by liquid chromatography-electrospray ionization tandem mass spectrometry.
abstract: A sensitive and specific method for the determination of the active primary amine metabolite of sibutramine, N-di-desmethylsibutramine (BTS 54,505), in human plasma was developed, based on high-performance liquid chromatography (HPLC)-electrospray ionization tandem mass spectrometry (MS-MS). The samples were extracted from plasma with methyl tert.-butyl ether, followed by separation and evaporation after addition of the internal standard, propranolol, and basification with sodium hydroxide. The residue was reconstituted in mobile phase and injected into the HPLC-MS-MS system. Chromatography was performed on an ODS MS column with a mobile phase consisting of acetonitrile (containing 0.1% trifluoroacetic acid, v/v)-0.1% trifluoroacetic acid (55:45, v/v) at a flow-rate of 0.3 ml/min. Multiple reaction monitoring using precursor-->product ion combinations at m/z 252.00-->125.00 and 260.00-->115.70 was applied to determine BTS 54,505 and propranolol, respectively. Linearity was confirmed in the concentration range 0.328-32.8 ng/ml in human plasma and the imprecision of this assay was less than 19.90% over the entire concentration range. The method is sufficiently sensitive and repeatable to be used in pharmacokinetic studies.
authors.affiliation: Department of Pharmaceutics, School of Pharmacy, Fudan University, Shanghai 200032, PR China.
authors.forename: Jun
authors.initials: J
authors.lastname: Chen
authors.forename: Wei
authors.initials: W
authors.lastname: Lu
authors.forename: Qizhi
authors.initials: Q
authors.lastname: Zhang
authors.forename: Xinguo
authors.initials: X
authors.lastname: Jiang
mesh_terms: D001067:Appetite Depressants / Q000032:analysis* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001711:Biotransformation; D002138:Calibration; D002851:Chromatography, High Pressure Liquid; D003503:Cyclobutanes / Q000032:analysis* / Q000493:pharmacokinetics*; D006801:Humans; D007202:Indicators and Reagents; D012015:Reference Standards; D015203:Reproducibility of Results; D012996:Solutions; D021241:Spectrometry, Mass, Electrospray Ionization
chemical_list: D001067:Appetite Depressants; D003503:Cyclobutanes; D007202:Indicators and Reagents; D012996:Solutions; C058254:sibutramine