Sensitive and reproducible liquid chromatography-tandem mass spectrometry method for quantification of sibutramine in human plasma

Abstract

A sensitive and reproducible high-performance liquid chromatography-tandem mass spectrometry (MS-MS) method was developed and validated for the quantification of sibutramine in human plasma. Following liquid-liquid extraction, the analytes were separated using an isocratic mobile phase on a reverse-phase column and analyzed by MS-MS in the multiple reaction monitoring mode using the respective [M + H]+/product ions, m/z 280/125 for sibutramine and m/z 325/262 for citalopram as internal standard. The assay exhibited a linear dynamic range of 30–6000 pg/ml for sibutramine in human plasma. The lower limit of quantification was 30 pg/ml with a relative standard deviation of less than 4%. Acceptable precision and accuracy were obtained for concentrations over the standard curve range. A run time of 3.2 min for each sample made it possible to analyze more than 250 human plasma samples per day. The validated method was successfully used to analyze sibutramine in human plasma samples for application in a pharmacokinetic study.