Obesity can be considered as a chronic illness of epidemic proportion and its incidents have increased exponentially in recent years. The use of anti-obesity drugs such as sibutramine is somewhat helpful. There is a need to quantify such drugs in biological samples, which is generally quite difficult. In this report, we developed and validated a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for the quantification of sibutramine (SB) and its two metabolites N-des methyl sibutramine (DSB) and N-di desmethyl sibutramine (DDSB) in human plasma. Zorbax SBC18 (4.6 mm 75 mm, 3.5 mm, 80 A) analytical column and 5 mM ammonium formate:acetonitrile (10:90, v/v) mobile phase were used for chromatographic separation of SB, DSB and DDSB. Multiple reaction monitoring (MRM) in the positive mode was used to detect SB, DSB and DDSB at m/z 280.3/124.9, 266.3/ 125.3 and 252.2/124.9, respectively. Liquid-liquid extraction was used for the extraction of analytes and internal standard from human plasma. This method was validated over a linear concentration range of 10.0-10,000.0 pg/mL for SB, DSB and DDSB with correlation coefficients (r) of Z0.9997. The drug and the two metabolites were stable in plasma samples. The validated method was successfully applied in a bioequivalence and pharmacokinetic study with human volunteers under fasting condition. The use of anti-obesity drugs such as sibutramine ispoints helpful helpful. There is a need to quantify such drugs in biological samples, which is generally quite difficult. In this report, we developed and validated a simple, sensitive and specific liquid chromatography-tandem mass spectrometry (LC-MS / MS) method for the quantification of sibutramine (SB) and its two metabolites N-des methyl sibutramine ) and N-di desmethyl sibutramine (DDSB) in human plasma. Zorbax SBC18 (4.6 mm 75 mm, 3.5 mm, 80 A) analytical column and 5 mM ammonium formate: acetonitrile for chromatographic separation of SB, DSB and DDSB. Multiple reaction monitoring (MRM) in the positive mode was used to detect SB, DSB and DDSB at m / z 280.3 / 124.9, 266.3 / 125.3 and 252.2 / 124.9, respectively. extraction was used for the extraction of anal ytes and internal standard from human plasma. This method was validated over a linear concentration range of 10.0-10,000.0 pg / mL for SB, DSB and DDSB with correlation coefficients (r) of Z0.9997. The drug and the two metabolites were stable in plasma samples. The validated method was successfully applied in a bioequivalence and pharmacokinetic study with human volunteers under fasting conditions.