A high throughput liquid chromatography-tandem mass spectrometric (LC-MS/MS) method for the determination and quantification of anti-cancer drug Paclitaxel in human plasma is described for the application to therapeutic drug monitoring. It is rapid and sensitive binary phase reversed phase LC-MS/MS method equipped with electro spray ionization (ESI) source and C18 column (100 mm x 4.6mm, 5μm), operating in the positive ion and multiple reaction monitoring (MRM) mode. The extraction of Paclitaxel and Carbamazepine (Internal standard) from the human plasma was carried out by two phase liquid-liquid extraction (LLE) method using methyl tert butyl ether (MTBE) as an extractive solvent giving extracts free from endogenous interferences. The retention time of Paclitaxel is 1.44 minutes with the flow rate of 0.5 mL/minutes. Sample preparation by this method yielded very good and consistent mean recoveries of Paclitaxel and IS. The method was linear over the dynamic range 5.00 to 3000.00 ng/mL (r2 0.997). The lower limit of detection and quantification for Paclitaxel on mass was found to be 5 ng/mL. This method was fully validated as per USFDA and EMEA guidelines. Conclusion: The proposed LCMS/MS method has better performance in terms of simplicity, sensitivity, stability and specificity than the previously reported methods. Moreover, there is rapid sample preparation, adequate retention and better extraction efficiency with less matrix interferences. Therefore, it can be considered as a suited bio-analytical tool for therapeutic drug monitoring and pharmacokinetic analysis during chemotherapy.