An LC–MS method for the determination of Valproate semisodium in human plasma was developed and validated. Sample preparation involved the protein precipitation method. Chromatographic separation was performed on Sunfire C18 5µm (150 X 4.6) mm column with the mobile phase consisting of Acetonitrile: 10 mM ammonium acetate buffer ::80:20 v/v. The interface used with the API 3000 LC-MS/MS was a turbo ion spray in which negetive ions were measured in MRM mode. The method was validated over the concentration range of 1.012 µg/mL. to 120.399 µg/mL. and the Lower limit of quantitation (LLOQ) was 1.012 µg/mL. The intra- and inter-day precision of the method at four concentrations was 2.26-10.67% and 3.58-10.49% .Stability of compounds was established in a series of stability experiments. The method can be used for the simultaneous determination of Valproate semisodium in human plasma.