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Background: Free valproic acid is shows no characteristic absorption in the ultraviolet region (above 235 nm), therefore its direct quantification and also the quantification of the corresponding metabolites from human plasma has proven to be challenging. Aim: The aim of our study was to develop and validate an effective LC-MS method for the determination of valproic acid in human plasma without using solid phase extraction as sample preparation, with a short analysis time and high sensitivity. Materials and methods: Valproic acid was analyzed on a reversed-phase column (Zorbax SB-C18, 100 mm x 3 mm ID, 3.5 μm) under isocratic conditions using a mobile phase of a 40: 60 (v/v) mixture of acetonitrile and 0.1%(v/v) acetic acid in water. The flow rate was 1 mL/min and the column temperature 45 C. In these chromatographic conditions, the retention time was 2.3 minute for valproic acid. The detection of the …