Background: A novel rapid, accurate, and stability-indicating reversed-phase high performance liquid chromatographic (RP-HPLC) and first derivative spectrophotometric determination were explained for the assay of vortioxetine (VRT) in bulk and pharmaceutical formulations. For RP-HPLC method, optimal separation and determination of VRT were achieved with a Waters Symmetry C-18, (100 x 4.6 mm, 3.5 mu m) analytical column using a mobile phase consisting of methanol:0.05 M potassium dihydrogen phosphate (pH:3.0 +/- 0.05) (30:70, v/v) in isocratic mode with flow rate of 1.3 mL min(-1). Injection volume was 20 mu L. The maximum absorption wavelength of VRT is 225.0 nm; hence, 225.0 nm was studied as the detection wavelength and column at 50 degrees C temperature. The caffeine was used as the internal standard (IS). On the other hand, the first derivative spectrophotometric method for the analysis of vortioxetine was performed by measuring the amplitude at 251.7 and 272.6 nm.