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A novel, selective, sensitive and simple spectrophotometric method was developed and validated for the determination of the antidepressant duloxetine hydrochloride in pharmaceutical preparation. The method was based on the reaction of duloxetine hydrochloride with 1,2-naphthoquinone-4-sulphonate (NQS) in alkaline media to yield orange colored product. The formation of this complex was also confirmed by UV-visible, FTIR, ¹H NMR, Mass spectra techniques and thermal analysis. This method was validated for various parameters according to ICH guidelines. Beer’s law is obeyed in a range of 5.0–60 μg/mL at the maximum absorption wavelength of 480 nm. The detection limit is 0.99 μg/mL and the recovery rate is in a range of 98.10–99.57%. The proposed methods was validated and applied to the determination of duloxetine hydrochloride in pharmaceutical preparation. The results were statistically …