A novel and stability indicating, experimental design assisted liquid chromatographic method developed for the estimation of related substances of bromfenac sodium sesquihydrate. Stability indication of method established by forced degradation study. The chromatographic separation was attained with Kromosil C18,125 x 4.0mm, 5μm using gradient elution using mobile phase-A consists of a mixture of pH 4.8 ammonium acetate buffer and the mobile phase-B consists a mixture of methanol: Acetonitrile (500:500 v/v), respectively. Column temperature maintained at 30◌֯ C with wavelength detection at 265nm.The develop method is validated as per International Conference on Harmonization (ICH) norms. Central composite experimental design (CCD) was employed to check the robustness of the method.