A sensitive and stability indicating liquid chromatography - tandem mass spectrophotometry method is developed for the simultaneous detection and quantification of 3-(1-piperazinyl)-1,2-benzisothiazole and 4-chloro-1,2-benzisothiazole potential treated as possible genotoxic impurities of lurasidone. The method utilizes Hypersil BDS C18 column (50 mm � 4.6 mm, 3.0 m) with electrospray ionization in multiple reaction monitoring mode for quantitation of two potential genotoxic impurities. The method is validated following the International Conference on Harmonization guidelines and is proficient to quantitate 3-(1-piperazinyl)-1,2-benzisothiazole at 0.3 ppm and 4-chloro-1,2- benzisothiazole at 0.3 ppm with respect to 5.0 mg/mL of lurasidone. The proposed method is specific, accurate and precise. The method is linear in the range of 0.3 ppm -4.5 ppm in respect to 3-(1-piperazinyl)-1,2-benzisothiazole and 4-chloro-1,2-benzisothiazole. The correlation coefficients are 0.9996 and 0.9998 in each case which matches the range of limit of quantification-150 of predictable permitted level (3.0 ppm). The impurities are not present in the studied three pure and formulation batches of lurasidone. The accuracy of the method is ranged between 98.53 and 102.93 for both potential genotoxic impurities. This method can be further utilized as an excellent quality control tool for low level quantization of both 3-(1-piperazinyl)-1,2-benzisothiazole and 4-chloro-1,2-benzisothiazole as potential low level genotoxic impurities of lurasidone. © 2019 University of Chemical Technology and Metallurgy.