Described is a simple, rapid, selective, and stability-indicating RP-LC method for the determination of process and degradation-related impurities of bosentan monohydrate. Chromatographic separation was achieved on Zorbax SB-Phenyl column thermostated at 35°C under gradient elution by a binary mixture of solvent A (60% phosphate buffer, pH 2.5, and 40% methanol) and solvent B (acetonitrile) at a flow rate of 1.0 mL/min. Forced degradation was carried out under acidic, alkaline, oxidative, photolytic, and thermal conditions. Significant degradation is observed in acid and alkali stress conditions. Process- and degradation-related impurities were characterized by mass spectrometry, 1H NMR, and FT-IR spectral data. Validation of the developed method was carried out as per ICH requirements. Regression analysis shows an “r” value (correlation coefficient) of greater than 0.999 for bosentan and five potential impurities. This method was capable to detect the five impurities at 0.01% of the test concentration of 1.0 mg mL-1.