An approach for quantitative estimation of Mefloquin Hcl in formulation in presence of its degradation products. The method has shown adequate separation for Mefloquin Hcl from their associated main related compound and their degradation products. Separation was achieved on a Waters Symmetry, C18, 250 mm ´ 4.6 mm, 5 m ,column at 25°C temperature by using a mobile phase consisting Buffer– Methanol ( 25:75 v/v ) [Buffer: sodium hydrogen sulphate monohydrate in 1000 ml of water] at a flow rate of 0.7 ml/min, and UV detection at 280 nm. In the present study, comprehensive stress testing of Mefloquin Hcl was carried out according to ICH guideline Q1A (R2). The specificity of the method was determined by assessing interference from the placebo and by stress testing of the drug (forced degradation). Drug was subjected to Acid hydrolysis, Alkali hydrolysis, Oxidation, Dry heat and Photolysis to apply stress conditions. There were no other coeluting, interfering peaks from excipients, impurities, or degradation products due to variable stress conditions, and the method is specific for determination of Mefloquin Hcl in the presence of degradation products. The method was validated in terms of linearity, precision, accuracy, specificity, robustness and solution stability. The linearity of the proposed method was investigated in the range of 50-150 μg/ml (r2 = 0.9995) for Mefloquin Hcl. Degradation products produced as a result of stress studies did not interfere in the estimation of Mefloquin Hcl and the assay can thus be considered stability-indicating.