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The paper describes HPLC, UV spectrophotometric and non aqueous titrimetric method for the estimation of poorly water soluble protease inhibitor. Ritonavir in raw material and tablet dosage form. HPLC analysis was carried out in a C18 column using acetonitrile, methanol, and buffer in the ratio 60: 20: 20 (v/v/v) at 240 nm. For the spectrophotometric determination, methanolic solution of Ritonavir was reacted with 3-methyl benzothiazolin-2-one hydrazone (MBTH). The oxidative coupled green coloured chromogen was analysed at 633 nm. Non aqueous titration was carried out using perchloric acid as titrant and the end point was determined using crystal violet as indicator. The three methods were validated and statistically evaluated to correlate the difference between the methods for estimation of Ritonavir in pharmaceutical dosage form.