A simple reverse phase analytical technique was established for quantification of single and combinational drugs. A simple, economic, accurate reverse phase isocractic RP-HPLC method was established for the simultaneous quantification of Sofosbuvir, Velpatasvir and Voxilaprevir in bulk and tablet dosage forms. The estimation was done by using Discovery C18 (250×4.6mm,5µm) column with the flow rate of 1.0 ml/min, at λmax 260 nm. Solution-A was 0.1% OPA (pH 1.8) in water and solution -B was Acetonitrile (mobile phase: solution A: solution B, 50:50 v/v). The Rt for Sofosbuvir, Velpatasvir and Voxilaprevir is 2.458 min., 3.282 min and 4.003 min. respectively. The system was established and validated as per ICH guidelines.