A simple, precised, accurate method was developed for the estimation of Samidorphan and Olanzapine in human plasma using the Dolutegravir as internal standard by RP-HPLC (Reverse phase-High performance Liquid Chromatographic) technique. Chromatographic conditions used are stationary phase Inertsil 250 4.6mm, 5mm, Mobile phase 0.01N Ammonium acetate Buffer   : Acetonitrile 60:40 and flow rate was maintained at 1.0ml/min, detection wave length was 228 nm, column temperature was set to 30^oC and diluent was mobile phase Conditions were finalized as optimized method. Retention time of Samidorphan and Olanzapine were found to be 2.909 min and 3.408min. %CV of theSamidorphan and Olanzapine was found  to be 0.42%  and 0.52%. %Recovery was obtained as 99.96% and  101.47% . The linearity concentration is in the range of 2.750-275.000 for Samidorphan and 4.750-475.000 for Olanzapine and linearity is (r2 = 0.999) . Further, the reported method was validated as per the ICH guidelines and found to be well within the acceptable range. The proposed method is simple, rapid, accurate, precise, and appropriate for pharmacokinetic and therapeutic drug monitoring in the clinical laboratories.

Key words:Samidorphan, Olanzapine, RP-HPLC