ABSTRACT:
A simple, precise, and reliable reverse-phase high-performance liquid chromatography (RP-HPLC) method was successfully developed and optimized for the simultaneous estimation of Olanzapine and Samidorphan in bulk and pharmaceutical dosage forms. Chromatographic separation was achieved using a Platisil C18 column with a mobile phase of methanol and KH₂PO₄ buffer (70:30 v/v, pH 3.5) at a flow rate of 1.0 ml/min, with detection at 225 nm. The method provided well-resolved peaks with good resolution, acceptable symmetry, and satisfactory system suitability parameters. Validation studies performed according to ICH guidelines confirmed linearity over the concentration ranges of 20–100 µg/ml for Olanzapine and 10–50 µg/ml for Samidorphan, with correlation coefficients of 0.9998 and 0.9997, respectively. Precision studies showed %RSD values below 2, accuracy studies demonstrated recoveries within 98–102%, and sensitivity was established through low LOD and LOQ values. Robustness studies indicated that minor variations in chromatographic conditions did not significantly affect performance. Forced degradation studies under acidic, basic, oxidative, thermal, and photolytic conditions revealed degradation of both drugs, but the method effectively separated degradation products from the main peaks, confirming its stability-indicating capability. Overall, the validated RP-HPLC method is robust, reproducible, and suitable for routine quality control, assay determination, and stability studies of Olanzapine and Samidorphan in pharmaceutical formulations.