STABILITY-INDICATING RP-HPLC METHOD FOR THE SIMULTANEOUS QUANTITATION OF OLMESARTAN MEDOXOMIL AND AMLODIPINE BESYLATE IN A COMBINED SYNTHETIC MIXTURE

Background: Fixed-dose combination tablets containing an angiotensin II receptor blocker and a calcium channel blocker have achieved widespread acceptance for the management of essential hypertension. Despite extensive clinical utilization, a single stability-indicating assay capable of resolving both actives from their degradation products in a combined synthetic matrix is not adequately documented. Objective: The present study was aimed at developing and validating a novel, stability-indicating reversed-phase high-performance liquid chromatographic (RP-HPLC) method for the simultaneous quantitation of Olmesartan Medoxomil (OLM) and Amlodipine Besylate (AMB) in a combined synthetic mixture. Methods: Chromatographic separation was achieved on a Phenomenex Luna C18 column (250 × 4.6 mm, 5 µm) using a gradient mobile phase consisting of 0.02 M potassium dihydrogen phosphate (pH 3.2 ± 0.05, orthophosphoric acid) and acetonitrile, at a flow rate of 1.0 mL/min and column temperature of 30°C. Photodiode array detection was employed in the range 200–400 nm, with quantitation extracted at 257 nm (OLM) and 237 nm (AMB). The method was validated in accordance with ICH Q2(R1) guidelines. Forced degradation studies were conducted under hydrolytic (acidic, alkaline), oxidative, thermal, photolytic, and humidity stress conditions per ICH Q1A(R2). Results: Base-line separation was attained within 18 min with resolution (Rs) > 5.0 between both analytes and their degradation products. Calibration curves were linear over the ranges of 20–150 and 5–37.5 µg/mL for OLM and AMB, respectively (r2 > 0.999). Accuracy (% recovery) ranged between 98.7% and 101.0%, while intra- and inter-day precisions showed RSD < 1.5%. Peak purity indices derived from PDA data (purity angle < purity threshold) confirmed the homogeneity of each analyte peak under all stress conditions. Significant degradation was observed under alkaline and oxidative stress, while the drugs remained relatively stable under thermal and photolytic exposure. Conclusion: The proposed RP-HPLC method is specific, accurate, precise, and stability indicating. It is suitable for routine quality control, stability testing, and dissolution profiling of dual-combination antihypertensive formulations.