Stability-indicating HPLC analysis of Azilsartan Medoxomil potassium: A QbD-based method development and validation

Developing robust analytical methods for Azilsartan Medoxomil Potassium (AZM), a potent angiotensin II receptor antagonist, is essential due to its instability and limited aqueous solubility. This study aimed to establish and optimize a high-performance liquid chromatography (HPLC) method for the accurate and stability-indicating quantification of AZM and its impurities in the active pharmaceutical ingredient (API) and formulated drug products. Using an Analytical Quality by Design (A-QbD) framework, method parameters were optimized through a Central Composite Design (CCD), focusing on variables such as acetonitrile concentration, buffer pH, and flow rate to achieve desirable tailing factors and retention times. The validated method demonstrated high accuracy, precision, and sensitivity, with a linear response range of 10-50 μg/mL and limits of detection and quantification as low as 0.00607 and 0.01841 ng/mL, respectively. Forced degradation studies confirmed the method's selectivity and stability-indicating capabilities by identifying distinct degradation products under various stress conditions, including acidic, basic, oxidative, and photolytic environments. The validated HPLC method was successfully applied to a commercial AZM formulation, yielding assay values within acceptable limits for quality control. This study provides a reliable and robust analytical method that ensures the quality and stability of AZM throughout its lifecycle.