Stability-indicating HPLC-charged aerosol detector method for quantification of six related impurities in bempedoic acid: AQbD approach with greenness assessment

A stability-indicating reverse-phase high-performance liquid chromatography method with charged aerosol detection was developed and validated for the quantitative determination of bempedoic acid and six related impurities. Due to weak or absent UV chromophores in the analyte and its impurities, the Charged aerosol detector was selected for its near-universal detection capability, enabling consistent and sensitive quantification. Method development followed an Analytical Quality by Design approach using a design-of-experiments strategy to evaluate the effects of mobile-phase pH, flow rate, and column temperature on critical analytical attributes, ensuring method robustness. Chromatographic separation was achieved on an XBridge BEH C18 XP column (150 × 4.6 mm, 2.5 µm) using gradient elution with 10 mM ammonium formate buffer (pH 4.0) and acetonitrile at a flow rate of 1.00 mL/min and column temperature of 40 °C. The method was validated according to ICH guidelines. Forced degradation studies confirmed its stability-indicating capability by effectively separating degradation products from the analyte. Greenness assessment using established green analytical chemistry metrics demonstrated favorable environmental performance with reduced solvent consumption and waste generation. The developed method is suitable for routine quality control and stability testing of bempedoic acid drug substance.