AQbD-guided statistical optimization and multi-metric greenness evaluation of liquid chromatographic method for analysis of bempedoic acid in pharmaceutical dosage forms

A new chromatography-based analytical technique was developed for the quantification of bempedoic acid in drug product. In this study, an Analytical Quality by Design (AQbD) strategy was employed. A 3 2 full factorial experimental design was used to determine the effect of two mobile phase components: acetonitrile–water composition and flow rate, on three chromatographic performance metrics; retention time, number of theoretical plates, and peak asymmetry. This was done by employing a C18 reversed-phase column under isocratic conditions utilizing a mobile phase consisting of 30% ACN : 70% water (pH 2.5) and delivered at a flow rate of 0.8 mL min − 1 . UV detection was performed at 276 nm. With these optimized conditions, the analyte (bempedoic acid) was resolved from all excipients in the drug product, and eluted at approximately 3.42 min with a narrow, symmetric peak. Linearity was observed throughout the concentration range of 5–25 µg mL⁻¹ (R² = 0.9993). Precision was adequate (% RSD < 1.5%); and accuracy was confirmed via recoveries that ranged from 101.21 to 101.52%. The limit of detection (LOD) and limit of quantitation (LOQ) were determined to be 0.81 µg mL⁻¹ and 2.07 µg mL⁻¹, respectively. Additionally, forced degradation studies of BMP under oxidative, acidic, and alkaline conditions demonstrated the ability of the method to distinguish BMP from its respective degradation products. An eco-sustainability assessment indicated moderate environmental performance, with an Eco-Scale score of 82 and an AGREEprep score of 0.38. The developed method demonstrates moderate greenness while maintaining high analytical performance.