Quality by Design (QbD)-Steered Development and Validation of Analytical and Bioanalytical Methods for Raloxifene: Application of Monte Carlo Simulations and Variance Inflation Factor

Biomed Chromatogr. 2023 Apr 11:e5641. doi: 10.1002/bmc.5641. Online ahead of print.ABSTRACTA sensitive, rapid, reproducible and economical high-performance liquid chromatographic (HPLC) method is reported for the quantification of raloxifene hydrochloride employing QbD principles. Factor screening studies, employing Taguchi design, indicated buffer volume percentage and isocratic flow rate as the critical method parameters (CMPs), which significantly influence the chosen critical analytical attributes, i.e., tailing factor and theoretical plate number. Method conditions were subsequently optimized using face-centered cubic design with magnitude of variance inflation factor for assessing multicollinearity among CMPs. Method operable design region (MODR) was earmarked and liquid chromatographic separation optimized using 0.05 M citrate buffer, acetonitrile, and methanol (57:40:3 v/v/v) as mobile phase at 0.9 mL.min-1 flow rate, λmax of 280 nm and column temperature of 40°C. Validation of developed analytical method was accomplished as per ICH guidelines confirming high levels of linearity, precision, accuracy, robustness, and sensitivity. Application of Monte Carlo simulations enabled the attainment of best plausible chromatographic resolution and corroboration of the MODR, thus demarcated. Establishment and validation of the bioanalytical method using rat plasma samples, along with forced degradation and stability studies, corroborated the aptness of developed HPLC methods f...
Source: Biomedical Chromatography : BMC - Category: Biomedical Science Authors: Source Type: research