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

by Selleckchem | May 05 2023

A 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 for drug quantification in the biological fluids, as well as in bulk and marketed dosage forms.

Comments：

This passage describes a study in which a high-performance liquid chromatography (HPLC) method was developed and optimized for the quantification of raloxifene hydrochloride using Quality by Design (QbD) principles. The study employed Taguchi design for factor screening and face-centered cubic design for method optimization, and identified buffer volume percentage and isocratic flow rate as critical method parameters that significantly influence tailing factor and theoretical plate number. The method operable design region (MODR) was identified and liquid chromatographic separation was 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. The developed analytical method was validated according to ICH guidelines, demonstrating high levels of linearity, precision, accuracy, robustness, and sensitivity. Monte Carlo simulations were used to attain the best plausible chromatographic resolution and corroborate the MODR. The developed HPLC method was also validated for the quantification of raloxifene hydrochloride in rat plasma samples, as well as in bulk and marketed dosage forms, and was found to be sensitive, rapid, reproducible, and economical. Forced degradation and stability studies also supported the aptness of the developed method for drug quantification in biological fluids.