Quality by design‐steered development and validation of analytical and bioanalytical methods for raloxifene: Application of Monte Carlo simulations and variance inflation factor

Abstract

A sensitive, rapid, reproducible, and economical HPLC method is reported for the quantification of raloxifene hydrochloride employing Quality by Design (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, that is, 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 ggmobile phase at 0.9 mL min À1 flow rate, λ max of 280 nm, and column temperature of 40 C. Validation of the developed analytical method was accomplished as per International Council on Harmonization (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 demarcated MODR. 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.

QbD-Driven Development and Validation of a Bioanalytical LC–MS Method for Quantification of Paliperidone in Human Plasma

“…QbD-driven methodologies focus on understanding critical method variables and their influence on critical analytical attributes, ultimately contributing to the development of reliable and high-performing analytical techniques. This approach aligns with the ever-increasing demand for precise and sensitive bioanalytical methods that can be employed in pharmacokinetic, bioequivalence, and toxicological studies (Pant et al, 2023).…”

Impact of Forensic Marketing on Consumer Behavior: Evidence From Beauty Products\’ Purchase Decision

“…Discriminant validity is supported as the diagonal values of each latent variable range from 0.878 to 0.946, suggesting that each variable is distinct and measures different aspects of the overall construct as it is close to 1 as the threshold(Kenny, 1976;Schmitt & Stults, 1986). VIF values range from 3.072 to 2.949(Pant et al, 2023), below the threshold of 10, indicating no severe multicollinearity among latent variables. The statistical results for hypothesis 1 demonstrate high internal consistency, robust composite reliability, and satisfactory convergent validity, supporting the use of these variables as reliable and valid measures in the research study.…”