Implementing the Quality by Design (QbD) Framework for the Simultaneous Estimation of Letrozole and Palbociclib Using the UV-Spectrophotometric Technique

A straightforward, economic and rapid UV-visible analytical method was developed and validated using the Quality by Design (QbD) approach for the simultaneous estimation of Letrozole and Palbociclib in bulk and synthetic drug mixtures. Letrozole and Palbociclib exhibited maximum absorbance at 240 nm and 220 nm, respectively, when Methanol: 0.2% Ortho Phosphoric acid (50:50% v/v) was used as the solution. The method was optimized using the Design of Experiment (DoE) approach, which helped identify and optimize the impact of critical variables through statistical multivariate analysis and modeling to facilitate continuous improvement. The optimized method was validated according to ICH Q2(R1) guidelines, demonstrating excellent linearity within a concentration range of 2-10 µg/mL, with correlation coefficients (R²) of 0.999 for Letrozole and 0.9996 for Palbociclib. The limits of detection (LOD) for Letrozole and Palbociclib were 0.384 µg/mL and 0.225 µg/mL, respectively, while the limits of quantification (LOQ) were 1.165 µg/mL and 0.684 µg/mL, respectively. The accuracy recovery rates ranged from 98.91-99.56% for Letrozole and 99.86-101.12% for Palbociclib. This QbD-based method offers a systematic and proactive approach to ensuring the quality, reliability, and efficiency of both analytical and manufacturing processes, benefiting the pharmaceutical industry and other sectors.