DEVELOPMENT AND VALIDATION OF AN LC-MS-MS METHOD FOR CABOZANTINIB IN HUMAN PLASMA USING NAPROXEN AS AN INTERNAL STANDARD USING QUALITY BY DESIGN (QBD)

Abstract

The current studies describe the development and validation of an LC-MS-MS method for Cabozantinib in human plasma using naproxen as an internal standard using Quality by Design (QbD) (IS). For sample preparation, solid-phase extraction was used and linearity was observed for drug concentrations ranging from 5 to 1000 ng/mL The method was systemically optimized using the Box-Behnken design, with mobile phase flow rate (X1), pH (X2), and mobile phase composition (X3) as method variables and retention time (Rt) (Y1) and peak area (Y2) as responses. Optimization studies revealed a reduction in the variability associated with method variables which improved method robustness. Validation studies of the developed method revealed that Cabozantinib in human plasma has good linearity, accuracy, precision, selectivity, and sensitivity. Stability studies in human plasma using freeze-thaw, bench-top, short-term and long-term cycles and auto sampler stability revealed no change in the drug's percent recovery. In a nutshell, the developed method yielded satisfactory results for Cabozantinib analysis in human plasma.