Integrated Analytical Quality by Design and In Silico Modeling for Stability‐Indicating Ultra‐High‐Performance Liquid Chromatography Method Development and Validation for Impurity Profiling of Gilteritinib Fumarate
Method development study demonstrates robust separation of four impurities in gilteritinib fumarate, highlighting an efficient framework for pharmaceutical quality control.
Key Points
To develop and validate a stability-indicating ultra-high-performance liquid chromatography method for the simultaneous quantification of four specified process-related impurities in gilteritinib fumarate.
Integrated in silico retention modeling with a three-factor, three-level Box–Behnken experimental design to evaluate critical method parameters and establish an operable design region.
Conducted method validation according to International Council for Harmonisation guidelines, alongside forced degradation testing to evaluate stability-indicating capability.
Applied Monte Carlo simulations to verify operational robustness and assessed method sustainability using greenness analytical metrics.
Achieved baseline separation of all analytes within 20 minutes, yielding a critical-pair resolution exceeding 2.7 and tailing factors below 1.35.
Demonstrated linearity, precision, and accuracy with recoveries of 98.5%–101.3%, detection limits of approximately 0.08 µg mL⁻¹ for all impurities, and forced degradation mass balances of 97.39%–99.94%.