QbD Driven Approach for Method Development and Validation for The Determination of Gilteritinib By RP-HPLC

Quality by Design (QbD) assisted approach was used for development of robust and rugged RP-HPLC method and validated as per ICH guidelines. Methods developed using QbD approach are highly robust, cost effective, uses good experimental designs, have shorter run times, optimization can be done by statistical analysis and can be easily validated compared with the traditional methods developed by one-factor-at-a-time (OFAT) approach. Central-composite design (CCD) under Response Surface Methodology (RSM) was used for development of optimized method based on desirability functions approach. The factors selected for the present study were % organic composition in mobile phase, column temperature, flow rate and responses investigated were retention time of the drug and theoretical plate count. Chromatographic separation was achieved using Phenomenex C18 (150 mm x 4.6 mm, 5) column. Statistical analysis of CCD experimental data was done by applying ANOVA and the selected mathematical models for the responses were found to be significant with p < 0.05. The optimized conditions based on highest desirability value of 1 was achieved using Acetonitrile: Phosphate buffer (42.1: 57.9% v/v) mobile phase pumped at 0.93ml/min flow rate at 31.70C. The drug eluted at a retention time of 2.655 min. Finally the developed method was validated according to ICH Q2 (R1) guidelines. All the system suitability parameters were found to be within the limits. Forced degradation studies were performed according to ICH guidelines with notable degradation found in acidic condition.