Implementing Quality by Design approach in Analytical Reverse Phase High Performance Liquid Chromatography Method Development and Validation for the Determination of Fedratinib

Abstract

A novel, accurate, precise, specific, sensitive, and robust reverse phase high performance liquid chromatography (RP-HPLC) method was developed and validated for the determination of Fedratinib using the analytical quality by design (AQbD) approach mentioned in International Council for Harmonisation (ICH) Q8 (R2) guidelines. By implementing QbD in HPLC methods, ruggedness and robustness will be verified early in the stage of method development to ensure the method's performance over the product's lifetime. Design Expert® (12.0.12.0) modeling software (Stat-Ease Inc., Minneapolis, MN, USA) was used for response surface methodology (RSM). Plackett-Burman design was employed for the factor screening studies to identify the critical method parameters (CMP) affecting the critical quality attributes (CQA). The selected CMP's were systematically optimized using Central-composite design (CCD). Statistical analysis of the responses was done by applying analysis of variance. Chromatographic separation was accomplished on Agilent C18 (150×4.6 mm, 5 µm) column and PDA-UV detection was set at 268 nm. The optimized and predicted data from Design Expert software consisted of mobile phase Acetonitrile: 0.1% OPA buffer pH 4.18 (43: 57% v/v), pumped at a flow rate of 0.967 mL/min gave the highest desirability of 1. The developed chromatographic method was validated as per ICH Q2 (R1) guidelines and found to be linear over a concentration range of 15–90 µg/mL with a correlation coefficient of 0.999. Degradation studies were performed by exposing the drug to various stress conditions as per ICH Q1A (R2) guidelines, and significant degradation was found in acidic conditions.