Development and Validation of an Analytical Quality by Design‐Based Robust Liquid Chromatography Method for Determination of Eight Process and Degradation Impurities in Corticosteroid Drug Product

ABSTRACT The current study focuses on the development and validation of a robust liquid chromatographic method for detecting process‐related and degradation impurities in prednisone tablet formulations, a drug commonly used to treat inflammatory and respiratory disorders. The chromatographic separation was achieved using an X‐Select HSS T3 column (250 mm × 4.6 mm, 5 µm) with a gradient elution system comprising potassium phosphate buffer (pH 2.0) and a mixture of acetonitrile, water, and tetrahydrofuran (50:35:15, v/v/v), delivered at a flow rate of 1.0 mL/min. Detection was done at 244 nm. The method was verified using ICH Q2(R2) guidelines and showed excellent linearity from the limit of quantification to 200% of the specification level ( R 2 > 0.9991). Recovery values ranged from 95.3% to 103.4%, confirming accuracy. Precision was within acceptable levels (relative standard deviation <5.0%). Forced degradation experiments demonstrated the method's stability‐indicating ability, with considerable degradation observed under alkaline, oxidative, photolytic, and thermal stress conditions. Importantly, mass balance was continuously reached between 98% and 102%, demonstrating the dependability of the hypothesized degrading mechanisms. A systematic quality by design approach was used to assess crucial technique parameters and ensure their robustness under purposeful modifications.