QUALITY BY DESIGN ASSISTED RP-HPLC METHOD FOR ESTIMATION OF TERIFLUNOMIDE AND ITS PROCESS IMPURITIES IN DRUG SUBSTANCE

Abstract

Objective: In this research, a validated RP-HPLC method for analyzing teriflunomide drug substance and its associated process-related impurities was developed with the assistance of the Quality by Design (QbD) approach. Material and Method: The QbD methodology employs statistical design of experiments to establish a robust method within a defined "design space." This design space outlines the experimental parameters' range within which alterations will not significantly impact the results. Chromatographic separation was done on HPLC system connected to a PDA detector, and the column used was the C18 YmC-Triart with specifications of 125 cm x 4.0 mm x 5.0 μm. The optimized mobile phase consisted of 0.5% triethylamine buffer with pH 4.0 (± 0.05) and acetonitrile in a 65:35 v/v ratio, flow rate of 1.0 ml/min. Detection wavelength of 210 nm. Result and Discussion: The developed RP-HPLC method successfully achieved high resolution, specificity, linearity, precision, accuracy, and robustness in quantifying both teriflunomide and its impurities simultaneously. Using a design of experiments (DoE) approach, critical method parameters were systematically identified and optimized, ensuring accurate and precise determination of impurity levels across the drug substance lifecycle. This validated method provides a thorough approach to ensuring the quality and safety of teriflunomide drug substances by delivering reliable data on impurity profiles. By applying Quality by Design (QbD) principles, not only does the method enhance understanding of the analytical process, but it also supports ongoing improvement and lifecycle management of the procedure.