STRATEGIC QBD IMPLEMENTATION IN RPHPLC-PDA METHOD FOR SIMULTANEOUS QUANTIFICATION OF CYSTIC FIBROSIS DRUGS TEZACAFTOR AND IVACAFTOR

Objective: A novel RP-HPLC PDA method was developed using a Quality by Design (QbD) approach for the simultaneous quantification of Tezacaftor and Ivacaftor medications employed in the management of cystic fibrosis. Material and Method: Optimization was performed by Central Composite Design by selecting mobile phase ratio of methanol, pH of buffer and flow rate as factors and evaluating responses namely retention time and tailing factor. This technique makes use of an Inertial ODS C18 column (250 x 4.6 mm, 5 μm particle size) in conjunction with a Waters module fitted with a photo diode array detector. The chromatographic conditions including a flow rate of 1.0 ml/min, a mobile phase composed of methanol and buffer in a 45:55 ratio, and a detection wavelength of 210 nm, were thoughtfully designed to effectively separate Tezacaftor and Ivacaftor. Result and Discussion: The method demonstrated remarkable accuracy, with average recoveries of 99.69% for ivacaftor and 100.06% for tezacaftor. The % assay results for system suitability, method precision, and intermediate precision consistently fell within the range of 99.91% to 100.37%. Linearity data exhibited correlation coefficient values of one for both Tezacaftor and Ivacaftor. The LOD and LOQ values for Tezacaftor and Ivacaftor were determined to be 0.56, 0.57, 1.69, and 1.74, respectively. The results obtained from the validation parameters demonstrate that this RP-HPLC method, developed using the QbD approach, is robust and dependable. It serves as a valuable tool for routine analysis and plays a pivotal role in bioanalytical and bioequivalence research within the realm of cystic fibrosis treatment. This method ensures precise and accurate quantification of Tezacaftor and Ivacaftor in combination tablet formulations.