Development and Validation of a Novel Stability-Indicating RP-HPLC Method for Simultaneous Determination of Tezacaftor and Ivacaftor in Fixed Dose Combination.

Abstract

A simple and precise novel stability-indicating method for the simultaneous estimation of tezacaftor and ivacaftor in combined tablet dosage form was developed and validated using reversed-phase high-performance liquid chromatography (RP-HPLC). The method is being reported for the first time and includes an estimation of degradation products produced post-stress conditions without any extraction or derivatization. The chromatographic separation of the drugs was achieved with a Symmetry Shield RP18 Column (100Å, 5μm, 4.6mm × 250mm) using a mixture of buffer, methanol and acetonitrile (42:27:31v/v/v) as mobile phase. The buffer used in mobile phase contained 35mM potassium dihydrogen phosphate, and its pH was adjusted to 7.0±0.02 with 20% orthophosphoric acid. The instrument was set at flow rate of 1.2 mL min-1 at ambient temperature and the wavelength of UV-visible detector at 275nm. The developed method could be suitable for the quantitative determination of these drugs in pharmaceutical preparations and also for quality control in bulk manufacturing. Stress testing was performed to prove the specificity. No interference was observed from its stress degradation products. The statistical analysis was done by using F-test and t-test at 95% confidence level.