Design and validation of a stability-indicating RP-HPLC technique for quantifying ivacaftor in bulk and commercial formulations

Aim of this study is to develop a novel Reverse Phase-High performance liquid chromatography (RP-HPLC) method was design and validated for accurately estimating ivacaftor (IVF) in granule form, including its degraded products, within stressful conditions without extraction or derivatization. The drugs were separated chromatographically with a Kromacil C18, 4 µm, (4.6 ×250 mm) and a mobile phase containing 50:50 methanol (MeOH) and acetonitrile (ACN). Photodiode array (PDA) detector was set to a wavelength of max plot 200 - 400 nm, and the instrument was set up at a flow rate of 1.0 mL/min. The developed method could be useful for accurately measuring IVF in pharmaceutical products, as well as quality control during large-scale production. Method showed high sensitivity and precision, with an IVF detection limit of (LOD) 0.00208 μg/mL and a quantification limit of (LOQ) 0.00631 μg/mL. The analysis was completed in under 5 min, with a retention time of 4.26 min. A force degradation study (FDS) was performed to confirm specificity, and there was no interference from stress-induced degradation products. It revealed that the highest degradation occurred in acidic conditions (0.1 N Hydrochloric acid at 80º C for 6 h) with a 21.88 % reduction, while the lowest degradation was observed under thermal conditions (80º C for 6 h) with 6.51 %. IVF has good thermal stability, with a 100.18 % assay confirming its accurate quantification in marketed formulations. The method is efficient and suitable for quality control laboratories.