Stability Indicating RP-HPLC Method for the Determination of Dronedarone Hydrochloride and Its Potential Process-Related Impurities in Bulk Drug and Pharmaceutical Dosage Form

Abstract

Simple, sensitive and accurate stability indicating analytical method for dronedarone has been developed and validated using RP-HPLC technique. Developed method is used to evaluate the assay and related substances of dronedarone drug substance and tablets (Multaq ? ). The drug substance was subjected to the stress conditions such as hydrolysis (acid and base), oxidation, photolysis and thermal degradation as per International Conference on Harmonization (ICH) pre - scribed stress conditions to show the stability-indicating the nature of the method. Significant degradation was observed during acid and base hydrolysis, and peroxide degradation. The major degredants were identified by LC-MS, FTIR and 1 H NMR spectral analysis. The chromatographic conditions were optimized using an impurity-spiked solution and the samples generated from forced degradation studies. In the developed HPLC method, the resolution between dronedar - one, process-related impurities, (namely Imp-1, Imp-2, Imp-3, Imp-4, Imp-5, Imp-6, Imp-7, Imp-8, Imp-9, Imp-10 and Imp-11) and degradation products were found to be greater than 1.5. The eleven potential process related impurities were separated on an Ascentis ? Express C18 column (4.6 × 10 cm i.d., particle size 2.7 μm) at a flow rate of 1.2 mL . min - 1 . The LC method employed a linear gradient elution and the detection wavelength at 220 nm. The chroma - tographic behavior of all the impurities was examined under variable compositions of different solvents, temperatures and pH values.