Establishment of a stability indicating HPLC method for dronedarone hydrochloride in tablets and in cyclodextrin inclusion complexes: application to degradation kinetic studies

The stability indicating HPLC method for the determination of dronedarone (DRO) hydrochloride in tablets and in inclusion complexes with cyclodextrin was carried out on a C18 column using a buffer solution (0.3% glacial acetic acid; pH 4.9) and acetonitrile (35:65, v/v) as mobile phase. The method validation according to ICH guidelines demonstrated acceptable results. Dronedarone was exposed to stress conditions, and drug-degradation kinetics was studied. Additionally, the degraded samples were analyzed by mass spectrometry and the preliminary toxicity against 3T3 cells was also determined. The results obtained evidenced that dronedarone degradation kinetics in alkaline conditions followed first-order reaction and that inclusion complexation with cyclodextrin reduced its chemical degradation. Among the samples exposed to stress conditions, only the photodegraded samples presented cytotoxic effects. Moreover, assay results were compared to a previously validated micellar electrokinetic chromatography method, showing non-significant difference (p > 0.05). The combination of HPLC, mass spectrometry and cytotoxicity study could be an important tool for the screening of DRO pharmaceutical forms, improving quality and safety in the development of novel drug delivery systems.