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 1H 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.