The aim of the present work was to develop and validate an accurate, stability indicating RP-HPLC method for the determination of abrisentan and its process impurities in bulk and dosage forms. The drug was subjected to different stress conditions, significant degradation was observed during acid hydrolysis and peroxide degradation. The chromatographic conditions were optimized using an impurity-spiked solution and forced degradation samples. The method was developed using Agilent XDB-C18 (150×4.5 mm, 5µ) column and 10 mM NH4OAc (pH 5.2 adjusted with acetic acid): ACN as the mobile phase with 1 ml/min flow rate and effluents were monitored at 289 nm. The sample was injected using a 20 μl fixed loop and the total run time was 45 min. The retention times were found as 25.945, 24.685, 23.83, 10.53, 5.11 and 3.48 min for IMP-1, IMP-2, IMP-3, AMP, IMP-4 and IMP-5 respectively. The linear ranges were found to be 50-150, 0.1- 2.25, 0.1- 2.25, 0.07- 2.25, 0.09- 2.25 and 0.25- 2.25 μg/ml for AMP, IMP-1, IMP-2, IMP-3, IMP-4 and IMP-5 respectively. The mean recovery values were found to be 98.52-100.44% for AMD and its impurities. The degradation rate of AMB in acid, base, peroxide (Oxidative) thermal and photolytic degradation processes was found in range 7-22%. The developed analytical method has been validated according to ICH guidelines. All the degradation products obtained by stress conditions were found to be well separated from the principal peak. The developed method was successfully employed for routine quality control and stability analysis of AMB in pharmaceutical dosage forms.
Loading....