Forced degradation, LC–UV, MSn and LC–MS–TOF studies on azilsartan: Identification of a known and three new degradation impurities

• Forced degradation studies were carried out on azilsartan according to ICH guidelines.
• Four degradation products were formed under acidic, basic and neutral hydrolysis.
• All degradation products were characterized through LC–UV, LC–MS–TOF and MSn studies.
• Mechanisms and pathways of azilsartan degradation discussed and outlined.

In the present study, Azilsartan (AZL) was subjected to ICH recommended forced degradation conditions of hydrolysis, oxidation, dry heat and photolysis. The drug degraded to four degradation products (I–IV) under acidic, alkaline and water hydrolysis and photolysis. All the four degradation products were resolved in a single run on a C-18 column (250 mm × 4.6 mm; 5 μ) with isocratic elution using mobile phase composed of ammonium formate (20 mM, pH 3.0), methanol and acetonitrile (40:5:40% v/v), at a flow rate of 0.8 ml  min−1 at ambient temperature. The products were characterized through +ESI–MSn spectra of AZL and LC–MS–TOF studies as 2-ethoxy-3H-benzo-imidazole-4-carboxylic acid (I), 2-hydroxy-3-[2′-(5-oxo-4,5-dihydro-[1,2,4]oxadiazol-4-ylmethyl]-3H-benzoimidazole-4-carboxylic acid (II, deethylated AZL), 3-[2′-(1H-diazirin-3-yl)-biphenyl]-4-ylmethyl]-2-ethoxy-3H-benzoimidazole-4-carboxylic acid (III), and 3-[4′-(2-ethoxy-benzo-imidazol-1-ylmethyl)-biphenyl-2-yl]-4H-[1,2,4]oxadiazol-5-one (IV, decarboxylated AZL). Product I was found to be a known process related impurity whereas the products II–IV were identified as new degradation impurities. The most probable mechanisms for formation of these degradation products were proposed.

Four degradation products of Azilsartan formed under different ICH prescribed forced degradation conditions, are characterized through LC–UV, MSn and LC–MS–TOF studies.Figure optionsDownload as PowerPoint slide