Isolation and structural elucidation of novel degradant during degradation study of Azilsartan kamedoxomil

Abstract

To investigate the stability of Azilsartan kamedoxomil (AKM) under stress conditions and to identify the degradation products, it was subjected to force degradation/stress under basic, acidic, oxidative, thermal, humidity, and photolytic conditions as per international council for harmonisation (ICH) guidelines. AKM degradation was found under basic, acidic, oxidative, thermal, photolytic, and humidity stress. Separation of the four degradation products of AKM was carried out utilizing a C-18 column, employing preparative High-performance liquid chromatography (HPLC) and gradient mode elution. The structures were elucidated with spectroscopic HRMS, 1D, and 2D NMR and the products were identified as 2-hydroxy-1-[[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol −3-yl)[1,1′-biphenyl]-4-yl]-methyl]-1 H-benzimidazole-7-carboxylic acid (AKMDP-1), 2-ethoxy-1-[[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)biphenyl-4-yl]methyl]-1 H-benzimidazole-7-carboxylic acid (AKMDP-2), (5-methyl-2-oxo-1,3-dioxol-4-yl)methyl 2-hydroxy-1-[[2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)[1,1′-biphenyl]-4-yl]methyl]-1 H-benzimidazole-7-carboxylate (AKMDP-3) and 2-hydroxy-3-oxobutyl 2-ethoxy-1-((2′-(5-oxo-4,5-dihydro-1,2,4-oxadiazol-3-yl)-[1,1′-biphenyl]-4-yl)methyl)-1 H-benzo[d]imidazole-7-carboxylate (AKMDP-4). Out of them, two degradants AKMDP-1 and AKMDP-3 were reported earlier, AKMDP-2 was one of the process intermediate (Azilsartan) used in the preparation of Azilsartan kamedoxomil.