title: Forced degradation, LC-UV, MS(n) and LC-MS-TOF studies on azilsartan: Identification of a known and three new degradation impurities.
abstract: 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 (250mm×4.6mm; 5μ) with isocratic elution using mobile phase composed of ammonium formate (20mM, pH 3.0), methanol and acetonitrile (40:5:40% v/v), at a flow rate of 0.8mlmin(-1) at ambient temperature. The products were characterized through +ESI-MS(n) 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.
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India.
authors.forename: Dhiraj
authors.initials: D
authors.lastname: Kaushik
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India.
authors.forename: Jasmeen
authors.initials: J
authors.lastname: Kaur
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India.
authors.forename: Vaneet
authors.initials: V
authors.lastname: Paul Kaur
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India.
authors.forename: Balraj
authors.initials: B
authors.lastname: Saini
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India.
authors.forename: Yogita
authors.initials: Y
authors.lastname: Bansal
authors.affiliation: Department of Pharmaceutical Sciences and Drug Research, Punjabi University, Patiala - 147002, India. Electronic address: gulshanbansal@rediffmail.com.
authors.forename: Gulshan
authors.initials: G
authors.lastname: Bansal
mesh_terms: D001562:Benzimidazoles / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D002853:Chromatography, Liquid / Q000379:methods; D004340:Drug Contamination; D010069:Oxadiazoles / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*; D013056:Spectrophotometry, Ultraviolet / Q000379:methods; D053719:Tandem Mass Spectrometry / Q000379:methods*
chemical_list: D001562:Benzimidazoles; D010069:Oxadiazoles; C521273:azilsartan
keywords: Azilsartan medoxomil; Forced degradation; Impurities; LC–MS–TOF; Mass fragmentation