Identification and Synthesis of Potential Impurities of Losartan Potassium - A Non-peptide Angiotensinogen II Receptor Antagonist†

Abstract

In the process for the preparation of 1, identified four potential impurities ranging from 0.05-0.15 % were detected in HPLC. Based on the mass spectral data obtained by LC-MS analysis structure of these impurities were characterized as potassium salt of 2-n-butyl-5-chloro-4-hydroxymethyl-1-[(2'-(2H-tetrazole-5-yl)-1,1'-biphenyl-4-yl)methyl]-1H-imidazol (Imp-A, Isolosartan potassium), potassium salt of 5-(4'-methyl-1,1'-biphenyl-2yl)-2H-tetrazole (Imp-B, biphenyl tetrazole analogue of 1), 2-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl)-4-yl]methyl]-1H-imidazole-5-ethanoate (Imp-C, ester analogue of 1) and 2-n-butyl-4-chloro-1-[[2'-(1H-tetrazol-5-yl)-1,1'-biphenyl)-4-yl]-5-triphenyl methoxy methyl-1H-imidazole (Imp-D, o-trityl losartan). These impurities were synthesized from an unambiguous route, confirmed the structure by collecting various spectral data and coinjected with 1, retention time is matching with expected impurities. To our knowledge the impurities A-D were not reported as process impurities elsewhere.