Isolation and structural characterization of two novel oxidative degradation products of losartan potassium active pharmaceutical ingredient using advanced analytical techniques

Abstract

Rationale Losartan potassium (losartan) is the most frequently utilized antihypertensive medication in the world. However, partial oxidation of losartan produces toxic by‐products that could be harmful to living organisms. Therefore, it is necessary to degrade the losartan and identify the potential toxic oxidative degradation products to minimize their formation during manufacturing, formulation, storage, and packing conditions. Methods Oxidative degradation experiments of losartan were performed according to ICH guidelines. The degradation products were detected using ultra‐high‐performance liquid chromatography–mass spectrometry analysis, isolated by using preparative HPLC, and identified by using high‐resolution mass spectrometry and nuclear magnetic resonance spectroscopic techniques. Results The degradation products (DP‐1, DP‐2, and DP‐3) were identified as (((2'‐(2H‐tetrazol‐5‐yl)‐[1,1'‐biphenyl]‐4‐yl)methyl)amino)‐2‐oxoethylpentanoate, 5‐(4'‐((2 butyl‐4‐chloro‐5‐(hydroxymethyl)‐1H‐imidazol‐1‐yl)methyl)‐[1,1'‐biphenyl]‐2‐yl)‐1H tetrazol‐1‐ol, and 5‐(4'‐((2‐butyl‐4‐chloro‐5‐(hydroxymethyl)‐1H‐imidazol‐1 yl)methyl)‐[1,1'‐biphenyl]‐2‐yl)‐2H‐tetrazol‐2‐ol, respectively. Conclusions Forced degradation of losartan potassium API under oxidative condition indicates the formation of two major novel oxidative degradation products (DP‐2 and DP‐3) and one minor known degradation product (DP‐1).Preparative HPLC used for the isolation of the resultant DPs and their structures were successfully established using UHPLC–MS, 1H NMR, 13C NMR, HSQC, HMBC, and HRMS spectroscopic techniques.

Prediction of Degradation Profiles for Various Sartans under Solvent-Free Mechanochemical Conditions

“…Singamsetti and co-workers studied the stability of LOS by treating LOS with H 2 O 2 for 4 h at room temperature, while, as mentioned before, Pandey et al investigated its stability by adding a HCl solution at 60 °C for 24 h. , In the untreated sample of LOS , five impurities were structurally identified (Figure ). LOS-1 (Figure , Table S6-B), bearing a formyl group, is also described as related compound K in PhEur…”