Isolation, Characterization and Cumulative Quantification approach for nine organic impurities in empagliflozin and linagliptin drugs

Abstract

Aim of the study was to identify impurities from linagliptin and empagliflozin. By using ¹H NMR, ¹³C, LC-MS, preparative, and analytical HPLC, impurities were identified. To identify and quantify contaminants, a novel HPLC method has been validated. A gradient programme was used to separate four linagliptin impurities and five empagliflozin impurities, process-related and degradation impurities that which were produced under stress, on the ACE PFP C18 column. Mobile phase A was acetonitrile and 0.1% orthophosphoric acid. As the mobile phase B, methanol and acetonitrile were combined in a 10:90 volume ratio. Pump flow was adjusted to 1.0 mL/ min and 230nm wavelength was chosen at 40°C column oven temperature. During stress conditions, acid, humid, base, ultraviolet light, thermal, and oxidative were carried out. The separation was achieved between the peaks and degradation products. method was validated with respect to current ICH guidelines for solution stability, specificity, linearity, ruggedness, precision, accuracy, and robustness. Preparative HPLC was used to isolate two unknown impurities, which were then identified using LC-MS, ¹H NMR, and ¹³C. Based on literature, The first research study to propose nine impurities in mixed dosage forms of linagliptin and empagliflozin with quantifying method.