Isolation, Characterization and Cumulative Quantification Approach for Nine Organic Impurities in Empagliflozin and Linagliptin Drugs

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