Identification and Characterization of an Oxidative Degradation Product of Fexofenadine, Development and Validation of a Stability-Indicating RP-UPLC Method for the Estimation of Process Related Impurities and Degradation Products of Fexofenadine in Pharmaceutical Formulations

摘要

A novel stability-indicating gradient RP-UPLC method was developed for the quantitative determination of process related impurities and forced degradation products of fexofenadine HCI in pharmaceutical formulations. The method was developed by using Waters Aquity BEH C18 (100 mm × 2.1 mm) 1.7 urn column with mobile phase containing a gradient mixture of solvent A (0.05% triethyl amine, pH adjusted to 7.0 with ortho-phosphoric acid) and B (10:90 v/v mixture of water and acetonitrile). The flow rate of mobile phase was 0.4 mL/min with column temperature of 30℃ and detection wavelength at 220nm. Fexofenadine HCI was subjected to the stress conditions including oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Fexofenadine HCI was found to degrade significantly in oxidative stress conditions, and degradation product was identified and characterized by ESI-MS/MS, ~1H and ~（13）C NMR spectroscopic method as the N-oxide 2-[4-(1-hydroxy-4-{4-[hydroxy(diphenyl)methyl]-1-oxido piperidin-1-yl}butyl)phenyl]-2-methylpropanoic acid. The degradation products were well resolved from fexofenadine and its impurities. The mass balance was found to be satisfactory in all the stress conditions, thus proving the stability indicating capability of the method. The developed method was validated as per ICH guidelines with respect to specificity, linearity, limit of detection and quantification, accuracy, precision and robustness.