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

Bhupendrasinh Vaghela

doi:10.3797/scipharm.1111-07

Abstract

A novel stability-indicating gradient RP-UPLC method was developed for the quantitative determination of process related impurities and forced degradation products of fexofenadine HCl in pharmaceutical formulations. The method was developed by using Waters Aquity BEH C18 (100 mm x 2.1 mm) 1.7 μm 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°C and detection wavelength at 220nm. Fexofenadine HCl was subjected to the stress conditions including oxidative, acid, base, hydrolytic, thermal and photolytic degradation. Fexofenadine HCl was found to degrade significantly in oxidative stress conditions, and degradation product was identified and characterized by ESI-MS/MS, 1H and 13C 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.

Highlights

Fexofenadine, 2-[4-(1-hydroxy-4-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}butyl)phenyl]2-methylpropanoic acid (Fig. 1), is a highly selective peripheral histamine H1 receptor antagonist used in the treatment of allergic diseases such as allergic rhinitis and chronic urticaria
Stress studies were performed at 1200μg/mL concentration of fexofenadine HCl on tablets to provide an indication of the stability-indicating property and specificity of proposed method
An unknown impurity with relative retention time (RRT) 0.71 with respect to fexofenadine was observed during oxidative degradation study

Summary

Introduction

Fexofenadine, 2-[4-(1-hydroxy-4-{4-[hydroxy(diphenyl)methyl]piperidin-1-yl}butyl)phenyl]2-methylpropanoic acid (Fig. 1), is a highly selective peripheral histamine H1 receptor antagonist used in the treatment of allergic diseases such as allergic rhinitis and chronic urticaria. Fexofenadine is the active derivative of the antihistamine terfenadine, with no anti-chrolinergic or alpha 1-adernergic receptor-blocking effects and without severe cardiac side effects of terfenadine [1, 2]. HO O OH N Fexofenadine O OH HO N Impurity-A Impurity-C Fig. 1

Methods

Results

Conclusion