Abstract

QUANTIFICATION OF GENOTOXIC IMPURITIES IN FEXOFENADINE HYDROCHLORIDE BY SIMPLE AND SENSITIVE LIQUID CHROMATOGRAPHY TECHNIQUE

Ajit Anerao*, Vishal Solse, Amol More, Nitin Pradhan

ABSTRACT

Fexofenadine hydrochloride is synthesized using two key raw materials Methyl-2-(4- (4-chlorobutanoyl) phenyl)-2-methylpropanoate (KRM-I) and Diphenyl-4-piperiridinemethanol (KRM-II). On basis of structure-activity relationship (SAR) KRM-I is potentially genotoxic impurity. One more mutagenic impurity that is bromobenzene is used for the synthesis of KRM-II. A sensitive High performance liquid chromatography (HPLC) method was developed and validated for the determination of both impurities in the active pharmaceutical ingredient fexofenadine hydrochloride. HPLC column Cosmosil MS-II C18, 250 mm X 4.6 mm, 5 μm particle size with ultra -violet detector (UV) was used. The proposed method is specific, linear, accurate, rugged and precise. The calibration curve of bromobenzene and KRM-I showed good linearity over the concentration range of 1.0μg/g to 12.0μg/g with respect to test solution concentration and the regression coefficient was 0.999 for both analytes. Method had very low limit of detection (LOD) and limit of quantification (LOQ) of both analytes which proves that the method is sensitive and suitable for quantification of both genotoxic impurities at trace level.

Keywords: Fexofenadine; genotoxic impurity; method development and validation.