Novel Derivative RP-HPLC Method for Quantification of Dimethyl Sulfate in Capecitabine Drug Substance

Abstract

This study describes the development and quantification of reverse phase HPLC method for the genotoxic impurity i.e. Dimethyl sulfate. It is a key raw material for the synthesis of Capecitabine product. There is no method is available for the determination of Dimethyl sulfate in any active pharmaceutical ingredients. After several development trials, dimethyl sulfate quantification at extremely low level was accomplished on Kromasil C18, 250mm x 4.6mm x 3.5µm column using water and acetonitrile as mobile phases. The flow was selected as 1.0mL/min and temperature of column was maintained at 35°C. Detection wavelength was 330nm and injection volume was 40µL. The LOD and LOQ values were 0.13ppm and 0.45ppm respectively. The method was validated and found to be precise, accurate and robust. The method can be used for determination of Dimethyl sulfate, which is the key starting material for preparation of Capecitabine.