Development and validation of liquid chromatography-tandem mass spectrometry method for the estimation of a potential genotoxic impurity 2-(2-chloroethoxy)ethanol in hydroxyzine.

Abstract

2-(2-Chloroethoxy)ethanol (CEE) belongs to the so-called cohort of concerns which were classified as highly potent mutagenic carcinogens by the World Health Organization. It is widely used in the synthesis of the essential anti-histamine drug hydroxyzine. In addition, it is used as a primary solvent in dyes, nitrocellulose, paints, inks and resins. Owing to its potential genotoxicity, an efficient liquid chromatography-tandem mass spectrometry method was developed for the quantitative estimation of CEE traces in an active pharmaceutical ingredients and in tablet dosage forms of hydroxyzine-free base. The chromatographic separation was achieved on a C18 column using a gradient elution mode with a binary solvent system (ammonium formate and methanol). Mass detection was performed for CEE using a positive mode with selected ion monitoring technique at m/z value of [M + NH4 ]+ . The developed method was validated as per the International Conference on Harmonizaiton guidelines. The quantitation limit, linearity and recoveries were found to be 0.56 ppm, 0.56-7.49 ppm (r2 > 0.9985) and 93.6-99.3%, respectively. The proposed method was highly compatible and was used effectively to estimate CEE traces in different stages of drug synthesis and in tablet dosage forms of hydroxyzine for routine and stability testing.