Quantification of Hydrazine Hydrate in Imatinib Mesylate at Genotoxic Level by Chromatographic Method

Abstract

Hydrazine hydrate has genotoxic effect in nature and so it should be controlled down as Potential Genotoxic Impurity (PGI). Being polar molecule, hydrazine hydrate (N2H4.H2O) has no chromophores present in structure which can follow Lambert beer law, thus it is difficult to analyze. The present work described an accurate and highly sensitive reversed-phase liquid chromatography-UV derivatization method for determination of hydrazine in imatinib mesylate drug substance. The method of quantification was developed by attaching chromophores to hydrazine with derivatization, which helped to increase sensitivity. The derivatization of hydrazine hydrate was performed using 1% methanolic solution of benzaldehyde which acts as derivatizing agent. The derivatized product 1,2-dibenzylidenehydrazine gives maximum absorbance at 300 nm and at this wavelength no interference of solvents and other impurities are noted. Limit of detection for developed method was 0.002 μg/g. The developed method was validated to determine hydrazine content and can be used in quality control for commercial batch release of imatinib mesylate drug substances with a genotoxic specification limit level 1.87 μg/g by HPLC.