Development of an Analytical Method for Identification of the Genotoxic Impurity of Quetiapine Fumarate by High-Performance Thin-Layer Chromatography

Summary Genetic mutations, chromosomal breaks, and chromosomal rearrangements, which are induced due to organic impurities, are considered as potential genotoxic impurities. The European Medicines Agency (EMA) and the United States Food and Drug Administration (US FDA) have set a threshold of toxicological concern (TTC) of 1.5 µg per person per day for each impurity. A sensitive and simple high-performance thin-layer chromatography (HPTLC) method has been developed and validated for determination of the potential genotoxic impurity, namely, 2-chloroaniline, at trace levels in quetiapine fumarate. The method was found to be specific and selective for the application. The limit of detection (LOD) and limit of quantification (LOQ) for quetiapine fumarate were found to be 1.27 and 3.87 ng per band. The LOD and LOQ values for 2-chloroaniline were found 0.018 and 0.054 ng per band, respectively. The calibration curve for 2-chloroaniline was linear over a concentration range from 2.5 to 12.5 ng. The method was found to be specific, precise, linear, and accurate and can be employed for monitoring and estimation of levels of 2-chloroaniline in quetiapine fumarate.