Trace Level Determination of Potential Genotoxic Impurities in Quetiapine fumarate by Liquid Chromatography-Mass Spectrometry.

A novel liquid chromatography mass spectrometry method was developed and validated to determine three potential genotoxic impurities, namely 2-(2-Aminophenylthio)benzoicacid hydrochloride, 2-Aminothiophenol and 2-(2-Aminophenylthio)benzonitrile, at trace level (about 1.6 ppm) in Quetiapine fumarate drug substance, an antipsychotic drug. Since these impurities are potentially Genotoxic, should be controlled at or below specific acceptance limits. The column was Inert sustain-AQ C18, 250x4.6 mm, 5μm in reversed-phase mode with column temperature at 45°C. The mobile phase was 0.1% Trifluoroacetic acid in water, acetonitrile with gradient elution mode and the run time of 45 minutes. The flow rate was 0.8 mL/min. The mass spectrometer was used to quantify the amount of impurities using electrospray ionization mode at specific m/z 245.9, 126.0 and 226.9 for 2-(2-Aminophenylthio)benzoicacid hydrochloride, 2-Aminothiophenol and 2-(2-Aminophenylthio) benzonitrile respectively. The method was found to be sensitive and having excellent linearity in the concentration ranges from limit of quantification to 150% of the permitted level (0.47 μg/mL to 2.36 μg/mL) with correlation coefficients above 0.999. The results showed that the method was found to be specific, precise, linear and accurate for the estimation of these three impurities in Quetiapine fumarate.