Development and Validation of an Analytical Method for the Identification of 2-Nitrophenyl (phenyl)sulfane as Potential Genotoxic Impurity of Quetiapine Fumarate at Trace Levels by High-Performance Thin-Layer Chromatography

Abstract

Genotoxic impurities can be described as impurities that can induce genetic mutations and chromosomal breaks, or that damage the genetic information within a cell, which may lead to cancer. The European Medical Agency (EMA) and the United States Food and Drug Administration (US FDA) have set a threshold of toxicological concern (TTC) of genotoxic impurities 1.5 μg per day. In a continuous effort to develop an analytical method for the estimation of genotoxic impurities in quetiapine fumarate, a sensitive, simple, and precise high-performance thin-layer chromatography method has been developed and validated for the determination of 2-nitrophenyl( phenyl)sulfane as a genotoxic impurity at trace levels. The limits of detection (LOD) for quetiapine fumarate and 2-nitrophenyl( phenyl)sulfane were found to be 5.11 and 15.5 ng per band, whereas the limits of quantification (LOQ) were observed 0.09 and 0.3 ng per band, respectively. The calibration curve for 2-nitrophenyl( phenyl)sulfane was linear over the concentration range of 10 to 50 ng per band. The method was found to be specific, precise, linear, and accurate for the estimation of 2-nitrophenyl(phenyl)sulfane at trace levels in quetiapine fumarate.