A Novel Validated GC-MS/MS Method for the Estimation of five Genotoxic impurities in Bupropion Hydrobromide.
The detection of trace levels of genotoxic impurities (GTIs) in pharmaceutical products requires the use of analytical methodologies that are precise, accurate, and highly sensitive for effective analysis and control. As per route of synthesis of Bupropion Hydrobromide drug substance, there is a possibility of formation of genotoxic impurities form the key staring material 3’-chloro propiophenone. Hence, conducted CASE Ultra test (QSAR prediction methodologies) and identified five new genotoxic impurities. These genotoxic impurities were named as “2-bromo-1-(2',3'-dichloro phenyl) propan-1-one, 2-bromo-1-(2'-chlorophenyl) propan-1-one, 2-bromo-1-(4'-chlorophenyl) propan-1-one, 2-bromo-1-(3',4'-dichloro phenyl) propan-1-one and 2-bromo-1-(3',5'-dichloro phenyl) propan-1-one”.These genotoxic impurities are necessary to quantify and to identify in the Bupropion derivatives due to the carcinogenic in nature. Hence, developed and validated a Novel, sensitivity and highly precise gas chromatography-mass spectrometry (GC–MS/MS) technique by following ICH guidelines. The separation of genotoxic impurities were performed using DB-35, which measured 30 meters in length, had a diameter of 320μm, and a film thickness of 0.5μm. The Limit of detection and limit of Quantitation was observed 0.01 ppm and 0.03 ppm respectively. The correlation coefficient value for the linearity found more than 0.995 for all five Genotoxic impurities. The average recovery for all impurities was observed in-between 95%-110%. This method, which has been developed and validated, has not been documented in any of the literature. Furthermore, the currently available methods are inadequate for the detection of genotoxic impurities in Bupropion derivatives at trace levels. Therefore, the method established in this study employs a more precise analytical technique utilizing mass spectrometry for the detection of trace levels of genotoxic impurities.