Identification of genotoxic impurities and trace level determination of nitrosamine impurities in recycled recovery solvents by using gas chromatography-tandem mass spectrometry method and advantages of re-usage of recycled recovery solvents for sust

Abstract

The research article aims to identify unknown impurities in recycled recovery solvents, with a focus on potential genotoxic and Nitrosamine impurities. Pharmaceutical industries are increasingly using recycled recovery solvents in drug manufacturing to promote sustainability, but there are concerns about the formation of impurities. To address this issue, a case study was conducted on 10th cycle of recycled recovery solvents Methylene chloride, Ethyl acetate, and Toluene to identify the unknown impurities as well as trace level determination of nitrosamine impurities which used in the manufacturing process of Bupropion hydrochloride. The study was initiated by using common solvent method in these recycled recovery solvents and observed some unknown impurities. These unknown impurities were analyzed to identify whether they are genotoxic or non-genotoxic by using validated GC–MS/MS method. One genotoxic impurity, Ethyl chloride was identified. Further, based on structural characterization or manufacturing process or long-term storage, the recovery solvents were analyzed by using a developed and validated a gas chromatography with triple-quadruple mass spectrometry (GC–MS/MS) method to quantify the five nitrosamine impurities (NDMA, NDEA, NEIPA, NDIPA, and NDBA) in these solvents. This method capable to detect the five nitrosamine impurities at a level of 1.2 ppb for limit of detection and 3.0 ppb for limit of quantitation with respect to sample concentration of 500 mg/mL. Overall, this research highlights the importance of systematic analysis and establishment of cycles for re-usage of recovery solvents to ensure public health, safety in pharmaceutical manufacturing, to reduce the carbon footprint and to promote sustainable development.