The detection and quantification of nitrosamine impurities in pharmaceutical materials has become a topic of global concern in recent years. Nitrosamine analysis is challenging and requires the application of highly selective and sensitive analytical techniques, capable of quantification in the low ppb range. This white paper discusses how LC-MS/MS methods can be developed and applied to the determination of a range of nitrosamine impurities, highlighted by regulatory authorities, in pharmaceutical APIs.
Additionally, the impact of isobaric interference from N,N-dimethylformamide (DMF), which may co-elute with and result in over-quantification of NDMA, is assessed. Varying the LC stationary phase chemistry to improve chromatographic retention and resolution of NDMA and DMF, along with considered selection of appropriate MRM transitions, was found to provide a solution to improve NDMA quantification accuracy.