부산대학교 도서관

N-nitrosamines including N-nitrosodimethylamine (NDMA) are classified as potentially carcinogenic substances in humans by the International Agency for Research on Cancer (IARC). In our previous study, we established solvent free headspace – gas chromatography – mass spectrometry (HS-GC-MS) applying stable - isotope dillution analysis method for determination of nine N-nitrosamines in various active pharmaceutical ingredient (APIs) and drug products. However, we observed huge amount of NDMA in some of drugs such as metformin, nizatidine and ranitidine due to in situ formation exposed to high temperature in HS-GC-MS system. This can lead to overestimation and low reproducibility of NDMA quantification results. To overcome the artefactual formation of NDMA during high temperature GC/MS analysis, we developed a method to prevent NDMA in situ formation in APIs by adding nitrite scavenger that can remove nitrite and nitrate. Nitrite and nitrate present in pharmaceuticals reacts with dimethylamine (DMA) to potentially form artefactual NDMA. In this study, nitrite scavengers were applied to reduce the NDMA in situ formation in API. Among the various nitrosation inhibitors, ascorbic acid, caffeic acid, and cysteine were examined for the prevention of artefactual formation of nitrosamines. For optimization of headspce GC/MS conditions, the type of dilution solvent, each scavenger reagent concentration, spiking capacity, and amount of sample were tested. Established HS-GC/MS method will be useful for accurate quantification of N-nitrosamines in a variety of APIs and drug products to reduce the NDMA in situ formation.