권혁주 (중앙대학교)

한상범 (중앙대학교)

권혁주 (중앙대학교)

한상범 (중앙대학교)

In recent years, the unexpected occurrence of nitrosamines as pharmaceutical impurities has been generating substantial attention from both the public and the pharmaceutical industry, emphasizing the need for effective mitigation strategies during drug manufacturing. According to previous studies, the presence of heat and moisture during wet granulation processes can lead to N-nitrosodimethylamine (NDMA) formation, resulting from a reaction between nitrite impurities in excipients and dimethylamine (DMA) in the API. Therefore, This study aimed to assess the potential of nitrite scavengers in mitigating NDMA formation in metformin formulations. Formulations with single or mixed antioxidants were evaluated for NDMA suppression. Three antioxidants—ascorbic acid, ferulic acid, and α-tocopherol—were selected based on their highly effective nitrite scavenging properties. Each formulation was processed using the acid-added liquid-liquid extraction (LLE) method, followed by the analysis of NDMA using gas chromatography-electron ionization-tandem mass spectrometry (GC-EI-MS/MS). The results demonstrated that ascorbic acid and ferulic acid exhibited significant inhibitory effects even at low concentrations, whereas α-tocopherol exhibited comparatively limited suppression efficiency. This research was supported by a grant(23194MFDS086) from Ministry of Food and Drug Safety in 2025.