Minkyeong Hong (Chung-Ang University)

Dong-Kyu Lee (Chung-Ang University)

Minkyeong Hong (Chung-Ang University)

Minki Shim (Chung-Ang University)

Dong-Kyu Lee (Chung-Ang University)

Nitrosamine impurities have emerged as a significant concern in the pharmaceutical industry. Among them, nitrosamine drug substance-related impurities (NDSRIs) have drawn particular attention. Nortriptyline, a widely used antidepressant, has been identified as a potential source of NDSRI formation. In this study, a quantification method for N-nitroso-nortriptyline in nortriptyline products was established, offering broad applicability in both industrial and academic settings. Liquid chromatography-mass spectrometry (LC-MS), was employed in order to separate and quantify nortriptyline and its related impurities. The evaluation of various chromatographic columns resulted in the successful separation of trace levels of N-nitroso-nortriptyline from the active pharmaceutical ingredient. The application of an ESI source resulted in optimal detectability for both nortriptyline and N-nitroso-nortriptyline. The developed method was subjected to comprehensive validation, successfully meeting all essential criteria, including accuracy, precision, selectivity, and linearity. It is important to note that the method's sensitivity, as indicated by its limit of quantification, is sufficient to confirm that the exposure to N-nitroso-nortriptyline from the antidepressant tablet remains below the acceptable intake (AI) threshold of 8 ng/day. This research was supported by a grant (23194MFDS086) from Ministry of Food and Drug Safety in 2025.