정승진 (중앙대학교 약학대학)

이동규 (중앙대학교 약학대학)

정승진 (중앙대학교 약학대학)

이동규 (중앙대학교 약학대학)

Genotoxic nitrosamine impurities, recognized as potential human carcinogens, have been increasingly found in drug substances and drug products. This growing concern emphasizes the urgent need for highly sensitive and reliable analytical methods to ensure safety and regulatory compliance. This study proposes an efficient headspace solid-phase microextraction (HS-SPME) method combined with gas chromatography-tandem mass spectrometry (GC-MS/MS) for the simultaneous analysis of 12 genotoxic nitrosamine impurities. The method was optimized by comparing two types of HS-SPME fibers, with the CAR/DVB/PDMS fiber ultimately selected for its superior extraction performance. HS-SPME parameters, such as extraction solvent and temperature, were systematically optimized to enhance method performance. In order to minimize the formation of thermal artifacts, which are commonly observed at high temperatures, ambient temperature extraction was specifically employed. Moreover, SPME enabled simplified sample preparation with minimal pre-processing and high efficiency. The method was validated following ICH Q2(R1), evaluating the method’s selectivity, sensitivity, accuracy, precision and robustness. This research was supported by a grant (23194MFDS086) from Ministry of Food and Drug Safety in 2025.

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