최연우 (충남대학교 약학대학)

김형민 (충남대학교 약학대학)

최연우 (충남대학교 약학대학)

이주미 (충남대학교 약학대학)

김형민 (충남대학교 약학대학)

  N-nitrosodimethylamine (NDMA) is a genotoxic nitrosamine impurity of regulatory concern in pharmaceutical products. Nizatidine contains a dimethylamine moiety and may form NDMA during storage. However, the effects of storage and packaging conditions on NDMA formation remain unclear. In this study, NDMA formation in nizatidine capsules was evaluated under accelerated conditions (40 ℃/25% RH and 40℃/75% RH) and quantified by LC–MS/MS (APCI, positive MRM mode) using NDMA-d₆ as an internal standard. accelerated conditions included packaging type (HDPE bottles/aluminum aluminum blister), silica gel placement (top, middle and bottom)and loading (0–3 g), and capsule fill quantity. In HDPE bottles, top placement of silica gel above the capsules provided the most effective NDMA suppression. Higher silica gel loading further enhanced this mitigation in a dose-dependent manner, with 3 g showing maximum efficacy at lower capsule fill counts. Conversely, aluminum-aluminum blister packaging exhibited limited NDMA suppression due to the structural inability to incorporate desiccants. Overall, these findings demonstrate that NDMA formation in nizatidine formulations is strongly modulated by storage environments and packaging parameters, and that strategic silica gel deployment (top placement and optimized loading) offers a practical and scalable packaging solution to mitigate nitrosamine risks. This research was supported by a gran(23194MFDS086) from Ministry of Food and Drug Saftey in 2025.