Nitrosamines and their precursors in pharmaceutical packaging and potential contamination for stability chambers.

N-nitrosamine contamination originating from polymer-based packaging materials is an emerging concern, yet amine precursors in these materials or their contribution to nitrosamine formation are not well characterized. In this study, an SPE-LC-MS/MS method was developed to quantify amines in polymer raw materials used for large volume parenteral (LVP) packaging. Amines were detected in these polymer materials with a linear correlation between amine and nitrosamine levels, indicating that amine precursor content in the packaging itself may play an important role for nitrosamine formation. Since such precursors can migrate or react during LVP's shelf life, predictive stability studies were conducted on LVP stored in stability chambers. The results indicated that N-Nitrosodimethylamine levels were markedly higher in stability chamber compared to warehouse storage. These findings indicated that it might be beneficial to control nitrosamine precursors in polymer and conventional stability studies may not fully represent real-world nitrosamine risks.