Residual Nitrite Detection by Reactivity-based Probe: Applications in Pharmaceutical Components

Jiyoung Jung

College: Hennings College of Science Mathematics and Technology

Department: Chemistry & Physics

Abstract:

Nitrite can lead to the formation of nitrosamines, which are well-known carcinogens. Consequently, measuring residual nitrite has become a critical step in controlling nitrosamine formation during drug manufacturing. Nitrosamines are formed when reactive secondary amines react with nitrite ions, and while the sources of secondary amines can often be identified, nitrite may originate from various reagents or excipients used in pharmaceutical products. Recently, we developed a probe molecule that reacts selectively with nitrite ions through an intramolecular cyclization reaction. This reaction generates a diazonium intermediate, which subsequently undergoes cyclization with an adjacent phenyl group. Our earlier work provided important insights into the relationship between electronic properties and reactivity. By fine-tuning the functional groups on the phenyl ring, we significantly increased the probe’s sensitivity to nitrite ions. When combined with chromatographic separation and mass detection, this method enables interference-free and highly accurate measurement. Using this approach, we demonstrated that the probe can reliably detect residual nitrite in various pharmaceutical excipients, providing an effective tool to support improved nitrosamine control strategies.