Nitrosamine formation and scavenging in drug products

Abstract

Nitrosamines are considered potential mutagens in the absence of toxicological data and need to be controlled in nanogram quantities in medicinal products. In the case that a medicinal product contains a primary source of vulnerable amines, it would be desirable to have an inhibitor (nitrite scavenger) of nitrosamine formation that can be added to a formulation. Wet granulation has been identified as a critical process step in drug manufacture, this was simulated in this work.The nitrosamine formation was monitored using two systems. On the one hand, an HPLC UV/VIS analysis was implemented to monitor the nitrite level, on the other hand the nitrosamine content was detected using a Triple Quadrupole LC/MS analysis. The rate constant of nitrosation was obtained by regression of measured nitrite concentrations. Based on the results, the nitrite decomposition in water at different pH and temperature should be modelled in a mathematical model like MatLab