Experimental characterization of N-nitrosamine formation through kinetic modeling and LC-MS/MS analytical methods

Description

Nitrosamines are formed through the reaction between nitrosating agents (NOX) and secondary amines (R2NH). The formation of NAs, through a nitrosation reaction involving NaNO2 in aqueous acidic environments (pH 2-5), is driven by the in-situ formation of unstable nitrous acid (HNO2). However, many variables can influence the identity of the final NA formed as well as the primary nitrosating agent involved in the formation. Factors such as pH, concentration of HNO2 generated in situ, and the presence and strength of nucleophiles. Under highly acidic conditions, nitrosonium ions can form and react with nucleophilic secondary amines to produce NAs. In moderately acidic environments, H2NO2+ serves as the primary nitrosating agent in the presence of strong nucleophiles. Here, nucleophilic attack on the nitrogen of the nitrosonium electrophile results in NAs formation. When nucleophiles are absent and HNO2 concentrations are high, nitrite ions act as nucleophiles, leading to the formation of N2O3 as the nitrosating agent. The characterization of the reactions that result in formation of the TCNAs have not been well established, including the behavior of this reaction in aqueous solution, liquid model systems and final product models. This thesis aims to better characterize the formation of TCNAs in simple aqueous solution models, starting with the reaction between NaNO2 and piperidine in the formation of N-nitrosopiperidine (NPIP). Parameters including pH, temperature, varying concentrations of reaction precursors as well as catalysts and/or inhibitors will be investigated. This work will establish nitrosation rate constants, equilibrium constants and experimentally validate predictive models that aim to forecast the rate of NPIP formation under different conditions. The experimental characterization of this reaction will then be extended to the formation of the TCNAs, in aqueous environments and liquid protein models, with the ultimate goal of building experimentally validated predictive models in the formation of TCNAs under varying conditions.

Period	27 Jan 2025 → 27 Jun 2025
Degree of Recognition	International