Role of ranitidine in N-nitrosodimethylamine formation during chloramination of competing micropollutants

Ranitidine (RNT) is a widely known precursor of N-nitrosodimethylamine (NDMA) as evinced by the self-catalytic formation of NDMA during chloramination. In the present study, the NDMA formation potentials (NDMA-FP) of 26 micropollutants were assessed, particularly when mixed with RNT. 11 compounds were identified as individual precursors, including trimebutine and cimetidine, which exhibited substantial NDMA-FP, with up to 10% molar yield. In addition, nitrosamines, other than NDMA, namely N-nitrosodiethylamine and N-nitrosomethylamine, were observed from diethylamine-containing precursors, such as metoclopramide. In a 1:1 mixture of RNT and a competitor, the change in NDMA-FP was mostly comparable (within 20% deviation), while antagonistic interactions were observed for competitors, such as diethylhydroxylamine. The scattered overall NDMA-FP should be considered as a product of competition among the precursors for core substrates and intermediates for NDMA formation. The co-existence of either trimebutine or metoclopramide with RNT led to an exceptionally synergetic NDMA generation. Degradation kinetics and chlorination/nitrosation experiments combined with mass spectroscopy analyses indicated that RNT would accelerate both the initial chlorination and nitrosation of trimebutine and metoclopramide, leading to N-nitroso complexes, which have well-understood NDMA formation pathways, i.e., amination with subsequent aminyl radical generation. This work demonstrates a wide array of precursors with NDMA-FP, suggesting that nitrosamine formation is potentially underestimated in field environments.