Carbon, Hydrogen, and Nitrogen Isotope Fractionation Trends in N-Nitrosodimethylamine Reflect the Formation Pathway during Chloramination of Tertiary Amines

Assessing the precursors and reactions leading to the carcinogenic N-nitrosodimethylamine (NDMA) during drinking water disinfection is a major challenge. Here, we investigate whether changes of C-13/C-12,H-2/H-1, and N-15/N-14 ratios of NDMA give rise to isotope fractionation trends that can be used to infer NDMA formation pathways. We carried out compound specific isotope analysis (CSIA) of NDMA during chloramination of four tertiary amines that produce NDMA at high yields, namely ranitidine, 5-(dimethylaminomethyl)furfuryl alcohol, N,N-dimethylthiophene-2-methylamine, and N,N-dimethylbenzylamine. Carbon and hydrogen isotope ratios of NDMA function as fingerprints of the N(CH3)(2) moiety and exhibit only minor isotope fractionation during the disinfection process. Nitrogen isotope ratios showed that NH2Cl is the source of the N atom of the nitroso group. The large enrichment of N-15 in NDMA was indicative of the isotope effects pertinent to bond-cleavage and bond-formation reactions during chloramination of the tertiary amines. Correlation of delta N-15 versus delta C-13 values of NDMA resulted in trend lines that were not affected by the type of tertiary amine and treatment conditions, suggesting that the observed C and N isotope fractionation in NDMA may be diagnostic for NDMA precursors and formation pathways during chloramination.