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 13 C/ 12 C, 2 H/ 1 H, and 15 N/ 14 N 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(CH 3 ) 2 moiety and exhibit only minor isotope fractionation during the disinfection process. Nitrogen isotope ratios showed that NH 2 Cl is the source of the N atom of the nitroso group. The large enrichment of 15 N in NDMA was indicative of the isotope effects pertinent to bond-cleavage and bond-formation reactions during chloramination of the tertiary amines. Correlation of δ 15 N versus δ 13 C 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.