The competitive effect of different chlorination disinfection methods and additional inorganic nitrogen on nitrosamine formation from aromatic and heterocyclic amine-containing pharmaceuticals

Abstract

Amine-containing pharmaceuticals formed nitrosamines that are nitrogenous disinfection byproducts of public concerns due to their carcinogenicity. The objective of this study was to investigate the co-effect of additional inorganic nitrogen in different forms (ammonium, nitrite, and nitrate) and different disinfection approaches (chlorination, monochloramination, dichloramination, and two-step chlorination) on eight nitrosamine formation from four widely used pharmaceuticals. N-nitrosodimethylamine (NDMA) was the main species formed. The presence of N-nitrosomethylethylamine (NMEA), nitrosomorpholine (NMor), and N-nitrosopiperidine (NPip) was found in certain experiments. For one-step chlorination, the influential factors, in decreasing order of importance, were the molecular structural characteristics of the pharmaceutical, oxidation method, and presence and form of additional nitrogen. In four pharmaceuticals with comparative structures, the availability of amine intermediates during degradation was the key to higher nitrosamine yields. Monochloramine significantly enhanced nitrosamine formation from four pharmaceuticals. NDMA formation by adding hypochlorous acid and ammonium separately were lower than those during monochloramination. During two-step chlorination, NDMA formation was enhanced at certain pre-chlorine doses (e.g., a Cl/N molar ratio of 20 or 4). The pre-chlorine dose changed the Cl/N ratio. As the ratio was increased, the combined chlorine residual was formed and decreased. When the ratio was high, breakpoint chlorination possibly occurred enhancing NDMA formation. While NDMA formation was successfully inhibited by two-step chlorination, ammonium brought the NDMA yields of these pharmaceuticals back to the range observed in chloramination, suggesting the importance of ammonium control for limiting NDMA formation from pharmaceuticals during two-step chlorination.