Transformation of iopamidol during chlorination

The transformation of the iodinated X-ray contrast media (ICM) iopamidol, iopromide, iohexol, iomeprol, and diatrizoate was examined in purified water over the pH range from 6.5 to 8.5 in the presence of sodium hypochlorite, monochloramine, and chlorine dioxide. In the presence of aqueous chlorine, only iopamidol was transformed. All other ICM did not show significant reactivity, regardless of the oxidant used. Chlorination of iopamidol followed a second order reaction, with an observed rate constant of up to 0.87 M^-1 s^-1 (±0.021 M^-1 s^-1) at pH 8.5. The hypochlorite anion was identified to be the reactive chlorine species. Iodine was released during the transformation of iopamidol, and was mainly oxidized to iodate. Only a small percentage (less than 2% after 24 h) was transformed to known organic iodinated disinfection byproducts (DBPs) of low molecular weight. Some of the iodine was still present in high-molecular weight DBPs. The chemical structures of these DBPs were elucidated via MSⁿ fragmentation and NMR. Side chain cleavage was observed as well as the exchange of iodine by chlorine. An overall transformation pathway was proposed for the degradation of iopamidol. CHO cell chronic cytotoxicity tests indicate that chlorination of iopamidol generates a toxic mixture of high molecular weight DBPs (LC₅₀ 332 ng/μL).