Use of orbitrap-MS/MS and QSAR analyses to estimate mutagenic transformation products of iopamidol generated during ozonation and chlorination

The effects of two water purification processes (ozonation, and chlorination after ozonation) on the mutagenicity of a solution containing iopamidol (X-ray contrast medium) were investigated by using the Ames assay. No mutagenicity was observed during ozonation. In contrast, mutagenicity was induced by the ozone-treated iopamidol-containing solution after subsequent chlorination, indicating that mutagenic transformation-products (TPs) were generated. Ten of 70 peaks detected on the LC/MS total ion chromatogram (TIC) of the ozone-treated iopamidol-containing solution after chlorination had a positive correlation (r(2) > 0.6) between their peak areas and the observed mutagenicity, suggesting that TPs detected as these peaks may induce mutagenicity. To narrow down the possible contributors to the observed mutagenicity, we compared the areas of the peaks on the TIC-charts with and without chlorination. Of the ten peaks, six were also detected in the ozone-treated iopamidol-containing solution without chlorination, which did not induce mutagenicity, indicating that these peaks were not related to the observed mutagenicity. Accurate m/z values and MS/MS analysis with an orbitrap MS of the remaining four peaks revealed that two of them represented the same TP in the negative and positive ion modes. The three remaining TPs were assessed in four quantitative structure activity relationship models for predicting Ames mutagenicity. At least one model predicted that two of the three TPs were mutagenic, whereas none of the models predicted that the other TP was a mutagen, suggesting that the former TPs, estimated as N1-acetyl-5-amino-6-chloro-2-iodobenzene-1,3-dicarboxamide and 3-hydroxy-243-[(2-hydroxyethoxy)carbony1]-2,4,6-triiodo-5-nitrobenzoyl}amino)propanoic acid, could be the candidate compounds that contributed to the observed mutagenicity. (C) 2016 Elsevier Ltd. All rights reserved.