Quantitative identification of halo-methyl-benzoquinones as disinfection byproducts in drinking water using a pseudo-targeted LC-MS/MS method

•Pseudo-targeted LC-MS/MS method was established to analyze HBQs without standards.•Relationship between the ΔG and the ionization efficiency was developed to quantify.•33 HMBQs can be quantified by the newly developed pseudo-targeted LC-MS/MS method.•HMBQs in drinking water were at comparable concentrations as non-methyl-HBQs.•HMBQs cytotoxicity to CHO-K1 cells was higher than that of non-methyl-HBQs. Halobenzoquinones (HBQs) as disinfection byproducts (DBPs) in drinking water is prioritized for research due to their prevalent occurrence and high toxicity. However, only fifteen HBQs can be identified among a high diversity using targeted LC-MS/MS analysis in previous studies due to the lack of chemical standards. In this study, we developed a pseudo-targeted LC-MS/MS method for detecting and quantifying diverse HBQs. Distinct fragment characteristics of HBQs was observed according to the halogen substituent effects, and extended to the development of a multiple-reaction-monitoring (MRM) method for the quantification of the 46 HBQs that were observed in simulated drinking water using non-targeted analysis. The fragmentation mechanism was supported by the changes of Gibbs free energy (ΔG), and a linear relationship between the ΔG and the ionization efficiency of analytes was developed accordingly for quantification of these 46 HBQs, 30 of which were lack of chemical standards. It is noted that 29 of the 30 newly-identified HBQs were halo-methyl-benzoquinones (HMBQs), which were predicted to be carcinogens related with drinking-water bladder cancer risk and be more toxic than non-methyl HBQs. Using the new method, twelve HMBQs were detected in actual drinking water samples with concentrations up to 100.4 ng/L, 3 times higher than that reported previously. The cytotoxicity in CHO cells of HMBQs was over 1-fold higher than that of non-methyl-HBQs. Therefore, HMBQs are an essential, highly toxic group of HBQs in drinking water, which deserve particular monitoring and control. [Display omitted]