Abstract: Microbial contamination of drinking water is still the major cause of water-borne disease affecting millions of people around the world. Disinfection of drinking water is the most effective public health measure to disinfect pathogens to eradicate water-borne diseases. However, disinfection of water unintentionally results in formation of disinfection byproducts (DBPs) from the reactions between disinfectants (e.g. chlorine and chloramines) and natural organic matters (NOM) in water. In order to control drinking water quality, surrogate DBPs such as several trihalomethanes (THMs) and haloacetic acids (HAAs) are currently regulated in the most countries. Epidemiological studies have shown potential association of drinking chlorinated water and increased risk of developing bladder cancer. However, accumulating evidence from past 30 years suggests that the regulated DBPs are not the cause of the increased bladder cancer risk or adverse reproductive effects that have been observed in population studies. Other unidentified, yet more toxic, DBPs may be produced at much lower levels. To address the analytical and bioanalytical challenges in drinking water safety, we have developed a set of liquid chromatography and tandem mass spectrometry techniques for ultra sensitive detection of carcinogens in water. We have discovered some previously unknown DBPs that are likely bladder carcinogens, such as nitrosamines, haloquinones, and chloro-phanazines in drinking water. In the present study, we report tandem mass spectrometry study of DBP-DNA binding as a tool for genotoxicity testing to assist prioritization of DBPs for regulatory consideration.