Formation and occurrence of disinfection byproducts of benzodiazepine drug estazolam in drinking water of Beijing

Abstract

Estazolam (EZ) is a long-acting benzodiazepine (BZD) drug with high clinical consumption in China to treat anxiety, depression and other syndromes. Recently, it has been found as a leading potentially inappropriate medication among hospitalized elderly patients, increasing the risk of falls. It is discharged into the aquatic environment after use and has been frequently detected, ultimately affecting the safety of drinking water. In the present study, the reaction of EZ during chlorination disinfection was investigated in detail with regard to its transformation and kinetics. By means of ultra-performance liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UPLC-QTOF-MS), four main disinfection byproducts (DBPs) were tentatively identified, and the transformation pathways were speculated to be cleavage at the imine linkage and oxidation on the diazepinone ring. The chlorination reaction rate in the pseudo-first-order kinetic model was significantly affected by free available chlorine (FAC) and pH. The increase in pH value led to a decrease in the reaction rate, while a higher dosage of chlorine resulted in a faster kinetic rate. We further estimated the potential toxicities of EZ and its DBPs using quantitative structure-activity relationship (QSAR) software tools. DBPs exhibited much higher toxicity than EZ and exhibited developmental toxicity and mutagenicity. Finally, a total of 108 drinking water samples were collected in the wet and dry seasons to determine actual residue changes in real environmental conditions. The detection frequency was 29% for EZ, and the highest concentration of 0.60 ng L−1 was found for its DBPs in tap water. No seasonal variations in concentration were observed. Overall, the results indicate that EZ and its DBPs may persist in drinking water, posing potential risks to public health.