Degradation kinetics and formation of regulated and emerging disinfection by-products during chlorination of two expectorants ambroxol and bromhexine

Ambroxol hydrochloride (AMB) and bromhexine hydrochloride (BRO) are classic expectorants and bronchose-cretolytic pharmaceuticals. In 2022, both AMB and BRO were recommended by medical emergency department of China to alleviate cough and expectoration for symptoms caused by COVID-19. The reaction characteristics and mechanism of AMB/BRO with chlorine disinfectant in the disinfection process were investigated in this study. The reaction of chlorine with AMB/BRO were well described by a second-order kinetics model, first-order in both AMB/BRO and chlorine. The second order rate reaction constant of AMB and BRO with chlorine at pH 7.0 were 1.15 x 102 M - 1s- 1and 2.03 x 102 M - 1s- 1,respectively. During chlorination, a new class of aromatic nitrogenous disinfection by-products (DBPs) including 2-chloro-4, 6-dibromoaniline and 2, 4, 6-tribromoaniline were identified as the intermediate aromatic DBPs by gas chromatography-mass spectrometry. The effect of chlorine dosage, pH, and contact time on the formation of 2-chloro-4, 6-dibromoaniline and 2, 4, 6-tribromoani-line were evaluated. In addition, it was found that bromine in AMB/BRO were vital bromine source to greatly promote the formation of classic brominated DBPs, with the highest Br-THMs yields of 23.8% and 37.8%, respectively. This study inspired that bromine in brominated organic compounds may be an important bromine source of brominated DBPs.