Transformation of levofloxacin during water chlorination process: kinetics and pathways

Abstract

The kinetics and mechanism of removal of the fluoroquinolone antibacterial levofloxacin (LFC) by free available chlorine (FAC) during water chlorination processes have been investigated for the first time between pH values 4.2 and 8.5. The pH-dependent second-order rate constants were found to decrease with increase in pH (e.g. apparent second order rate constant; k00 app ¼ 20 dm3 mol 1 s 1 at pH 4.2 and k00 app ¼ 1dm3 mol 1 s 1 at pH 8.5 and at 25 C). The products of the reaction were determined by liquid chromatography and high resolution mass spectrometry. There are two plausible pathways for the LFC chlorination. The major channel is electrophilic halodecarboxylation of the quinolone moiety in which HOCl reacts at tertiary N(4) amine to form a reactive chlorammonium intermediate (R3N(4)Clþ) that can catalytically halogenate LFC, and the minor channel is chlorination at the piperazinyl moiety in which HOCl reacts at tertiary N(4) amine to form a reactive chlorammonium intermediate (R3N(4)Clþ) followed by intermediate degradation both at the piperazinyl and quinolone moieties with successive chlorination. The effect of temperature on the rate of the reaction was studied at four different temperatures and rate constants were found to increase with increase in temperature and the thermodynamic activation parameters Ea, DH6¼, DS6¼ and DG6¼ were evaluated and discussed.