Levofloxacin ozonation in water: Rate determining process parameters and reaction pathway elucidation

Ozonation of the quinolone antibiotic levofloxacin was investigated with focus on both the levofloxacin degradation rate and degradation product formation. Degradation was about 2 times faster at pH 10 compared to pH 3 and 7 explained by direct ozonation at the unprotonated N4′, one of the tertiary amines of the piperazinyl substituent. H2O2 concentration (2-100 μM) had only limited effect. Liquid chromatography - high resolution mass spectrometry revealed degradation at the piperazinyl substituent and the quinolone moiety, with the relative importance of both pathways being strongly affected by changes in pH. Levofloxacin N-oxide concentrations reached up to 40% of the initial levofloxacin concentration during ozonation at pH 10. Degradation at the quinolone moiety resulted in isatin and anthranilic acid type metabolites, probably formed through reaction with hydroxyl radicals. Ab initio molecular orbital calculations predicted radical attack mainly at C2 of the quinolone moiety. This is the carbon atom with the largest Fukui function. Reaction with ozone is expected to mainly occur at N4′, characterized by the largest negative charge.