Identification, Mechanisms and Kinetics of Macrolide Degradation Product Formation under Controlled Environmental Conditions

Abstract

Erythromycin, azithromycin, clarithromycin and roxithromycin are antibiotics belonging to the widely used macrolide group. Their presence in the environment has been much investigated, despite the rapid degradation of Erythromycin to its spiroketal degradation product. In this study, the formation of macrolide degradation products was investigated in various aqueous solutions, each containing 100 μg/mL of the respective macrolide, under controlled artificial conditions: three phosphate buffer solutions (pH 5, pH 7 and pH 8.5), and a buffer solution at pH 7 with the addition of humic acids. Two solutions from natural sources were also examined: secondary effluent and tap water. The obtained degradation products were identified by their HRMS and NMR spectra (for Erythromycin-spiroketal, obtained from pure compounds isolated by preparative HPLC) as: N-oxide, N-desmethyl and N-didesmethyl forms of all examined macrolides. These degradation products were obtained only under irradiation by sunlight, while the Erythromycin-H2O degradation products were also obtained in the shade. The secondary effluent was the most significant medium for achieving macrolide degradation products. According the degradation product’s t1/2 values obtained in the secondary effluent, the azithromycin was most rapidly degraded (23 hours). Furthermore, results suggested that the degradation process was activated by sunlight irradiation energy, and that the degradation mechanism started with the transfer of an electron from the amine group to O2 to produce the radical ions RMe2N·+ and O2 ·- as intermediates and production of the N-oxide and N-desmethyl macrolide degradation products. The kinetics of macrolide degradation was calculated as a first-order reaction.