INTERACTION OF METRONIDAZOLE WITH ANTIBIOTICS CONTAINING THE 2-AMINOTHIAZOLE MOIETY

The mechanism of possible incompatibility between commercially available metronidazole parenteral solutions and the injectable aztreonam leading to the development of pink color in their intravenous admixtures was studied. It was demonstrated that nitrite ions may be produced in metronidazole solutions at the time of preparation or during storage by the effects of temperature and light. Under acidic pH conditions of admixtures the aminothiazole moiety of aztreonam was diazotized by the nitrite ion contributed by metronidazole solutions. The diazotized molecule, in turn, reacted with another aztreonam molecule by diazo-coupling. The resultant pink-colored product was isolated by chromatography and its structure was determined by mass spectral and NMR analyses. Other beta-lactam antibiotics containing the 2-aminothiazole moiety also react in acidic media in a similar manner.