FORMATION, ISOLATION AND IDENTIFICATION OF OLIGOMERS OF AZTREONAM

The kinetics of degradation of aztreonam in dilute aqueous solutions has been reported earlier (Pipkin and Barry, 1982; Pipkin, 1986). In dilute aqueous solutions, the major reactions are reported to be the beta-lactam hydrolysis and syn(Z) to anti(E) isomerization of the imino side chain. At higher concentrations (>1% w/v aztreonam), however, the formation of new reaction products was evident. Also, the rate of formation of these degradants increased as a function of the initial aztreonam concentration. A gel permeation chromatography (GPC) method was optimized to isolate these unknown degradants. The isolated GPC fractions were analyzed by mass spectrometrometric analysis, fast atom bombardment (FAB) and by nuclear magnetic resonance (NMR), The fractions were identified as dimeric and trimeric forms of aztreonam.