FORMATION, ISOLATION AND IDENTIFICATION OF OLIGOMERS OF AZTREONAM

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