Stability in aqueous solution of two monocyclic beta-lactam antibiotics: aztreonam and nocardicin A.
The catalytic effect of various buffer systems (citrates, acetates, phosphates, borates and carbonates) on the degradation of aztreonam and nocardicin A in aqueous solution was studied at 35 degrees C and a constant ionic strength of 0.5 mol.dm-3 over a pH range of 3.50 to 10.50. The observed degradation rates, obtained by measuring the remaining intact antibiotic, were shown to follow pseudo-first-order kinetics with regard to antibiotic concentrations and to be influenced by general acid and general base catalysis. The changes in the concentration of intact beta-lactam antibiotic in the solutions were established by reverse-phase HPLC with UV-detection. In general the buffer systems employed in the kinetic studies showed a very weak catalytic effect on the degradation of aztreonam and nocardicin A. The pH-rate profiles for these antibiotics showed degradation minimums at pH 5.38 and 6.13, respectively. Aztreonam is slightly more reactive with hydrogen ions than nocardicin A and is much more reactive with hydroxide ions. In comparison with other beta-lactamic antibiotics, aztreonam and nocardicin A are much more stable in aqueous solution, except for aztreonam in a base solution, which is just as unstable as penicillins and cephalosporins. The Arrhenius activation energies were determined for aztreonam and nocardicin A at pH's 4.23, 6.59 and 8.60.
Méndez
R
R
Departamento de Bioquímica y Biología Molecular, Facultades de Biología y Veterinaria, Universidada de León, Spain.
Alemany
T
T
Martín-Villacorta
J
J
D000900:Anti-Bacterial Agents / Q000737:chemistry* / Q000493:pharmacokinetics; D001398:Aztreonam / Q000737:chemistry* / Q000493:pharmacokinetics; D002021:Buffers; D002384:Catalysis; D004355:Drug Stability; D006863:Hydrogen-Ion Concentration; D007700:Kinetics; D007769:Lactams; D012996:Solutions; D013329:Structure-Activity Relationship; D013696:Temperature; D047090:beta-Lactams
D000900:Anti-Bacterial Agents; D002021:Buffers; D007769:Lactams; D012996:Solutions; D047090:beta-Lactams; C027318:nocardicin; D001398:Aztreonam