Stability and kinetics of degradation of imipenem in aqueous solution

In weakly acidic solution, the broad-spectrum antibiotic imipenem undergoes complex oligomerization initiated by intermolecular carboxyl group attack on the beta-lactam group. In weakly alkaline solution, intermolecular reaction between the beta-lactam and formimidoyl groups occurs instead. Both bet...

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Bibliographic Details
Published inJournal of pharmaceutical sciences Vol. 79; no. 8; p. 732
Main Authors Smith, G B, Dezeny, G C, Douglas, A W
Format Journal Article
LanguageEnglish
Published United States 01.08.1990
Subjects
Catalysis
Chemical Phenomena
Chemistry
Chromatography, High Pressure Liquid
Drug Stability
Hydrogen-Ion Concentration
Imipenem - analysis
Kinetics
Magnetic Resonance Spectroscopy
Models, Chemical
Spectrophotometry, Ultraviolet
Temperature
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Summary:In weakly acidic solution, the broad-spectrum antibiotic imipenem undergoes complex oligomerization initiated by intermolecular carboxyl group attack on the beta-lactam group. In weakly alkaline solution, intermolecular reaction between the beta-lactam and formimidoyl groups occurs instead. Both beta-lactam and formimidoyl groups also hydrolyze at pH-dependent rates. Complex decomposition schemes were determined in kinetic studies at pH 4.0 and 9.0-9.5 using HPLC and mathematical models. The rates of the several initial reactions, calculated as functions of pH and imipenem concentration by fitting the models to kinetic data, fully account for imipenem decomposition rates throughout the neutral pH range.
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.2600790816