Clavulanic Acid Decomposition Is Catalyzed by the Compound Itself and by Its Decomposition Products
Abstract
The decomposition kinetics of the beta-lactamase inhibitor clavulanic acid (CA) was investigated for CA concentrations between 2.5 and 20 g L(-1), which is assumed to represent a characteristic range for an industrial CA production process. For each initial concentration, first order kinetics plots could be obtained, however the kinetic constant increased from 3.8 x 10(-3) to 8.6 x 10(-3) h(-1) with increasing initial CA concentration, indicating that CA accelerates its own decomposition by general acid-base catalysis. Furthermore, the kinetic constant remained approximately constant during the reaction, suggesting that also the decomposition products of CA had to show similar catalytic activity. This was confirmed experimentally by increased CA decomposition rates when CA degradation products were added to the reaction. A kinetic model is proposed, which is able to reliably predict the observed pseudo first order rate constants. The presented results should be considered in any process where highly concentrated CA solutions are employed, for example, during final downstream processing or in industrial fermentations.
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β-lactam compounds are susceptible to acid-base catalysis and contain groups such as amino or hydroxyl that can act as catalysts leading to self-catalyzed decomposition.
“The β-lactam compounds are susceptible to acid–base catalysis and contain groups such as amino or hydroxyl, which can act as catalysts leading to a self-catalyzed decomposition [19].”
From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [19]
The trends of CA decomposition in fermentation broth seem to deviate from first and pseudo-first-order kinetics previously reported for CA solutions prepared with standard reactant or commercial formulations.
“The trends of CA decomposition in fermentation broth seem to deviate from first and pseudo-first-order kinetics previously reported for CA solutions prepared with standard reactant or commercial formulations [10,19,23,25,26,27].”
From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [19]
Brethauer et al. proposed a first-order kinetic model in which the kinetic constant increased with increasing initial CA concentration, indicating that CA accelerated its own decomposition.
“A first-order kinetic model was proposed where the kinetic constant increased while increasing the initial CA concentration, indicating that CA accelerated its own decomposition [19].”
From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [19]
Presence of free amino acids and decomposition products in CA solutions increases the degradation rate.
“Presence of free amino acids and decomposition products in CA solutions increase the degradation rate [18,19]; this might be an indicator of susceptibility of CA molecules to nucleophilic attacks added to the variable catalytic effect of pH [10,17,23,25].”
From Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures (2019) · cites this paper as [19]
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Degradation Kinetics of Clavulanic Acid in Fermentation Broths at Low Temperatures
Gómez-Ríos, D., Ramírez-Malule, H., Neubauer, P., Junne, S., & Ríos-Estepa, R. (2019) · Antibiotics · doi:10.3390/antibiotics8010006 · Cited by 17 · see citing works
“A first-order kinetic model was proposed where the kinetic constant increased while increasing the initial CA concentration, indicating that CA accelerated its own decomposition [19].”
BackgroundMethodInfluential
- Authors
- Brethauer, S., Held, M., & Panke, S.
- Affiliations
- ETH Zurich (CH)
- Corresponding author
- Panke, Sven
- Venue
- Journal of Pharmaceutical Sciences
- Publisher
- Elsevier BV
- Published
- 2008-08
- Volume
- 97
- Issue
- 8
- Pages
- 3451-3455
- ISSN
- 0022-3549 (ISSN-L)
- OpenAlex
- W2040145190
- Cited by
- 21
- References
- 0
- Citations by year
- 2026: 1 · 2024: 3 · 2022: 3 · 2021: 2 · 2020: 1 · 2019: 2 · 2018: 1 · 2016: 1 · 2015: 1 · 2013: 2
- FWCI
- 0.54
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Pharmaceutical Sciences (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Physical Sciences › Chemistry › Organic Chemistry › Chemical Reaction Mechanisms
- Physical Sciences › Chemistry › Analytical Chemistry › Analytical Methods in Pharmaceuticals
- Physical Sciences › Materials Science › Materials Chemistry › Thermal and Kinetic Analysis
- Keywords
- clavulanic acid, decomposition kinetics, autocatalysis, general acid-base catalysis, degradation products, pseudo-first-order kinetics, kinetic modeling, beta-lactamase inhibitors, industrial fermentation, downstream processing
- MeSH terms
- Catalysis, Enzyme Inhibitors, Models, Theoretical, Clavulanic Acid, beta-Lactamase Inhibitors
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