Kinetics and Mechanism of Decomposition of Cefazolin Ester in Phosphate Buffer Solution

Abstract

We evaluated the rate and mechanism of decomposition of cefazolin methyl ester (Δ³ ester) in phosphate buffer (pH 8.4).The decomposition of Δ³ ester proceeded simultaneously via 3 pathways. The first pathway is production of Δ² ester (rate k₁₂) by isomerization and production of Δ² acid (k₂₃) by hydrolysis of the Δ₂ ester. The second pathway is the cleavage reaction of the β-lactam ring and simultaneous elimination of the substituent at position 3 (k₁₄). The third pathway is production of Δ³ acid (k₁₅) by hydrolysis of the carboxylic ester at position 4.Kinetic analysis of each pathway was performed. The reaction rate constant from Δ² ester to Δ² acid (k₂₃) was the highest, and the reaction rate constant for the production of Δ² ester by isomerization (k₁₂) was similar to that for the elimination of the position 3 substituent by cleavage of the β-lactam ring (k₁₄). The rate of production of Δ³ acid by hydrolysis of the position 4 carboxylic ester was the lowest.These results show that Δ³ ester decomposition under a basic condition predominantly occurs through cleavage reaction of the β-lactam ring and Δ² ester producion by isomerization.Since the production of Δ² acid markedly depended on the production of Δ² ester by isomerization, Δ² ester production is the rate-limiting step of this pathway.