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

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We evaluated the rate and mechanism of decomposition of cefazolin methyl ester (Δ^3 ester) in phosphate buffer (pH 8.4).The decomposition of Δ^3 ester proceeded simultaneously via 3 pathways. The first pathway is production of Δ^2 ester (rate k_<12>) by isomerization and production of Δ^2 acid (k_<23>) by hydrolysis of the Δ_2 ester. The second pathway is the cleavage reaction of the β-lactam ring and simultaneous elimination of the substituent at position 3 (k_<14>). The third pathway is production of Δ^3 acid (k_<15>) by hydrolysis of the carboxylic ester at position 4.Kinetic analysis of each pathway was performed. The reaction rate constant from Δ^2 ester to Δ^2 acid (k_<23>) was the highest, and the reaction rate constant for the production of Δ^2 ester by isomerization (k_<12>) was similar to that for the elimination of the position 3 substituent by cleavage of the β-lactam ring (k_<14>). The rate of production of Δ^3 acid by hydrolysis of the position 4 carboxylic ester was the lowest.These results show that Δ^3 ester decomposition under a basic condition predominantly occurs through cleavage reaction of the β-lactam ring and Δ^2 ester producion by isomerization.Since the production of Δ^2 acid markedly depended on the production of Δ^2 ester by isomerization, Δ^2 ester production is the rate-limiting step of this pathway.
公益社団法人日本薬学会の論文
1996-03-15