Kinetics and mechanism of decomposition of cefazolin ester in phosphate buffer solution

Article abstract of DOI:10.1248/cpb.44.599

We evaluated the rate and mechanism of decomposition of cefazolin methyl ester (Λ³ ester) in phosphate buffer (pH 8.4). The decomposition of Λ³ ester proceeded simultaneously via 3 pathways. The first pathway is production of Λ² ester (rate k₁₂) by isomerization and production of Λ² acid (k₂₃) by hydrolysis of the Λ² 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 Λ³ acid (k₁₅) by hydrolysis of the carboxylic ester at position 4. Kinetic analysis of each pathway was performed. The reaction rate constant from Λ² ester to Λ² acid (k₂₃) was the highest, and the reaction rate constant for the production of Λ² 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 Λ³ acid by hydrolysis of the position 4 carboxylic ester was the lowest. These results show that Λ³ ester decomposition under a basic condition predominantly occurs through cleavage reaction of the β-lactam ring and Λ² ester production by isomerization. Since the production of Λ² acid markedly depended on the production of Λ² ester by isomerization, Λ² ester production is the rate- limiting step of this pathway.

Full text of DOI:10.1248/cpb.44.599

NII-Electronic Library Service

NII-Electronic Library Service

NII-Electronic Library Service