- 著者
- 宮内 正雄 笹原 邦宏 藤本 光一 川本 勲 井手 純也 中尾 英雄
- 出版者
- The Pharmaceutical Society of Japan
- 雑誌
- Chemical and Pharmaceutical Bulletin (ISSN:00092363)
- 巻号頁・発行日
- vol.37, no.9, pp.2369-2374, 1989-09-25 (Released:2008-03-31)
- 参考文献数
- 21
- 被引用文献数
- 10 9
The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ3 cephalosporin ester proceeded mainly via isomerization to the Δ2 ester and subsequent hydrolysis to the Δ2 acid. Hydrolysis to the Δ3 acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k12 was approximately equal to the apparent degradation rate of the Δ3 ester kdeg, and slower than the hydrolysis rate of the Δ2 ester k24. The isomerization process to the Δ2 ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.
- 著者
- 宮内 正雄 笹原 邦宏 藤本 光一 川本 勲 井手 純也 中尾 英雄
- 出版者
- 公益社団法人 日本薬学会
- 雑誌
- CHEMICAL & PHARMACEUTICAL BULLETIN (ISSN:00092363)
- 巻号頁・発行日
- vol.37, no.9, pp.2369-2374, 1989
- 被引用文献数
- 9
The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting Δ<SUP>3</SUP> cephalosporin ester proceeded mainly via isomerization to the Δ<SUP>2</SUP> ester and subsequent hydrolysis to the Δ<SUP>2</SUP> acid. Hydrolysis to the Δ<SUP>3</SUP> acid (the parent acid) was very slow. Analysis of the rate constants indicated that the isomerization rate k<SUB>12</SUB> was approximately equal to the apparent degradation rate of the Δ<SUP>3</SUP> ester k<SUB>deg</SUB>, and slower than the hydrolysis rate of the Δ<SUP>2</SUP> ester k<SUB>24</SUB>. The isomerization process to the Δ<SUP>2</SUP> ester was found to be the rate-determining step in the degradation of cephalosporin esters. The substituent at the C-3 position of the cephalosporins affected the degradation kinetics. The degradation was accelerated by increase of pH, buffer concentartion and added protein.