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

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The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH6-8) were investigated. The degradation of the starting &Delta;<SUP>3</SUP> cephalosporin ester proceeded mainly via isomerization to the &Delta;<SUP>2</SUP> ester and subsequent hydrolysis to the &Delta;<SUP>2</SUP> acid. Hydrolysis to the &Delta;<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 &Delta;<SUP>3</SUP> ester k<SUB>deg</SUB>, and slower than the hydrolysis rate of the &Delta;<SUP>2</SUP> ester k<SUB>24</SUB>. The isomerization process to the &Delta;<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.