title: Studies on orally active cephalosporin esters. II. Chemical stability of pivaloyloxymethyl esters in phosphate buffer solution.
abstract: The degradation kinetics of pivaloyloxymethyl (POM) esters of cephalosporins in phosphate buffer solution (pH 6-8) were investigated. The degradation of the starting delta 3 cephalosporin ester proceeded mainly via isomerization to the delta 2 ester and subsequent hydrolysis to the delta 2 acid. Hydrolysis to the delta 3 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 delta 3 ester kdeg, and slower than the hydrolysis rate of the delta 2 ester k24. The isomerization process to the delta 2 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 concentration and added protein.
authors.forename: M
authors.initials: M
authors.lastname: Miyauchi
authors.forename: K
authors.initials: K
authors.lastname: Sasahara
authors.forename: K
authors.initials: K
authors.lastname: Fujimoto
authors.forename: I
authors.initials: I
authors.lastname: Kawamoto
authors.forename: J
authors.initials: J
authors.lastname: Ide
authors.forename: H
authors.initials: H
authors.lastname: Nakao
mesh_terms: D000284:Administration, Oral; D002021:Buffers; D002511:Cephalosporins / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics*; D055598:Chemical Phenomena; D002621:Chemistry; D004355:Drug Stability; D004952:Esters; D010421:Pentanoic Acids / Q000008:administration & dosage / Q000138:chemical synthesis / Q000493:pharmacokinetics; D010710:Phosphates
chemical_list: D002021:Buffers; D002511:Cephalosporins; D004952:Esters; D010421:Pentanoic Acids; D010710:Phosphates