Tsuji A, Miyamoto E, Terasaki T, Yamana T
J Pharm Sci. 1979 Oct;68(10):1259-63. doi: 10.1002/jps.2600681017.
Both ester and beta-lactam degradations of alpha-esters of carbenicillin disodium, carbenicillin indanyl sodium, and carbenicillin phenyl sodium in aqueous solution at 35 degrees and at 0.5 ionic strength were investigated. The reactions were followed by spectrophotometric assay, reversed-phase high-pressure liquid chromatography, and colorimetric assay. The degradation pathways were established, and the rate-pH profiles for ester and beta-lactam cleavage reactions are given for pH 1-11. Below pH 3, the beta-lactam degradation of the prodrugs proceeded exclusively. Above pH 7, the degradation was superseded by the ester hydrolysis to carbenicillin, beta-Lactams of both prodrugs are around three times more stable than carbenicillin disodium at pH 1, six times at PH 2, and 17 times at pH 3. The half-lives for carbenicillin production were predicted to be 17 hr for carbenicillin indanyl sodium and 8.5 hr for carbenicillin phenyl sodium at pH 7.0 and 37 degrees.
研究了羧苄西林二钠、羧苄西林茚满酯钠和羧苄西林苯酯钠的α-酯在35℃、离子强度为0.5的水溶液中的酯降解和β-内酰胺降解情况。通过分光光度法测定、反相高效液相色谱法和比色法测定跟踪反应。确定了降解途径，并给出了pH值为1 - 11时酯和β-内酰胺裂解反应的速率 - pH曲线。在pH值低于3时，前药的β-内酰胺降解占主导。在pH值高于7时，酯水解生成羧苄西林取代了降解反应。两种前药的β-内酰胺在pH值为1时比羧苄西林二钠稳定约3倍，在pH值为2时稳定6倍，在pH值为3时稳定17倍。在pH值为7.0和37℃时，羧苄西林茚满酯钠生成羧苄西林的半衰期预计为17小时，羧苄西林苯酯钠为8.5小时。
