Ito Nobuya, Suzuki Masahiko, Kusai Akira, Takayama Kozo
Pharmaceutical Development Laboratories, SANKYO CO., LTD, Hiratsuka-shi, Kanagawa, Japan.
Chem Pharm Bull (Tokyo). 2005 Mar;53(3):323-7. doi: 10.1248/cpb.53.323.
The effect of initial panipenem (CAS No. 87726-17-8) concentration on its degradation in an aqueous solution was investigated. The degradation of panipenem followed pseudo-first-order kinetics at all the pH values tested. However, in an acidic solution, the degradation rate increased with the initial panipenem concentration. On the other hand, in an alkaline solution, the degradation rate was not affected by its initial concentration. In an acidic solution, the plots of the first-order rate constants versus initial panipenem concentrations showed a linear relationship. Theoretically, the first-order rate constant is independent of the initial concentration, and therefore, the results suggested unusualness. We investigated the results obtained under acidic conditions in detail to find a very complex reaction mechanism: panipenem and its degradation products are factors causing the unusual increase in the degradation rate. Moreover, it was shown that the dissociation of the carboxyl group played an important role in the degradation of panipenem.
研究了初始帕尼培南(化学物质登记号:87726 - 17 - 8)浓度对其在水溶液中降解的影响。在所有测试的pH值条件下,帕尼培南的降解均遵循准一级动力学。然而,在酸性溶液中,降解速率随初始帕尼培南浓度的增加而增大。另一方面,在碱性溶液中,降解速率不受其初始浓度的影响。在酸性溶液中,一级速率常数与初始帕尼培南浓度的关系图呈现出线性关系。从理论上讲,一级速率常数与初始浓度无关,因此,这些结果表明存在异常情况。我们详细研究了在酸性条件下获得的结果,以发现一个非常复杂的反应机制:帕尼培南及其降解产物是导致降解速率异常增加的因素。此外,结果表明羧基的解离在帕尼培南的降解过程中起着重要作用。