苯巴比妥钠注射液的分解产物

苯巴比妥系缩丙二酰脲衍生物。由于结构中脲与酰基相接的氮原子既与酰基产生P-π共轭,又与脲中羰基产生P-π共轭,分散了该氮原子上的P电子云密度,从而使酰脲的给电子共轭效应减少,酰基上的碳原子易受羟基的攻击开环水解,继而脱去CO_2生成主要分解产物苯乙基醋酰脲。其加水分解反应历程如下。     

10%苯巴比妥钠注射液贮存期预测

The shelf-life of 10% sodium phenobarbital injection(containing propylene glycol 60%) has been predicted by accelerated stability test with the classical isothermal method (at 100, 90, 80 and 70℃). The data was treated with regressive calculation, and the shelf-life calculated with three different methods (regressive calculation, average activation energy calculation and graphical plotting).The values obtained from these three methods were approximately equal, and also coincided with the value obtained from samples reserved for observation at room temperature. The shelf-life was 1.05 years at 25℃, and 2.03 years at 20℃.     

苯巴比妥钠注射液的稳定化

前两报研究证明,苯巴比妥钠注射液稳定性较差,贮存期短。根据化学动力学研究,降低溶液的pH值可明显增加其稳定性。但经我们计算,25℃时10％的苯巴比妥钠水溶液当pH值降至9.18时即析出苯巴比妥沉淀。显然,通过降低pH值的途径使其稳定受到限制。     

10%苯巴比妥钠注射液贮存期预测

苯巴比妥钠系缩丙二酰脲衍生物,不稳定易加水分解。关于苯巴比妥的水解动力学和稳定性研究报道较多,但对10％苯巴比妥钠丙二醇(60％)注射液的贮存期预测,未见报道。作者根据Arrhenius定律用恒温加速试验法,然后外推至室温预测贮存期。并用回归方程处理实验数据。     

苯巴比妥钠注射液的分解产物

A major degradated product was obtained from sodium phenobarbital injection stored at room temperature or heated at 100℃ for a long time. It was identified by means of melting point, optical rotation, UV and IR spectrum, elemental analysis and paper chromatography to be dl-pheneturide irrespective of the source of sample.A search in the literature showed that this degradated product is a potent anticonvulsant.