Faculty of Pharmacy in Hradec Králové, Department of Pharmaceutical Chemistry and Pharmaceutical Analysis, Charles University in Prague, Heyrovského 1203, 500 05, Hradec Králové, Czech Republic.
Environ Sci Pollut Res Int. 2017 Oct;24(29):23196-23206. doi: 10.1007/s11356-017-9743-5. Epub 2017 Aug 22.
Over the past decade, the environment has been polluted by a wide spectrum of exogenous chemicals and environmental analysis has become one of the most progressive parts of analytical research. The aim of this work was to determine the kinetics of natural degradation, and to identify the degradation products of the massively used estrogenic drug, 17-α-ethinylestradiol. The photodegradation, oxidation and thermostability conditions were selected according to ICH requirements for pharmaceutical stability testing. A simple 72-h photodegradation study in purified water exhibited significant first-order kinetics with the kinetic constant k = 0.0303 h, and degradation halftime 22.8 h. The basic halftime could be reduced to 17.1 h by the addition of sea salt, and increase in temperature. Monohydroxy, dihydroxy and dehydrogenated derivatives of ethinylestradiol with intact steroidal structure were identified as major degradation products resulting from simple photodegradation. The addition of an oxidative agent significantly accelerated the degradation rate; combined with higher temperature, the degradation halftime was reduced to 1.1 h with the first-order kinetic constant k = 0.632 h. TOC analysis showed a notable decrease of organic mass (18% in 3 days) during oxidation experiments, and confirmed the degradation of steroidal structure.
在过去的十年中，环境受到了广泛的外源化学物质的污染，环境分析已成为分析研究中最先进的领域之一。本工作旨在确定天然降解的动力学，并鉴定大量使用的雌激素药物 17-α-乙炔基雌二醇的降解产物。根据 ICH 对药物稳定性测试的要求，选择了光降解、氧化和热稳定性条件。在纯净水中进行的简单 72 小时光降解研究表明，具有显著的一级动力学，动力学常数 k=0.0303 h，半衰期 22.8 h。通过添加海盐和升高温度，基本半衰期可缩短至 17.1 h。从简单的光降解中鉴定出作为主要降解产物的炔雌醇的单羟基、二羟基和脱氢衍生物，其甾体结构保持完整。添加氧化剂可显著加速降解速率；与较高温度结合，一级动力学常数 k=0.632 h 时，半衰期缩短至 1.1 h。TOC 分析表明，在氧化实验过程中有机质量明显下降（3 天内下降 18%），并证实了甾体结构的降解。
