摘要
采用高效液相色谱法(HPLC)和圆二色谱法(CD)考察了p H值、温度、糖类化合物和锌离子等对艾塞那肽溶液稳定性的影响。结果表明,当磷酸盐缓冲液(PBS)p H值为4.0、7.4时,37℃放置10 d时艾塞那肽降解了18%和77%;p H 7.4 PBS于25℃放置10 d时,艾塞那肽降解了33%,4℃放置10 d则无明显降解。添加与药物质量比为1∶1的海藻糖或蔗糖、或添加低浓度锌离子可使艾塞那肽溶液的热变性温度从72.8℃分别提高至94.9、83.0和85.0℃。本研究表明p H值偏中性或温度升高,会使艾塞那肽稳定性降低,而添加海藻糖、蔗糖或锌离子可提高其稳定性。
An HPLC method and a circular dichroism spectroscopy were adopted to investigate the effects of pH values, temperatures, carbohydrate polymers and Zn^2＋ on the stability of exenatide solution. The results showed that exenatide degraded in phosphate buffer （PBS） at 37 ℃ for 10 d, and the drug content decreased by 18% at pH 4.0 and 77% at pH 7.4. In pH 7.4 PBS stored at 25 ℃ for 10 d, the exenatide content decreased by 33%, whereas there was no obvious degradation of exenatide observed in PBS stored at 4 ℃ for 10 d. When adding trehalose or sucrose with exenatide in a 1 ： 1 ratio, or adding Zn^2＋ with lower concentration, the thermal denaturation temperature of exenatide increased from 72.8 ℃ to 94.9, 83.0 or 85.0 ℃. These results indicated that near-neutral pH environment or high temperature was destructive to the stability of exenatide, while adding trehalose, sucrose or Zn^2＋ could improve the stability.
出处
《中国医药工业杂志》
CAS
CSCD
北大核心
2016年第6期711-716,共6页
Chinese Journal of Pharmaceuticals
关键词
艾塞那肽
稳定性
高效液相色谱法
圆二色谱
热变性温度
exenatide
stability
HPLC
circular dichroism spectroscopy
thermal denaturation temperature
