地西泮直肠溶液有关物质的HPLC测定方法及稳定性初步研究

HPLC method for the determination of related substances and stability study of diazepam rectal solution

目的建立高效液相色谱法(HPLC)测定地西泮直肠溶液中有关物质,并考察不同影响因素下有关物质含量的变化。方法系统验证有关物质方法学,分别考察专属性、重复性、准确度、稳定性与方法耐用性等,并以此法研究地西泮直肠溶液在不同条件下的有关物质变化。结果该法的检测限为15 ng/ml,定量限40 ng/ml,重复性RSD为0.04%,平均回收率为(99.52±0.38)%;地西泮直肠溶液在光照和60℃条件下有关物质显著增加,并伴有颜色改变。结论该法简单可行,稳定可靠,可用于地西泮直肠溶液的有关物质研究;该制剂在光照与高温下会产生较多杂质,应在避光室温条件下保存。

Objective To develop a HPLC method for the determination of related substances in rectal solution of diazepam and the changes in the content of related substances under different conditions. Methods The specificity,linearity,reproducibility,accuracy,stability,and durability of the HPLC method were examined systematically;and the method was used to study changes in related substances of diazepam rectal solution under different conditions. Results The specificity,reproducibility,precision,stability and durability of the method were good. The detection limit of the method was 15 ng/ml,the quantitative limit was 40 ng/ml,the RSD of reproducibility was 0.04%,and the average recovery was(99.52±0.38)%(n=9). The related substances in diazepam rectal solution significantly increased under light and at 60℃,with color changes. Conclusion The method is simple,feasible,stable and reliable,which could be used for research on related substances in rectal solution of diazepam. However,the preparation can produce more impurities under the light and high temperature,and therefore should be stored in light-avoiding room temperature conditions.