除虫脲在人工胃/肠液和肠道菌群及生物样品中的稳定性研究

为了考察除虫脲(DFB)在人工胃/肠液和肠道菌群及生物样品中的稳定性,为合理开发DFB口服制剂提供试验依据。采用高效液相色谱法(HPLC),分别将DFB与空白人工胃液(pH为1.3,不含酶)、空白人工肠液(pH为6.8,不含酶)、人工胃液(pH为1.3,含胃蛋白酶)、人工肠液(pH为6.8,含胰蛋白酶)、SD大鼠(雄性)肠道菌群或生物样品分别共孵育不同时间后,检测DFB的含量变化。结果表明,DFB在空白人工胃液和人工胃液中孵育0～2 h剩余百分比基本没有发生变化,之后随着时间的增加,剩余百分比略有下降,但剩余百分比都在90%以上,总体呈现稳定趋势。在空白人工肠液中孵育,剩余百分比随着时间增加显著下降,孵育6 h后剩余百分比为82.97%;在人工肠液中孵育6 h, DFB的剩余百分比为77.41%。DFB在SD大鼠肠道菌群中孵育12 h发生部分降解,但DFB的剩余百分比在90%以上,总体呈稳定趋势。DFB在肝、胃、大肠等生物样品中孵育6 h后,DFB的剩余百分比均在90%以上;而在小肠生物样品中孵育6 h后DFB的剩余百分比为84.06%。

Stability of Diflubenzuron in Artificial Stomach and Intestinal Fluid,Intestinal Flora and Biological Samples

To provide a theoretical basis for diflubenzuron (DFB) in the development of oral preparations,the stability of DFB in the artificial stomach/intestinal fluid,intestinal flora,and biological samples were investigated.High performance liquid chromatography (HPLC) was used to determine the contents of DFB which incubated in blank artificial gastric fluid (pH=1.3,without enzyme),blank artificial intestinal fluid (pH=6.8,without enzyme),artificial gastric fluid (pH=1.3,with pepsin),artificial intestinal fluid (pH=6.8,with trypsin),intestinal flora and biological samples of SD rats for different incubation times.The content variation of DFB was calculated.The results showed that the remaining percentage of DFB in blank artificial gastric juice and artificial gastric juice did not change after 0-2 h incubation,and the remaining percentage declined marginally with the increase of incubation time,but the remaining percentage was more than 90 percent.When DFB were incubated in blank artificial intestinal fluid and artificial intestinal fluid,the remaining percentages decreased significantly with time,and the remaining percentage were 82.97% and 77.41%,respectively.DFB was partially degraded in the intestinal flora of SD rats after 12 hours incubation,but the residual percentage of DFB was more than 90%.The residual percentages of DFB were more than 90% when DFB were incubated with the homogenates of rat liver,stomach,large intestine for 6 hours,while the residual percentage of DFB was 84.06% after 6 hours incubation with small intestinal biological products.