目的:研究一种青藤碱雷公藤甲素巴布剂裸鼠透皮吸收过程。方法:采用微透析联用HPLC的方法,以30%乙醇/生理盐水为灌流液,样品以Diamonsil-C18(4.6 mm×250 mm,5μm)为色谱柱,以甲醇-磷酸盐缓冲液(pH 9.0)(55∶45)为流动相,检测波长为225 nm的条件下进行分析,经过反透析法体内回收率校正后,所得的裸鼠皮下游离青藤碱雷公藤甲素浓度采用WINNONLIN 5.2程序以非房室模型方法计算药代动力学参数。结果:青藤碱达峰时间为14 h,达峰浓度为30.15μg.mL-1。雷公藤甲素达峰时间为10 h,达峰浓度为3.31μg.mL-1。结论:本方法能够在体、实时监测裸鼠皮下青藤碱雷公藤甲素的动态浓度,为局部药动学研究提供新的方法学参考。
Objective: To determine the concentration of sinomenine and triptolide in nude mouse hypodermis.Method: Microdialysis coupled with high-performance liquid chromatography was developed for on-line determination of the in vivo concentration of sample,when the perfusate was 30% ethanol /physiological saline solution.The Diamonsil-C18 column(4.6 mm × 250 mm,5 μm) was used and the mobile phase consisted of methanol∶ buffer phosphate(pH 9.0)(55∶ 45).The detect wave length was 225 nm.The data obtained after being calculated using the relative recovery in vivo were dealed with WINNONLIN 5.2 programe,while retro-dialysis method was used to study relative recovery in vivo.Result:The peak time of sinomenine and triptolide were 14 h and 10 h,peak concentrations were 30.15 μg.mL-1 and 3.31 μg.mL-1 respectively.Conclusion:The method can be used to determine in vivo and real time concentration of sinomenine and triptolide in the skin dynamically.It is suitable for the pharmacokinetics study of sinomenine and triptolide at the same time.