目的建立青藤碱、雷公藤甲素皮肤和血液在体微透析方法。方法以青藤碱和雷公藤甲素的回收率(R)为指标,采用增量法考察灌流液体积流量对R的影响,并综合考虑实际操作时需要注意的因素,确定青藤碱和雷公藤甲素微透析的体积流量和取样间隔;采用增量法和减量法考察灌流液质量浓度对探针体外R以及传递率(D)的影响,确定探针R和D之间的比例关系;用在体微透析减量法,考察一定时间间隔内皮肤和血液探针的D,并确定探针R的稳定性。结果增量法中,青藤碱、雷公藤甲素的皮肤和血液探针体外R在0.5~2.5μL/min,随着体积流量的增高而降低,综合考虑到实际实验时间和数据准确性,最后确定体积流量为1μL/min,采样时间间隔为0.5 h;体积流量为1μL/min、青藤碱质量浓度为10~40μg/m L和雷公藤甲素质量浓度为3~12μg/m L时,青藤碱、雷公藤甲素皮肤和血液探针体外R和D稳定且相等,说明药物质量浓度对微透析探针R影响小、在体微透析可以用探针D代替R;在体微透析减量法在10 h内测得的青藤碱和雷公藤甲素皮肤探针体内D分别为(41.27±0.87)%和(37.8±0.99)%,血液微透析探针体内D分别为(44.68±1.28)%和(51.35±1.15)%,说明青藤碱和雷公藤甲素在10 h内探针的D保持稳定。结论建立的青藤碱和雷公藤甲素皮肤与血液微透析方法可用于青藤碱和雷公藤甲素皮肤给药后皮肤和血液药动学研究。 Objective To establish sinomenine and triptolide skin and blood in vivo microdialysis methods. Methods Taking the recoveries of sinomenine and triptolide (R) as indexes, the increment method was used to investigate the effects of volumetric flow rate of perfusate on R, considering the factors needing attention in actual operation, The volume flow rate and sampling interval of etoposide microdialysis were investigated. The effects of concentration of perfusate on the probe R and transmissivity (D) in vitro were investigated by incremental method and decrement method, and the ratio between probes R and D was determined ; In vivo microdialysis reduction method to examine the skin and blood probes D within a certain time interval, and to determine the stability of the probe R. Results Incremental method, sinomenine, triptolide skin and blood probe in vitro R 0.5 ~ 2.5μL / min, with the increase of volume flow rate decreased, taking into account the actual experimental time and data accuracy, Finally, the volume flow rate was 1 μL / min, the sampling time interval was 0.5 h, the volume flow rate was 1 μL / min, the concentration of sinomenine was 10 ~ 40 μg / mL and the triptolide concentration was 3 ~ 12 μg / mL , Sinomenine, triptolide skin and blood probe in vitro R and D stable and equal, indicating that the drug mass concentration on the microdialysis probe R little effect, in vivo microdialysis probe D instead of R; in vivo micro The in vivo D of sinomenine and triptolide probe measured by dialysis and subtraction method in 10 h were (41.27 ± 0.87)% and (37.8 ± 0.99)%, respectively. The in vivo D of blood microdialysis probe was ( 44.68 ± 1.28)% and (51.35 ± 1.15)%, respectively, indicating that the probe D of sinomenine and triptolide remained stable within 10 h. Conclusion The established method of skin and blood microdialysis of sinomenine and triptolide can be used to study skin and blood pharmacokinetics after sinomenine and triptolide skin administration.