目的建立小鼠血浆苦参碱的GC-MS联用分析法,测定药动学参数和组织分布。方法小鼠分别腹腔注射苦参碱注射液和经皮给苦参碱微乳,用GC-MS分析法分别测定血浆和各组织中苦参碱浓度,计算药动学参数和组织中苦参碱含量。结果苦参碱在32~800 ng.mL-1内线性关系良好(r=0.999 5),最低检出限量1 ng.mL-1,日间和日内RSD均小于2.8%,提取回收率为72.2%~78.8%,方法回收率为92.1%~98.9%。苦参碱微乳经皮给药比苦参碱注射液腹腔注射,血药浓度稳定持久,具有显著差异(P<0.01);苦参碱微乳经皮给药后,在组织中的分布由高到低依次是肺、肾、脾、肝和心。结论本方法专属性、准确度、灵敏性高;微乳中苦参碱以零级动力学透过皮肤,可提供比注射剂更为稳定的血药浓度,具有开发应用前景。 Objective To establish a mouse GC-MS analysis of plasma matrine and determine the pharmacokinetic parameters and tissue distribution. Methods Mice were injected intraperitoneally with matrine and matrine microemulsion. The concentrations of matrine in plasma and tissues were determined by GC-MS. The pharmacokinetic parameters and matrine content. Results Matrine had a good linearity (r = 0.999 5) within 32 800 ng · mL-1 and a minimum detectable limit of 1 ng.mL-1 with RSD less than 2.8% during day and day and recovery of 72.2 % ~ 78.8%, the recovery rate was 92.1% ~ 98.9%. Matrine microemulsion percutaneous administration of intraperitoneal injection of matrine than the injection of plasma concentration was stable and lasting, with significant differences (P <0.01); matrine microemulsion after transdermal administration, the distribution in the tissue from High to low followed by lung, kidney, spleen, liver and heart. Conclusion The specificity, accuracy and sensitivity of the method are high. Matrine in the microemulsion permeates the skin with zero-order kinetics and can provide more stable blood concentration than the injection, which has the prospect of development and application.