苦参碱微乳经皮给药在小鼠体内的药动学及组织分布研究

 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。

Pharmacokinetics and Distribution of Microemulsion System for Transdermal Delivery of Matrine in Mouse

ABSTRACT OBJECTIVE To develop a highly sensitive， simple and selective gas-chromatography mass spectrometry (GC/MS) method for investigating the pharmacokinetics and distribution of matrine in mouse plasma， and tissues respectively. METHODS The contents of matrine in mouse plasma and tissues were determined using GC/MS. The pharmacokinetic parameters were calculated by DAS 2.0.RESULTS The linearity was ranged from 32 to 800 ng·mL-1(r=0.999 5). The RSDs(%) of within-day and between-day were all below 2.8%. The absolute recovery was in the range of 72.2%-78.8%. The method recovery was 92.1%-98.9%. The matrine-loaded microemulsion built up more stable and persistent drug level than matrine injection（P＜0.01）. After percutaneous administration of matrine-loaded microemulsion， the sequence of contents of matrine in tissues was as follows: lung＞kidney＞spleen＞liver＞heart. CONCLUSION The GC/MS method was successfully applied to quantify the low matrine concentration in plasma samples and tissues， and suitable for its pharmacokinetic studies. The matrine-loaded microemulsion presented a permeation model with zero-order kinetics. Furthermore， the matrine-loaded microemulsion can build up a higher，more stable and persistent blood drug level than that of matrine injection. It have a good prospect of exploitation and utilization.