目的 考察延胡索和白芷配伍对延胡索甲素、延胡索乙素、原阿片碱、欧前胡素及异欧前胡素在大鼠脑组织内分布动力学的影响，为元胡止痛方中质量标志物（Q-marker）的确定提供进一步的实验依据。方法 分别ig给予大鼠延胡索、白芷及元胡止痛方提取物，采用UPLC-MS/MS测定不同时间点大鼠脑组织样品中各成分的质量浓度，拟合动力学参数评价组方配伍对各成分在大鼠脑组织中分布的影响。结果 与延胡索、白芷组相比，元胡止痛方组大鼠脑组织中延胡索甲素、延胡索乙素和原阿片碱的达峰浓度（C_max）和药时曲线下面积（AUC）均显著增加，欧前胡素、异欧前胡素平均驻留时间（MRT）延长。结论 延胡索与白芷配伍具有协同作用，能促进延胡索甲素、延胡索乙素、原阿片碱、欧前胡素及异欧前胡素在大鼠脑组织中的分布，以上化合物可作为元胡止痛方的Q-marker。

Objective To investigate the effect of compatibility on brain tissue distribution in rat of corydaline, tetrahydropalmatine, protopine, imperatorin and isoimperatorin in Corydalis Rhizoma and Angelicae Dahuricae Radix, and to provide further experimental evidence for confirming the Q-marker of Yuanhu Zhitong Prescription. Methods After oral administration of Corydalis Rhizoma, Angelicae Dahuricae Radix, and Yuanhu Zhitong Prescription extracts respectively, the concentration of five compounds in brain tissue samples at different time points was determined by UPLC-MS/MS, and the effect of compatibility on brain tissue distribution was further evaluated by kinetic parameters. Results Compared with single-herb group, AUC and C_max of corydaline, tetrahydropalmatine and protopine in Yuanhu Zhitong Prescription group were increased significantly, and MRT of imperatorin and isoimperatorin were prolonged at the same time. Conclusion Corydalis Rhizoma and Angelicae Dahuricae Radix exist synergistic effect, the compatibility of these two herbs promote brain tissue distribution of corydaline, tetrahydropalmatine, protopine, imperatorin and isoimperatorin, which can be used as Q-marker of Yuanhu Zhitong Prescription.

国家自然科学基金资助项目（81430096）；天津市自然科学基金项目（16JCYBJC28300）