吴茱萸新碱和二氢吴茱萸新碱是吴茱萸中的固有成分,又是其致肝毒性的潜在物质基础之一。为了深入分析毒性剂量下两种毒性成分的体内作用过程,采用超高效液相色谱-三重四极杆质谱(UPLC-TQD-MS/MS)联用技术,首次建立和验证了同时测定大鼠灌胃吴茱萸提取物后血浆中吴茱萸新碱和二氢吴茱萸新碱的含量测定方法,并进行药代动力学研究。采用乙酸乙酯萃取法处理血浆样品,在优化后的色谱和质谱条件下,进行等度洗脱、多反应监测模式扫描,测定不同采血时间两种成分的血药浓度。通过PK Solver 2.0软件的非房室模型法对数据进行处理,推算两种成分的药动学参数。实验结果表明,吴茱萸新碱和二氢吴茱萸新碱在体内被迅速吸收,血浆中的平均达峰时间分别为0.54±0.10、0.58±0.13 h,平均峰浓度分别为36.38±9.89、22.07±8.34 ng/mL,药时曲线下面积分别为119.8±29.8、67.25±21.12 ng/mL*h。二者的半衰期分别为2.80±0.61 h和3.49±0.74 h,经过约4个半衰期,血中残留量大幅降低。本文为指导吴茱萸的临床合理、安全使用提供了科学依据。
Evocarpine and dihydroevocarpine are the intrinsic components of Euodia rutaecarpa and one of the potential material basis for hepatotoxicity. In order to further analyze the in vivo process of two toxic components at toxic doses, the method for simultaneous determining the content of evocarpine and dihydroevocarpine in plasma after administration of Euodia rutaecarpa extract was established and verified by ultra performance liquid chromatography-triple quadrupole mass spectrometry (UPLC-TQD-MS/MS), and the pharmacokinetic was also studied. The ethyl acetate extraction was used to pretreat plasma samples. Under the optimized conditions of chromatography and mass spectrometry, isometric elution and multi-reaction monitoring mode scanning were carried out to determine the plasma concentration of two components at different blood collection time. The non-atrioventricular model method of PK Solver 2.0 software was used to process the data and calculate the pharmacokinetic parameters of the two components. Experiment results indicated that the evocarpine and dihydroevocarpine were rapidly absorbed in vivo. The average peak time in plasma was 0.54±0.10 and 0.58±0.13, the average peak concentrations were 36.38±9.89 and 22.07±8.34 ng/mL, and the AUC was 119.8±29.8 and 67.25±21.12 ng/mL*h. The blood drug concentration of both decreased fast, and the half-lives were 2.80±0.61 h and3.49±0.74 h. After about 4 half-lives, the amount of residual in blood was very small. This work provides a scientific basis for guiding clinical rational and safe use of Euodia rutaecarpa.