二妙丸与三妙丸中4种生物碱在正常和关节炎模型大鼠体内的药动学与组织分布差异  

Pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats

作　　者：李兵杰 葛文静 单朋涛 王慧森[2] 刘明[2] 李更生[2] 梁瑞峰 LI Bing-jie;GE Wen-jing;SHAN Peng-tao;WANG Hui-sen;LIU Ming;LI Geng-sheng;LIANG Rui-feng(School of Pharmacy,Henan University of Chinese Medicine,Zhengzhou 450046,China;Institute of Chinese Materia Medica,Henan Academy of Chinese Medicine,Zhengzhou 450004,China)

机构地区：[1]河南中医药大学药学院,河南郑州450046 [2]河南省中医药研究院中药研究所,河南郑州450004

出　　处：《中国中药杂志》2023年第7期1943-1950,共8页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金项目(81873022);河南省中医药科研专项(20-21ZY1029);河南省省属科研机构基本科研业务费项目(2004820)。

摘　　要：考察二妙丸与三妙丸中4种生物碱在正常和关节炎模型大鼠体内的药动学与组织分布差异。通过注射弗氏完全佐剂建立模型大鼠,采用超高效液相色谱串联质谱(UPLC-MS/MS),正离子多反应监测模式检测正常大鼠和模型大鼠分别灌胃二妙丸与三妙丸后血浆和组织中4种生物碱成分,比较4种活性成分的药动学和组织分布差异,探讨牛膝对三妙丸主要成分的影响。建立了同时检测4种生物碱的UPLC-MS/MS方法,该方法专属性、线性关系、准确度、精密度、稳定性等均符合要求。药动学研究发现,与正常大鼠比较,模型大鼠灌胃二妙丸后,黄柏碱、木兰花碱、小檗碱和巴马汀的AUC和C_(max)明显降低,清除率显著增加,肝、肾和关节中4种生物碱的分布浓度、组织/血浆浓度比明显减少;牛膝可增加模型大鼠体内黄柏碱、小檗碱、巴马汀的AUC,降低清除率,显著增加4种生物碱在肝、肾和踝关节中的分布,但对正常大鼠体内4种生物碱的药动学及组织分布未有明显影响,提示牛膝可能通过增加关节炎状态下三妙丸有效成分的组织分布,发挥引经作用。This work aimed to investigate the differences of pharmacokinetics and tissue distribution of four alkaloids in Ermiao Pills and Sanmiao Pills in normal and arthritic model rats.The rat model of arthritis was established by injecting complete Freund's adjuvant,and ultra-high performance liquid chromatography-tandem mass spectrometry(UPLC-MS/MS)in the positive ion multiple reaction monitoring(MRM)mode was used for the determination of four alkaloids in plasma and tissues of normal and arthritic rats after administration of Ermiao Pills and Sanmi ao Pills,respectively.The differences in pharmacokinetics and tissue distribution of the four active components were compared,and the effect of Achyranthis Bidentatae Radix on the major components of Sanmiao Pills was explored.This study established an UPLC-MS/MS for simultaneous determination of four alkaloids,and the specificity,linearity,accuracy,precision,and stability of this meth od all met the requirements.Pharmacokinetics study found that as compared with normal rats,the AUC and C_(max) of phellodendrine,magnoflorine,berberine and palmatine in model rats were significantly decreased after administration of Ermiao Pills,the clearance rate CL/F was significantly increased,and the distribution and tissue/plasma concentration ratio of the fou r alkaloids in the liver,kidney,and joint were significantly reduced.Achyranthis Bidentatae Radix increased the AUC of phellodendrine,berberine,and palmatine,reduced the clearance rate,and significantly increased the distribution of the four alkaloi ds in the liver, kidney, and joints in arthritic rats. However, it had no significant effect on the pharmacokinetics and tissue distrib utionof the four alkaloids in normal rats. These results suggest that Achyranthis Bidentatae Radix may play a guiding ro le inmeridian through increasing the tissue distribution of effective components in Sanmiao Pills under arthritis states.

关 键 词：牛膝 二妙丸 三妙丸 药代动力学 组织分布 引经 

分 类 号：R285.5[医药卫生—中药学]