三叶青藤叶配方颗粒大鼠体内药代动力学生物等效性评价  

Pharmacokinetic and bioequivalency of dispensing granules of Tetrastigma Hemsleyanum aerial parts in rats

作　　者：谢平[1] 余文静 陈丹[1] 刘秀棉 洪丽婷 熊朝栋 XIE Ping;YU Wen-jing;CHEN Dan;LIU Xiu-mian;HONG Li-ting;XIONG Chao-dong(Department of Pharmacy,Fujian University of Traditional Chinese Medicine,Fuzhou 350122,China)

机构地区：[1]福建中医药大学药学院,福州350122

出　　处：《药物分析杂志》2020年第11期2017-2032,共16页Chinese Journal of Pharmaceutical Analysis

基　　金：福建省科技引导性项目(2019Y0037);福建省中医药科技项目(2017FJZYZY202);福建省科技计划项目(2010Y2004)。

摘　　要：目的:研究建立同时测定大鼠血浆中三叶青藤叶配方颗粒5个效应组分的UPLC-MS定量分析方法,比较配方颗粒与汤剂在大鼠体内的药动学特性及生物等效性。方法:运用超高效液相色谱-质谱联用分析(UPLC-MS/MS)法,建立同时测定三叶青藤叶配方颗粒5个主要效应组分新绿原酸、绿原酸、荭草苷、异荭草苷、异荭草苷-2′-O-鼠李糖苷大鼠血浆血药浓度的定量分析方法,比较大鼠分别口服给药三叶青藤叶配方颗粒与汤剂后的血药浓度、口服生物利用度和主要药动学参数,及其药动学特性,评价其生物等效性。结果:5个主要效应组分的药动学参数分别为Cmax新绿原酸:配方颗粒(39.08±0.85)ng·m L^-1、汤剂(37.68±0.46)ng·m L^-1,绿原酸:配方颗粒(67.13±0.59)ng·m L^-1、汤剂(65.65±1.02)ng·m L^-1,荭草苷:配方颗粒(51.92±0.27)ng·m L^-1、汤剂(51.90±0.26)ng·m L^-1,异荭草苷:配方颗粒(12.89±0.05)ng·m L^-1、汤剂(12.67±0.12)ng·m L^-1,异荭草苷-2′-O-鼠李糖苷:配方颗粒(119.45±0.81)ng·m L^-1、汤剂(117.70±0.53)ng·m L^-1;AUC(0-∞)新绿原酸:配方颗粒(523.95±5.47)ng·h·L^-1、汤剂(492.82±89.41)ng·h·L^-1,绿原酸:配方颗粒(400.19±57.48)ng·h·L^-1、汤剂(390.83±6.56)ng·h·L^-1,荭草苷:配方颗粒(553.67±9.175)ng·h·L^-1、汤剂(591.72±482)ng·h·L^-1,异荭草苷:配方颗粒(564.50±23.24)ng·h·L^-1、汤剂(493.08±33.67)ng·h·L^-1,异荭草苷-2′-O-鼠李糖苷:配方颗粒(665.78±10.41)ng·h·L^-1、汤剂(651.06±2.14)ng·h·L^-1。方差分析结果表明,配方颗粒与汤剂比较,5个效应组分的药动学参数Cmax及AUC(0-∞)均无显著性差异,双单侧检验法在90%的置信度下检验,配方颗粒与汤剂具有生物等效性。结论:三叶青藤叶配方颗粒与饮片汤剂的药代动力学特性表征无显著性差异,两剂型具有生物等效性,为三叶青藤叶配方颗粒替代饮片汤剂提供了临床应用实验基础。Objective:To establish an UPLC-MS quantitative analysis method to simultaneously determine the five active ingredients of the dispensing granules of the aerial parts of Tetrastigma Hemsleyanum in rat blood plasma,so as to evaluate the pharmacokinetics and bioequivalence of dispensing granules and decoction of the aerial parts of Tetrastigma Hemsleyanum.Methods:Using ultra high performance liquid chromatography-mass spectrometry(UPLC-MS),a quantitative analysis method to simultaneously determine the five active ingredients of the dispensing granules of the aerial parts of Tetrastigma Hemsleyanum,i.e.neochlorogenic acid,chlorogenic acid,orientin,isoorientin,and isoorientin-2’-O-rhamnoside,in rat blood plasma was established.The drug concentration in blood plasma,oral bioavailability,the main pharmacokinetic parameters,and the pharmacokinetic characteristics of the orally administered granules and decoction in rats were compared to evaluate their bioequivalence.Results:The Cmax values of the five active ingredients were neogengenic acids:dispensing granules(39.08±0.85)and decoction(37.68±0.46)ng·mL^-1,chlorogenic acid(67.13±0.59)and(65.65±1.02)ng·mL^-1,orientin(51.92±0.27)and(51.90±0.26)ng·mL^-1,isoorientin(12.89±0.05)and(12.67±0.12)ng·mL^-1,and isoorientin-2’-O-rhamnoside(119.45±0.81)and(117.70±0.53)ng·mL^-1.The AUC(0-∞)values were neogengenic acids:dispensing granules(523.95±5.47)and decoction(492.82±89.41)ng·h·L^-1,chlorogenic acid(400.19±57.48)and(390.83±6.56)ng·h·L^-1,orientin(553.67±9.175)and(591.72±482)ng·h·L^-1,isoorientin(564.50±23.24)and(493.08±33.67)ng·h·L^-1,and isoorientin-2′-O-rhamnoside(665.78±10.41)and(651.06±2.14)ng·h·L^-1.The variance analysis showed that there was no significant difference in the Cmax and AUC(0-∞)values between dispensing granules and decoction.The results of two onesided t tests at 90%confidence level indicated that the dispensing granules were bioequivalent to the decoction.Conclusion:There is no significant difference in pharmacokine

关 键 词：三叶青藤叶配方颗粒 汤剂 药动学 等效性试验 新绿原酸 绿原酸 荭草苷 异荭草苷 异荭草苷-2′-O-鼠李糖苷 

分 类 号：R917[医药卫生—药物分析学]