栀子-闹羊花配伍对大鼠血浆中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的药动学影响  

Effect of Compatibility of Gardeniae Fructus and Rhododendri Mollis Flos on Pharmacokinetics of Rhodojaponin Ⅱ and Rhodojaponin Ⅲ in Rat Plasma

作　　者：张小琼[1] 李婷 王惠玉 刘楠 郭小红[1] ZHANG Xiaoqiong;LI Ting;WANG Huiyu;LIU Nan;GUO Xiaohong(Department of Pharmacy,Chongqing Hospital of Traditional Chinese Medicine,Chongqing 400021,China;School of Pharmacy,Chongqing University of Medical Sciences,Chongqing 400016,China;Shimadzu Enterprise Management(China)Co.,Ltd.,Beijing Branch,Beijing 100020,China;Department of Technology Research and Development,Zhejiang CONBA Pharmaceutical Co.,Ltd.,Lanxi 321100,China)

机构地区：[1]重庆市中医院药剂科,重庆400021 [2]重庆医科大学药学院,重庆400016 [3]岛津企业管理(中国)有限公司北京分公司,北京100020 [4]浙江康恩贝集团医疗保健品有限公司技术研发部,浙江兰溪321100

出　　处：《中国现代应用药学》2023年第24期3352-3359,共8页Chinese Journal of Modern Applied Pharmacy

基　　金：国家自然科学基金项目(82104398);重庆市自然科学基金面上项目(cstc2020jcyj-msxmX0568,cstc2021jcyj-msxmX0409);重庆英才·创新创业示范团队(CQYC201903172)。

摘　　要：目的考察栀子与闹羊花配伍对闹羊花中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ药动学的影响。方法建立LC-MS/MS测定大鼠血浆中闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的分析方法,并用此方法测定大鼠口服给予闹羊花与栀子配伍液及闹羊花单煎液后大鼠体内的闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的血药浓度,计算其药动学参数并统计分析。结果闹羊花毒素Ⅱ在1~200 ng·mL^(–1)、闹羊花毒素Ⅲ在1~100 ng·mL^(–1)内线性关系良好(r>0.999),质控样本精密度均<12%,准确度RSD<20%。栀子配伍闹羊花给药和单独给药后体内闹羊花毒素Ⅱ的AUC_(0–t)分别为(260.44±51.67)和(213.39±59.03) h·ng·mL^(–1),闹羊花毒素Ⅲ的AUC_(0–t)分别为(60.97±22.78)和(22.38±5.55)h·ng·mL^(–1)。与闹羊花单煎给药相比,栀子与闹羊花配伍给药后闹羊花毒素Ⅱ的T_(1/2)和MRT_((0–t))显著升高,闹羊花毒素Ⅲ的AUC_(0–t)、T_(1/2)、T_(max)和CL显著升高。结论栀子与闹羊花配伍给药后使闹羊花毒素Ⅲ在大鼠体内的吸收速度和分布体积增加、消除速率降低,闹羊花毒素Ⅱ和闹羊花毒素Ⅲ的半衰期延长,但不影响闹羊花毒素Ⅱ在大鼠体内的吸收速率。OBJECTIVE To investigate the effects of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos on the pharmacokinetic behavior of rhodojaponin Ⅱ and rhodojaponin Ⅲ of Rhododendri Mollis Flos.METHODS LC-MS/MS of rhodojaponin Ⅱ and rhodojaponin Ⅲ in plasma of rats was developed.The method was then applied to study the blood concentrations of rhodojaponin Ⅱ and rhodojaponin Ⅲ in rats after oral compatibility administration of Gardeniae Fructus and Rhododendri Mollis Flos and single decoction administration of Rhododendri Mollis Flos,respectively,then their pharmacokinetic parameters were calculated and statistical analysed.RESULTS The calibration curve was good linearity(r>0.999) in the range of1–200 ng·mL^(–1) for rhodojaponin Ⅱ and 1–100 ng·mL^(–1) for rhodojaponin Ⅲ,the precision of quality control samples was less than12%and the accuracy was less than 20%.After administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos and Rhododendri Mollis Flos alone,the AUC_(0–t) of rhodojaponin Ⅱ in vivo was(260.44±51.67) and (213.39±59.03)h·ng·mL^(–1),respectively,and the AUC_(0–t) of rhodojaponin Ⅲ was (60.97±22.78) and (22.38±5.55)h·ng·mL^(–1),respectively.Compared with single decoction of Rhododendri Mollis Flos administration group,the T_(1/2) and MRT_((0–t) )of the rhodojaponin Ⅱ were significantly increased,the AUC_(0–t),T_(1/2),T_(max) and CL of the rhodojaponin Ⅲ were also significantly rised after administration of compatibility of Gardeniae Fructus and Rhododendri Mollis Flos.CONCLUSION After the compatibility of Gardeniae Fructus and Rhododendri Mollis Flos,the rate of absorption and the distribution volume are increased of rhodojaponin Ⅲ in rats,while the elimination rate has decreased,the T_(1/2) of rhodojaponin Ⅱ and rhodojaponin Ⅲ are extended,but don’t affect the absorption rate of rhodojaponin Ⅱ in rats.

关 键 词：闹羊花 栀子 配伍给药 药动学 闹羊花毒素Ⅲ 闹羊花毒素Ⅱ 

分 类 号：R969.1[医药卫生—药理学]