新型红景天苷衍生物pOBz在大鼠体内的药代动力学及血脑屏障穿透性  

Pharmacokinetics and blood-brain barrier penetration of a novel salidroside derivative pOBz in rats

作　　者：罗锐 洪桂祝 聂婧雯 黄私迎 余正双 周彬彬 赖文芳[1] 杨泽霖 LUO Rui;HONG Gui-zhu;NIE Jing-wen;HUANG Si-ying;YU Zheng-shuang;ZHOU Bin-bin;LAI Wen-fang;YANG Ze-lin(College 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,福建福州350122

出　　处：《中国药理学通报》2023年第3期543-548,共6页Chinese Pharmacological Bulletin

基　　金：福建省自然科学基金项目(No 2019J01345,2021J02014,2020J01727);国家自然科学基金项目(No 82174001,81973503);福建省卫健委中青年骨干项目(No 2019-ZQN-74)。

摘　　要：目的建立测定大鼠血浆与脑组织中红景天苷衍生物pOBz的UPLC-MS/MS分析方法,研究pOBz单剂量静脉注射后在大鼠体内药代动力学模式及血脑屏障的穿透性。方法SD大鼠以50 mg·kg^(-1)的剂量尾静脉给药pOBz,采集不同时间点的血浆与脑组织样品,采用UPLC-MS/MS方法测定血浆与脑组织中pOBz的浓度,采用DAS 2.1.1版软件对血药浓度-时间曲线进行统计矩拟合,计算pOBz的药动学参数。结果pOBz在血浆中的线性回归方程为:Y=0.0623X+0.0248,r^(2)=0.999,线性范围0.2~200 mg·L^(-1);在脑匀浆中的线性回归方程为:Y=0.0651 X+0.0317,r^(2)=0.997,线性范围0.2~200 mg·L^(-1)。pOBz在血浆中的半衰期T 1/2为1.03 h,药时曲线下面积AUC_(0-t)为198.4 h·mg·L^(-1),平均驻留时间MRT_(0-t)为0.87 h,清除率CL为0.246 L·h^(-1)·kg^(-1)。给药5 min后即可在脑组织检测到pOBz,浓度为1.21 mg·L^(-1);给药后3 h仍未完全消除。结论pOBz在血浆与脑组织的UPLC-MS/MS方法具有良好的专属性与灵敏度。pOBz可穿透血脑屏障,进入中枢神经系统发挥药理作用。Aim To develop a ultra-high performance liquid chromatography electrospray-ionization tandem mass spectrometry(UPLC-MS/MS)method for the simultaneous determination of salidroside derivative pOBz in rat plasma and brain tissue,and to study the pharmacokinetic profile and penetration of the blood-brain barrier in rats after a single dose intravenous administration of pOBz.Methods SD rats were administered pOBz at a dose of 50 mg·kg^(-1)via tail vein,and plasma and brain tissue samples were collected at different time points.UPLC-MS/MS method was used to determine the concentration of pOBz in plasma and brain tissue.The plasma concentration-time curve was fitted by DAS 2.1.1 software to calculate the pharmacokinetic parameters of pOBz.Results The linear regression equation of pOBz in plasma was:^Y=0.0623 X+0.0248,r^(2)=0.999,and the linear range was 0.2~200 mg·L^(-1);the linearity regression equation in brain homogenate was:^Y=0.0651X+0.0317,r^(2)=0.997,and the linear range was 0.2~200 mg·L^(-1).The half-life T 1/2 of pOBz in plasma was 1.03 h,the area under the drug-time curve AUC_(0-t)was 198.4 h·mg·L^(-1),the mean residence time MRT_(0-t)was 0.87 h,and the clearance rate CL was 0.246 L·h^(-1)·kg^(-1).5 min after administration,pOBz could be detected in brain tissue at a concentration of 1.21 mg·L^(-1);it was not completely eliminated 3 h after administration.Conclusions The UPLC-MS/MS method is accurate and applicable for the pharmacokinetic study of pOBz in plasma and brain homogenate.pOBz can penetrate the blood-brain barrier and exert pharmacological effects in central nervous system.

关 键 词：pOBz 红景天苷衍生物 药代动力学 血脑屏障 UPLC-MS/MS 半衰期 

分 类 号：R332[医药卫生—人体生理学] R282.71[医药卫生—基础医学] R322.81R969.1