UPLC-MS/MS测定复方丹参方中丹参酮ⅡA、丹参酚酸B、人参皂苷Rg1及其在大鼠血浆和脑组织的药代动力学研究  

UPLC-MS/MS determination of tanshinone Ⅱ_A,salvianolic acid B and ginsenoside Rg_1 in Fufang Danshen preparation in rat plasma and brain tissues

作　　者：张杰[1,2] 刘胜兰[1] 王慧[3] 阳国平[1] 李劲平[2] 刘世坤[1] 唐智[1] 裴奇[1] 黄攀豪[1] ZHANG Jie LIU Sheng-lan WANG Hui YANG Guo-ping LI Jin-ping LIU Shi-kunl TANG Zhi PEI Qi HUANG Pan-hao(The Third Xiangya Hospital, Central South University, Changsha 410013, China Taian Central Hospital, Taian 271000, China School of Pharmaceutical Sciences, Central South University, Changsha 410013, China)

机构地区：[1]中南大学湘雅三医院,湖南长沙410013 [2]中南大学药学院,湖南长沙410013 [3]泰安市中心医院,山东泰安271000

出　　处：《中国中药杂志》2017年第3期580-586,共7页China Journal of Chinese Materia Medica

基　　金：湖南省自然科学基金项目(2010JJ4082);国家临床药学重点专科建设项目

摘　　要：建立大鼠血浆和脑组织中丹参酮Ⅱ_A(TSⅡ_A)、丹酚酸B(SAB)、人参皂苷Rg_1(GRg_1)的UPLC-MS/MS分析方法,并开展药物动力学研究。选用SD大鼠,单剂量灌胃(ig)复方丹参方,采集血液与脑组织样品,采用UPLC-MS/MS测定血浆和脑组织中TSⅡ_A、SAB和GRg_1的浓度,以Phoenix Win Nolin 6.1药动学程序软件对数据进行非房室模型拟合,采用统计矩法计算药动学参数。经方法学考证,3种成分的峰面积与其在血样及脑组织中的浓度线性关系良好(r>0.992 2);回收率为58.86%~112.1%,日内、日间RSD≤9.7%,准确度及稳定性均符合体内药物分析的要求。大鼠ig给复方丹参方后的血浆药动参数如下:丹参酮Ⅱ_AT_(max)(1.58±0.081)h,C_(max)(725.4±88.20)μg·L^(-1),AUC_(0-t)(2 101.3±124.85)μg·h·L^(-1),MRT_(0-t)(3.66±0.05)h;丹酚酸B T_(max)(1.29±0.21)h,C_(max)(307.9±46.75)μg·L^(-1),AUC_(0-t)(537.4±88.24)μg·h·L^(-1),MRT_(last)(2.08±0.11)h;人参皂苷Rg_1T_(max)(1.42±0.20)h,C_(max)(460.38±154.60)μg·L^(-1),AUC_(0-t)(383.4±88.16)μg·h·L^(-1),MRT_(last)(1.87±0.046)h。脑组织药动参数如下:丹参酮Ⅱ_AT_(max)(0.75±0.22)h,C_(max)(1.41±0.420)ng·g^(-1),AUC_(0-t)(4.34±2.48)ng·h·g^(-1),MRT_(0-t)(4.00±1.90)h;丹酚酸B T_(max)(1.08±0.20)h,C_(max)(21.09±4.850)ng·g^(-1),AUC_(0-t)(14.83±3.160)ng·h·g^(-1),MRT_(0-t)(0.99±0.08)h;人参皂苷Rg_1T_(max)(0.50±0.16)h,C_(max)(130.96±54.220)ng·g^(-1),AUC_(0-t)(136.24±34.350)ng·h·g^(-1),MRT_(0-t)(2.87±0.33)h。该研究所建立的UPLC-MS/MS方法可用于大鼠血浆及脑组织中丹参酮Ⅱ_A、丹酚酸B、人参皂苷Rg_1中的药动学研究。A sensitive and specific ultra-performance liquid chromatography-mass spectrometry（ UPLC-MS/MS） method was developed for analysis of tanshinone Ⅱ_A（ TSⅡ_A）,salvianolic acid B（ SAB） and ginsenoside Rg_1（ GRg_1） in rat plasma and brain tissues.Male healthy Sprague-Dawley（ SD） rats were orally given single dose of Fufang Danshen preparation（ TS Ⅱ_A60 mg·kg^（-1）,SAB 300mg·kg^（-1）,GRg_1150 mg·kg^（-1）,borneol 300 mg·kg^（-1））,and their blood samples and brain tissues were collected at different time points. The drug plasma and brain tissue concentrations of the three analytes were determined by UPLC-MS/MS method. Subsequently,the main pharmacokinetics parameters of plasma and brain tissues were calculated by using Phoenix Win Nolin 6. 1 software. The methodological test showed that all of analytes in both plasma and brain homogenate exhibited a good linearity within the concentration range（ r 0. 992 2）. Their mean recoveries were between 58. 86% and 112. 1%. Intra-day and inter-day precisions of the investigated components exhibited RSD≤9. 7%,and the accuracy（ RE） ranged from-9. 68% to 8. 20% at all quality control levels. The results of accuracy and stability meet the requirements for biopharmaceutical analysis. For TSⅡ_A,the pharmacokinetics parameters T_（max）,C_（max）,AUC_（0-t）,MRT_（last）in the plasma were（ 1. 58 ± 0. 081） h,（ 725. 4 ± 88. 20） μg·L^（-1）,（ 2 101. 3 ± 124. 85） μg·h·L^（-1）and（ 3. 66 ±0. 05） h,respectively. For SAB,the pharmacokinetics parameters T_（max）,C_（max）,AUC_（0-t）,MRT_（last）in the plasma were（ 1. 29 ± 0. 21） h,（ 307. 9 ± 46. 75） μg·L^（-1）,（ 537. 4 ± 88. 24） μg·h·L^（-1）and（ 2. 08 ± 0. 11） h,respectively. For GRg_1,the pharmacokinetics parameters T_（max）,C_（max）,AUC_（0-t）,MRT_（last）in the plasma were（ 1. 42 ± 0. 20） h,（ 460. 38 ± 154. 60） μg·L^（-1）,（ 383. 4 ± 88. 16） μg·h·L^（-1）and（ 1. 87 ± 0. 04

关 键 词：UPLC-MS/MS 丹参酮ⅡA 丹酚酸B 人参皂苷RG1 药动学 

分 类 号：R285.5[医药卫生—中药学]