姜丽;高萌;屈飞;李惠兰;余兰彬;饶毅;王跃生;徐国良;
JIANG Li;GAO Meng;QU Fei;LI Hui-lan;YU Lan-bin;RAO Yi;WANG Yue-sheng;XU Guo-liang;Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine,Jiangxi University of Traditional Chinese Medicine;School of Basic Medicine,Jiangxi University of Traditional Chinese Medicine;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine;National Engineering Research Center for Solid Preparations of Chinese Herbal Medicines;Institute of Chinese Materia Medi

• 1:江西中医药大学中医基础理论分化发展研究中心
• 2:江西中医药大学基础医学院
• 3:江西中医药大学药学院
• 4:中药固体制剂制造技术国家工程研究中心

摘要(Abstract)：

建立麻杏石甘汤中甘草苷、甘草素、甘草次酸、苦杏仁苷、野黑樱苷、麻黄碱、伪麻黄碱、甲基麻黄碱等8种有效成分在大鼠血浆中药物浓度的LC-MS/MS测定方法,并应用该法研究麻杏石甘汤在正常及RSV肺炎感染模型大鼠体内8种成分药代动力学过程和差异。正常及模型大鼠灌胃麻杏石甘汤后,于不同时间点从眼底静脉丛取血,其中麻黄中成分以四氢巴马汀为内标,其余成分以氯霉素为内标,血浆样品经前处理后,上清液用N2吹干,残渣用甲醇复溶;以乙腈-0.1%甲酸水为流动相梯度洗脱,采用ESI源,麻黄中的成分以正离子模式扫描,其余成分以负离子模式扫描,多反应监测模式(MRM)检测各有效成分血药浓度;用Win Nonlin 4.1药动学软件和SPSS 17.0软件分别计算各给药组药动学参数并进行统计分析。结果表明,甘草苷、甘草素、甘草次酸、苦杏仁苷、野黑樱苷、麻黄碱、伪麻黄碱、甲基麻黄碱等8个有效成分血浆质量浓度分别在1.04¹ 040,1.041 040,1.04¹ 040,0.891 040,0.89⁴45,1.05445,1.05⁴ 200,1.254 200,1.25² 490,0.32 490,0.3⁴80,0.3480,0.3⁴80,0.3480,0.3⁴80μg·L-1线性良好;上述各成分精密度、回收率、稳定性均符合生物样品定量要求。造模后,除甘草次酸因数据缺失未能得到完整的药动学参数,其余各成分Cmax和AUC0-t均显著高于正常组,CL均显著低于正常组,提示病理状态大鼠可能通过降低清除率进而增加各成分的吸收。该方法可以准确、灵敏检测大鼠血浆中麻杏石甘汤中8个有效成分的血药浓度。大鼠经RSV肺炎感染后,可增加对麻杏石甘汤的吸收。
To establish a LC-MS/MS method to determine the concentrations of liquiritin,glycyrrhizin,glycyrrhetinic acid,amygdalin,amygdalin prunasin,ephedrine,pseudoephedrine and methylephedrine of Maxing Shigan decoction in rat plasma,and study the differences on their pharmacokinetic process in normal rats and RSV pneumonia model rats. After normal rats and RSV pneumonia model rats were orally administered with Maxing Shigan decoction,the blood was collected from retinal vein plexus of different time points. Specifically,tetrahydropalmatine was taken as internal standard for determining ephedrine,while chloramphenicol was taken as internal standard for determining other components. After plasma samples were pre-treated as the above,the supernatant was dried with nitrogen blowing concentrator and then redissolved with methylalcohol. The chromatography was eluted with mobile phase consisted of acetonitrile and 0. 1% formic acid solution in a gradient manner. ESI sources were adopted to scan ingredients in ephedra in a positive ion scanning mode and other ingredientsin a negative ion scanning mode. The multiple-reaction monitoring( MRM) method was developed the plasma concentration of each active component. The pharmacokinetic parameters of each group were calculated by using WinNonlin 4. 1 software and put into the statistical analysis. The result showed the plasma concentration of the eight active ingredients,i. e. liquiritin,glycyrrhizin,glycyrrhetinic acid,amygdalin,amygdalin prunasin,ephedrine,pseudoephedrine and methylephedrine within the ranges of 1. 04-1 040,1. 04-1 040,0. 89-445,1. 05-4 200,1. 25-2490,0. 3-480,0. 3-480,0. 3-480 μg·L- 1,with a good linearity and satisfactory precision,recovery and stability in the above ingredients. After modeling,except for glycyrrhetinic acid whose pharmacokinetic parameters were lacked due to the data missing,all of the rest components showed significant higher Cmax,AUC0-tand lower clearance rate( CL) than that of the normal group,indicating the increase in absorption in rats in the pathological state by reducing the clearance rate. The method is accurate and sensitive and so can be used to determine the plasma concentrations of the eight active ingredients in Maxing Shigan decoction. RSV pneumonia-infected rats absorbed more ingredients in Maxing Shigan decoction.

关键词(KeyWords)： 麻杏石甘汤;药代动力学;RSV肺炎;LC-MS/MS
Maxing Shigan decoction;pharmacokinetics;RSV pneumonia;LC-MS/MS

Abstract:

Keywords:

基金项目(Foundation): 国家重点基础研究发展计划(973)项目(2010CB530603)

作者(Authors): 姜丽;高萌;屈飞;李惠兰;余兰彬;饶毅;王跃生;徐国良;
JIANG Li;GAO Meng;QU Fei;LI Hui-lan;YU Lan-bin;RAO Yi;WANG Yue-sheng;XU Guo-liang;Research Center for Differentiation and Development of Basic Theory of Traditional Chinese Medicine,Jiangxi University of Traditional Chinese Medicine;School of Basic Medicine,Jiangxi University of Traditional Chinese Medicine;School of Pharmacy,Jiangxi University of Traditional Chinese Medicine;National Engineering Research Center for Solid Preparations of Chinese Herbal Medicines;Institute of Chinese Materia Medi

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