中国中药杂志

2013, v.38(21) 3753-3757

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LC-MS/MS测定大鼠血浆中咖啡酸、绿原酸及其药代动力学研究
Study on determination of caffeic acid,chlorogenic acid in rat plasma and their pharmacokinetics with LC-MS /MS

戴国梁;马世堂;刘史佳;程小桂;臧雨馨;居文政;谈恒山;
DAI Guo-liang;MA Shi-tang;LIU Shi-jia;CHENG Xiao-gui;ZANG Yu-xin;JU Wen-zheng;TAN Heng-shan;College of Pharmacy of Nanjing University of Traditional Chinese Medicine;Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine;Department of Clinical Pharmacology,General Hospital of Nanjing Military Area Command;

摘要(Abstract):

该研究建立大鼠血浆中咖啡酸、绿原酸的LC-MS/MS测定方法,并用于大鼠体内的药代动力学研究。6只SD大鼠,单剂量静脉注射(4 mL·kg-1)灯盏细辛注射液,以替硝唑为内标,用LC-MS/MS测定给药后血浆中的药物浓度,并用DAS 1.0软件计算药动学参数。咖啡酸、绿原酸的线性范围分别为2~128μg·L-1(r=0.998 1),3~384μg·L-1(r=0.998 7)。方法学考察均符合要求。日内、日间变异系数(RSD)均小于10%,精密度和准确度等均符合生物样品分析的要求。大鼠体中咖啡酸药代动力学参数:t1/2β为(130.91±38.77)min,AUC0-t为(4.89±0.96)mg·min·L-1,CL为(0.12±0.02)L·min-1·kg-1;绿原酸药代动力学参数:t1/2β为(49.38±8.85)min,AUC0-t为(9.54±0.95)mg·min·L-1,CL为(0.09±0.003)L·min-1·kg-1。该研究建立的LC-MS/MS分析方法准确灵敏,适于咖啡酸、绿原酸的药代动力学研究。
To establish a LC-MS / MS method to determine caffeic acid,chlorogenic acid in rat plasma and study their pharmacokinetics in rats. Six Sprague-Dawley rats were intravenously injected with 4 mL · kg- 1of Dengzhanxixin injection,respectively. Their drug plasma concentration was determined by LC-MS / MS,with tinidazole as an internal standard. The pharmacokinetic parameters were calculated by DAS 1. 0. The linear concentration ranges of caffeic acid,and chlorogenic acid were 2-128 μg · L- 1(r = 0. 998 1)and 3-384 μg·L- 1(r = 0. 998 7),respectively. The methodological test showed conformance to the requirements. The intraday and inter-day variable coefficients were both less than 10. 0%,indicating that both of legitimate precise and accuracy were in conformity with the requirements of biological sample analysis. For caffeic acid,the pharmacokinetic parameter t 1 /2β,AUC 0-t,and CL were(130. 91 ± 38. 77) min,(4. 89 ± 0. 96) mg·min·L- 1and(0. 12 ± 0. 02) L·min- 1·kg- 1,respectively. For chlorogenic acid,the pharmacokinetic parameter t 1 /2β,AUC 0-t and CL were(49. 38 ± 8. 85) min,(9. 54 ± 0. 95) mg·min·L- 1and(0. 09 ± 0. 003) L·min- 1·kg- 1,respectively. The LC-MS/MS analysis method established in this study was proved to be so accurate and sensitive that it can be applied to the pharmacokinetic study of caffeic acid and chlorogenic acid.

关键词(KeyWords): 灯盏细辛注射液;绿原酸;咖啡酸;大鼠;药代动力学;LC-MS/MS
Dengzhanxixin injection;chlorogenic acid;caffeic acid;rat;pharmacokinetics;LC-MS/MS

Abstract:

Keywords:

基金项目(Foundation): 国家“重大新药创制”科技重大专项(2012ZX09303009-002);; 江苏省中医药领军人才项目(LJ200906);; 江苏高校优势学科建设工程项目(2010)

作者(Author): 戴国梁;马世堂;刘史佳;程小桂;臧雨馨;居文政;谈恒山;
DAI Guo-liang;MA Shi-tang;LIU Shi-jia;CHENG Xiao-gui;ZANG Yu-xin;JU Wen-zheng;TAN Heng-shan;College of Pharmacy of Nanjing University of Traditional Chinese Medicine;Department of Clinical Pharmacology,Affiliated Hospital of Nanjing University of Traditional Chinese Medicine;Department of Clinical Pharmacology,General Hospital of Nanjing Military Area Command;

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