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;

• 1:南京中医药大学药学院
• 2:南京中医药大学附属医院临床药理科
• 3:南京军区总医院临床药理科

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2¹28μg·L-1(r=0.998 1),3128μg·L-1(r=0.998 1),3³84μg·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(Authors): 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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