中国中药杂志

2014, v.39(10) 1928-1932

[打印本页] [关闭]
本期目录(Current Issue) | 过刊浏览(Past Issue) | 高级检索(Advanced Search)

脉络宁注射液中5种酚酸类成分血药浓度的LC-MS/MS测定及大鼠体内药代动力学研究
Determination of plasma concentration of five phenolic acid by LC-MS /MS and study of pharmacokinetics in rats after Mailuoning injection

吴婷;张军;李长印;谈恒山;居文政;徐向阳;
WU Ting;ZHANG Jun;LI Chang-yin;TAN Heng-shan;JU Wen-zheng;XU Xiang-yang;Affiliated Hospital of Nanjing University of Traditional Chinese Medicine;General Hospital of Nanjing Military Area Command;Technology Center of Jinling Pharmaceutical Company;

摘要(Abstract):

通过建立准确灵敏的LC-MS/MS法,测定8只SD大鼠,单剂量尾静脉注射(4 mL·kg-1)脉络宁注射液后,血浆中绿原酸、咖啡酸、3,4-二咖啡酰基奎宁酸(3,4-DCQA)、阿魏酸、肉桂酸的浓度,所测数据使用DASver 1.0软件进行处理,计算主要药动学参数。结果显示,绿原酸、咖啡酸、3,4-DCQA、阿魏酸、肉桂酸的线性范围分别为2.0061 027μg·L-1(r=0.999 6),1.9531 027μg·L-1(r=0.999 6),1.9531 000μg·L-1(r=0.999 7),28.511 000μg·L-1(r=0.999 7),28.511.459×104μg·L-1(r=0.998 9),1.8361.459×104μg·L-1(r=0.998 9),1.836940.0μg·L-1(r=0.997 7),4.780940.0μg·L-1(r=0.997 7),4.7802 447μg·L-1(r=0.998 6)。方法学考察5种酚酸类成分血浆样品反复冻融3次、-75℃放置20 d、室温放置4 h以及血浆样品处理后的分析物放置24 h的稳定性均良好,日内、日间变异系数(RSD)小于5.0%,精密度和准确度等均符合生物样品分析的要求。大鼠体中绿原酸药代参数:t1/2为(49.78±12.81)min,AUC0-t为(123.55±14.82)mg·min·L-1,CL为(0.004 3±0.000 5)L·min-1;咖啡酸药代参数t1/2为(36.65±10.59)min,AUC0-t为(91.67±11.77)mg·min·L-1,CL为(0.005 7±0.000 7)L·min-1;3,4-DCQA药代参数:t1/2为(50.08±13.78)min,AUC0-t为(278.34±31.82)mg·min·L-1,CL为(0.001 6±0.000 2)L·min-1;阿魏酸药代参数t1/2为(51.39±15.52)min,AUC0-t为(34.72±4.67)mg·min·L-1,CL为(0.000 4±0.000 1)L·min-1;肉桂酸药代参数t1/2为(74.42±18.32)min,AUC0-t为(34.63±4.82)mg·min·L-1,CL为(0.007 7±0.001 1)L·min-1。该文所建立的LC-MS/MS适用于绿原酸等5种酚酸类成分的药代动力学研究。
To establish a LC-MS/MS method for quantification of chlorogenic acid,caffeic acid,3,4-DCQA,ferulic acid and cinnamic acid in rats plasma and study its pharmacokinetics after administration of Mailuoning injection at a single dose to rats.Plasma samples were acidified with hydrochloric acid and extracted with ethyl acetate.The analytes were determined by LC-MS-MS using a ZOBAX SB C18column with a mobile phase of methanol-water(containing 2 mmol ·L- 1ammonium acetic)(60∶ 40) at a flow rate of0.5 mL·min- 1and detected using ESI with negative ionization mode.Ions monitored in the multiple reaction monitoring(MRM)mode were m /z 353.1 /191.0 [M- H]-for chlorogenic acid,m /z 178.9 /134.9 [M- H]-for caffeic acid,m /z 515.2 /353.0 [M- H]-for 3,4-DCQA,m /z 193.0 /133.9 [M- H]-for ferulic acid,m /z 146.9 /102.9 [M- H]-for cinnamic acid and m /z 246.0 /125.8[M-H]-for tinidazole(IS).After administration of Mailuoning injection at a single dose to eight Sprague-Dawley rats,the concentrations of chlorogenic acid,caffeic acid,3,4-DCQA,ferulic acid and cinnamic acid in plasma were determined by LC-MS /MS method.The main pharmacokinetics parameters of measured data were caluculated by using DASver 1.0 software.The linear concentration ranges of the calibration curves for chlorogenic acid,caffeic acid,3,4-DCQA and cinnamic acid were 2.006-1 027 μg·L- 1(r =0.999 6),1.953-1 000 μg·L- 1(r =0.999 7),28.51-1.459 ×104μg·L- 1(r =0.998 9),1.836-940.0 μg·L- 1(r =0.997 7)and 4.780-2 447 μg·L- 1(r =0.998 6)respectively.The inner and inter-days relative standard deviations were both less than 5.0%,indicating legitimate precise and accuracy to the requirement of biological sample analysis.For chlorogenic acid,the pharmacokinetic parameter t1 /2,AUC0-tand CL were(49.78 ± 12.81) min,(123.55 ± 14.82) mg·min·L- 1and(0.004 3 ± 0.000 5) L·min- 1,respectively.For caffeic acid,the pharmacokinetic parameter t1 /2,AUC0-tand CL were(36.65 ± 10.59) min,(91.67 ± 11.77)mg·min·L- 1and(0.005 7 ± 0.000 7) L·min- 1,respectively.For 3,4-DCQA,the pharmacokinetic parameter t1 /2,AUC0-tand CL were(50.08 ± 13.78) min,(278.34 ± 31.82) mg·min·L- 1and(0.001 6 ± 0.000 2) L·min- 1,respectively.For ferulic acid,the pharmacokinetic parameter t1 /2,AUC0-tand CL were(51.39 ± 15.52) min,(34.72 ± 4.67) mg · min · L- 1and(0.000 4 ±0.000 1) L·min- 1,respectively.For cinnamic acid,the pharmacokinetic parameter t1 /2,AUC0-tand CL were(74.42 ± 18.32)min,(34.63 ± 4.82) mg·min·L- 1and(0.007 7 ± 0.001 1) L·min- 1,respectively.The assay method is proved to be sensitive,accurate and convenient.It can be applied to the pharmacokinetic study of chlorogenic acid,caffeic acid,3,4-DCQA,ferulic acid and cinnamic acid.

关键词(KeyWords): 脉络宁注射液;绿原酸;咖啡酸;3,4-DCQA;阿魏酸;肉桂酸;药代动力学;高效液相色谱-质谱联用
Mailuoning injection;chlorogenic acid;caffeic acid;3,4-DCQA;ferulic acid;cinnamic acid;pharmacokinet-ics;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): 吴婷;张军;李长印;谈恒山;居文政;徐向阳;
WU Ting;ZHANG Jun;LI Chang-yin;TAN Heng-shan;JU Wen-zheng;XU Xiang-yang;Affiliated Hospital of Nanjing University of Traditional Chinese Medicine;General Hospital of Nanjing Military Area Command;Technology Center of Jinling Pharmaceutical Company;

扩展功能
本文信息
服务与反馈
本文关键词相关文章
本文作者相关文章
中国知网
分享