医药导报Issue(9)：1146-1149,4.DOI:10.3870/j.issn.1004-0781.2015.09.006
大鼠血浆 PA-824的 HPLC-MS/MS 测定及药动学研究∗
Determination of PA-824 in Rat Plasma by HPLC-MS/MS and Application in Pharmaco-kinetic Study
摘要
Abstract
Objective To develop an HPLC-MS/ MS method for quantitative determination of PA-824 in rat plasma and to study the pharmacokinetics of PA-824 in rat after oral administration. Methods An HPLC-MS/ MS method was developed and validated for determination of PA-824 in rat plasma using metronidazole as internal standard.The proteins in plasma samples were precipitated with methanol,and PA-824 was enriched for analysis by HPLC-MS/ MS.An Inertsil® ODS3 C18 column (150 mm×4.6 mm,5 μm) was applied with mobile phase composed of methanol- 0.03% triethylamine (TEA) in water (90:10) ,at a flow rate of 0. 5 mL • min-1 and column temperature of 30 ℃ . Quantitation was performed on a triple quadrupole mass spectrometer applying electrospray ionization technique and operating in multiple reaction monitoring (MRM) and positive ion mode with transitions at 360.1/ 175.0 for PA-824 and 172.0/ 128.0 for metronidazole.The concentration of PA-824 in plasma was tested after oral administration at various time points and the data were processed with software DAS.2.0. Results The standard calibration curve for spiked rat plasma containing PA-824 was linear over the range of 0. 1 - 10. 0 μg•mL-1 . The recoveries obtained for PA-824 were greater than 92.13%.Intra-day and inter-day coefficient of variation were less than 6.6%.After oral administration,the main pharmacokinetic parameters were AUC(0-t) : ( 3 297. 503 ± 320. 958) mg • L-1 • min-1 , AUC(0-∞ ) :(3 558.315±338.860)mg•L-1•min-1 ,tmax:(360.000±64.143)min,Cmax:(3.5±0.3)μg•mL-1 . Conclusion The method is rapid,accurate,simple,and successfully applied in a pharmacokinetic study of fixed dose oral administration of PA-824 in rats.关键词
PA-824/液相色谱-质谱联用/药动学/大鼠Key words
PA-824/High performance liquid chromatograph-tandem mass spectrometer/Pharmacokinetics/Rats分类
医药卫生引用本文复制引用
刁春妍,马江微,弥乐,赵乃千,王力彬,刘雪英..大鼠血浆 PA-824的 HPLC-MS/MS 测定及药动学研究∗[J].医药导报,2015,(9):1146-1149,4.基金项目
陕西省协同创新项目(2014XT-26) （2014XT-26）
