中国临床药理学与治疗学2007，Vol.12Issue(6)：676-681,6.
完整大鼠连续间断取血法研究黄芪甲苷的药动学
Pharmacokinetics study of astragaloside Ⅳ by intravenous administration with intermittent blood sampling in intact rats
余俊先 1张淳文 2张银娣 1孙视 3赵人争 2韩嘉媛 2沈建平1
作者信息
- 1. 南京医科大学基础医学院药理系,南京,210029,江苏
- 2. 南京医科大学公共卫生学院卫生检验系,南京,210029
- 3. 江苏省中国科学院植物研究所,南京,210029,江苏
- 折叠
摘要
Abstract
AIM: To establish a sensitive method for quantitative determination of astragaloside Ⅳ (AGS-Ⅳ) in plasma and a preliminary evaluation of its pharmacokinetics parameters in intact rats. METHODS: A liquid chromatography-electrospray ionization-mass spectrometry (LC-ESI-MS) was applied for determining AGS-Ⅳ in plasma by using digoxin as the internal standard (I.S.). Six rats were given AGS-Ⅳ 2.0 mg/kg by intravenous infusion for 5 min. Blood samples were drawn intermittently with each intact rat from left femoral artery at 0.025, 0.05, 0.1, 0.25, 0.5, 1, 2, 4, 6, 10, 14 and 24 h after medication. The samples were prepared by solid phase extraction and analyzed through a triple quadrupole mass spectrometer equipped with an electrospary probe. The samples were monitored in selected ion recording (SIR) mode of positive ions by using target ions at m/z 807.5 for AS- Ⅳand at m/z 803.5 for I.S. RESULTS: Calibration curves were linear over the ranges 1-1 000 ng/mL for AGS-Ⅳ (r=0.9992). The intra-and inter-day assay variability values were less than 6% and 8%, respectively. Extraction recoveries from plasma were 92.8%-98.4% for AGS-Ⅳ and 80.0%-90.9% for digoxin, respectively. The lower limit of quantitation (LLOQ) for AGS-Ⅳ was 0.5 ng/mL. The concentration-time curves of AGS-Ⅳ for each rat were fitted to an open two-compartment model by CAPP program. The pharmacokinetics parameters of AGS-Ⅳ were as following: the elimination half-life (t1/2β), clearance rate (CL), distribution volume at steady state (Vss), and AUC0-∞ were (3.46±0.52) h, (0.47±0.02) L/h, (0.76±0.16) L/kg and (4.27±0.19) μg·mL-1·h, respectively. CONCLUSION: These results show that this method is satisfied for the measurements of pharmacokinetics study for AGS-Ⅳ.关键词
黄芪甲苷/药动学/HPLC-MS/完整大鼠Key words
astragaloside Ⅳ/pharmacokinetics/LC-ESI-MS/intact rats分类
医药卫生引用本文复制引用
余俊先,张淳文,张银娣,孙视,赵人争,韩嘉媛,沈建平..完整大鼠连续间断取血法研究黄芪甲苷的药动学[J].中国临床药理学与治疗学,2007,12(6):676-681,6.
