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完整大鼠连续间断取血法研究黄芪甲苷的药动学(英文)
Pharmacokinetics study of astragaloside Ⅳ by intravenous administration with intermittent blood sampling in intact rats
【摘要】 目的:建立黄芪甲苷(astragaloside ,AGS-IV)在完整大鼠体内血药浓度的测定方法及初步的药动学评价。方法:运用液质联用仪(HPLC-MS)测定大鼠血浆AGS-IV浓度。6只雄性SD大鼠,AGS-IV溶液静脉给药(2 .0 mg/kg) ,单只大鼠连续取血法,取血点分别为0 .025、0 .05、0 .1、0 .25、0 .5、1、2、4、6、10、14和24 h。固相萃取小柱提取血浆样品,地高辛为内标(I .S.) ,LC-ESI-MS测定血药浓度。AGS-IV的m/z为807 .5 ,内标地高辛的m/z为803 .5。结果: AGS-IV的标准曲线线性范围为1 ~1 000 ng/mL(r=0 .9992) ,日内和日间精密度分别小于6 %和8 %,血浆样品AGS-IV的回收率为92 .8 %~98 .4 %,内标的回收率为80 .0 %~90 .9 %,最低检测限为0 .5 ng/mL。CAPP软件拟合,AGS-IV的消除符合二室模型,药动学参数t1/2β(h) ,CL(L.kg-1.h) ,Vc(L/kg) ,AUC0 -∞(μg·mL-1.h)分别为:3 .46±0 .52 ,0 .47±0 .02 ,0 .76±0 .16和4274±186。结论:连续间断取血法结合HPLC-MS技术,适用于测定AGS-IV在小动物的血药浓度和药动学评价。
【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-IV and 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.
【Key words】 astragaloside Ⅳ; pharmacokinetics; LC-ESI-MS; intact rats;
- 【文献出处】 中国临床药理学与治疗学 ,Chinese Journal of Clinical Pharmacology and Therapeutics , 编辑部邮箱 ,2007年06期
- 【分类号】R285
- 【被引频次】1
- 【下载频次】445