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目的:建立灵敏、快捷测定大鼠血浆中雪胆甲素浓度的高效液相色谱法(HPLC),并应用于体内药动学特征研究。方法:色谱条件:色谱柱:Dikma Diamonsil C18(250 mm×4.6 mm,5μm),流动相:乙腈∶水(45∶55,v/v),检测波长:212 nm,柱温:35℃,流速:1.0 ml·min-1。采取大鼠静脉注射给药途径,于不同时间点采血测定血浆药物浓度,并用DAS 2.0计算药动学参数。结果:雪胆甲素血药浓度在0.146~14.060μg·ml-1范围内线性关系良好(r=0.999 3);方法回收率为99.02%~104.22%;提取回收率为84.74%~86.80%;日内、日间精密度RSD均<5%,稳定性考察符合要求。应用此法测定大鼠尾静脉注射给药后的血药浓度并计算主要药动学参数,1.0,2.0,4.0 mg·kg-1三个剂量组静脉给药后在大鼠体内均符合三室模型,主要药动学参数分别为t1/2β(h):0.732±0.151,0.681±0.055,0.667±0.064;Vd(L·kg-1):0.147±0.089,0.131±0.095,0.153±0.047;CL(L·h-1·kg-1):0.287±0.031,0.304±0.063,0.318±0.029和AUC0→∞(mg·h·L-1):3.646±1.124,4.916±1.227,9.385±1.419。结论:该法快速、简便、准确,符合生物样品测定需求,可用于药动学研究。雪胆甲素静脉注射给药后在体内呈三室模型,代谢较快,具有线性动力学特征。
OBJECTIVE: To establish a sensitive and rapid HPLC method for the determination of chlorococlac in plasma of rats and to study its pharmacokinetics in vivo. Methods: The chromatographic conditions were as follows: column: Dikma Diamonsil C18 (250 mm × 4.6 mm, 5 μm), mobile phase: acetonitrile: water : 1.0 ml · min-1. The route of intravenous injection in rats was taken, blood samples were collected at different time points to determine plasma drug concentration, and pharmacokinetic parameters were calculated using DAS 2.0. Results: The linear range of the drug concentration was 0.146 ~ 14.060μg · ml-1 (r = 0.999 3). The recoveries were in the range of 99.02% -104.22%. The recovery rates were 84.74% -86.80%. Days, day precision RSD <5%, the stability of the inspection to meet the requirements. This method was used to determine the plasma concentration of rat tail vein after injection and calculate the main pharmacokinetic parameters, 1.0,2.0,4.0 mg · kg-1 three dose groups in rats after intravenous administration are in line with the three-compartment model , The main pharmacokinetic parameters were t1 / 2β (h): 0.732 ± 0.151,0.681 ± 0.055,0.667 ± 0.064; Vd (L · kg -1): 0.147 ± 0.089,0.131 ± 0.095,0.153 ± 0.047; L · h -1 · kg -1): 0.287 ± 0.031,0.304 ± 0.063,0.318 ± 0.029 and AUC0 → ∞ (mg · h · L -1): 3.646 ± 1.124, 4.916 ± 1.227, 9.385 ± 1.419. Conclusion: The method is rapid, simple and accurate, which can meet the needs of biological samples and can be used for pharmacokinetic studies. After intravenous injection of snow gall A in the body showed a three-compartment model, rapid metabolism, with linear kinetic characteristics.