【作者】 石迎迎；

【导师】 李晓天；

【作者基本信息】 郑州大学 ， 药理学， 2012， 硕士

【摘要】 背景：冬凌草乙素作为冬凌草的抗肿瘤有效成分,已有研究表明其具有显著的抗血管原活性,能显著抑制人骨髓瘤细胞、肝癌细胞的增殖并诱导凋亡,更有效地抑制乳腺癌细胞的生成和增殖。这些研究表明,冬凌草乙素有望成为一种天然的抗肿瘤新药。但到目前为止,尚未见有关用高效液相法测定Beagle犬血浆中冬凌草乙素的浓度,以及报道其在Beagle犬体内的药动学特征。目的：本文旨在建立一种专属性强、操作简便的高效液相色谱检测方法,用来测定Beagle犬血浆中冬凌草乙素的浓度,阐明冬凌草乙素静脉注射后在Beagle犬体内的药代动力学特性,为冬凌草乙素进一步的开发利用提供依据。方法：500μL含冬凌草乙素的Beagle犬血浆样品中加入20μL内标非那西丁,经乙酸乙酯萃取处理后,以甲醇-0.5%三乙胺(34：66,v/v)为流动相,流速为1mL/min,进样量：20μL。采用C18柱分离,紫外检测器检测,最大吸收波长为232nm。结果：冬凌草乙素在50.0～4000ng/mL的范围内呈良好的线性关系(r2=0.9995),最低定量限达50.0ng/mL。样品在血浆中的提取回收率大于80%,日内和日间的RSD均小于10%,符合生物样品分析要求。血浆样品预处理操作简便,且内源性物质不干扰测定。将所得冬凌草乙素在犬体内的血药浓度-时间数据,用3P97软件拟合,以AIC值为拟合度指标确定所采用的房室模型,并求算冬凌草乙素在犬体内的各项药代动力学参数。结论：本文首次建立了Beagle犬血浆中冬凌草乙素的高效液相色谱分析方法。本文所建立的定量分析方法快速、灵敏、易操作,成功的用于冬凌草乙素在Beagle犬体内的药物动力学研究。更多还原

【Abstract】 Background:Ponicidin is one of the major anti-tumor constituents of Rabdosia rubescens. Studies have shown that it has significant anti-angiogenic activity of the original. Laboratory data have also shown that ponicidin can significantly inhibit the human myeloma cell, liver cell proliferation and induce apoptosis, more effectively inhibit thegeneration and proliferation of breast cancer cells. These studies indicate that ponicidin is expected to become a natural anti-tumor drugs. But so far, the concentration of ponicidin has not been measured in the Beagle dog plasma with HPLC, and no information about the pharmacokinetic characteristics of it in Beagle dog was reported.Objective:This article aims to establish a specific, simple high-performance liquid chromatography method used to determine the concentration of ponicidin in the Beagle dog plasma, and to clarify the pharmacokinetic characteristics of ponicidin in Beagle dog after the intravenous injection. These studies provide a basis for further development and utilization on ponicidin.Method:500μL Beagle dog plasma samples containing ponicidin, added20μL phenacetin solution as the internal, was extracted by ethyl acetate. An C18column was used to separate ponicidin in plasma with methanol-0.5%triethylamine (34:66,v/v) as mobile phase, at a flow rate of1mL/min,injection volume:20μL. Uvdetector was used and the maximun absorption wavelength was set at232nm.Results:Ponicidin in the range50.0～4000ng/mL showed a good linear relationship (r2=0.9995), and the lowest limit of quantification (LLOQ) achieved was50.0ng/mL. The extraction recoveries of sample in the plasma were greater than80%, and the intra-and inter-day precision were less than10.0%, in line with biological sample analysis requirements. Plasma sample preparation was simple and did not interfere with the determination of the endogenous substances. The plasma concentration-time data obtained in dogs, fitted with3P97software to AIC as a goodness of fit index was used to determine the compartment model and calculate the pharmacokinetic parameters.Conclusion:The HPLC method was established for the first time to analyze ponicidin in Beagle dog plasma. This quantitative analysis method established was rapid, sensitive, easy to operate. The method was successfully used to study the pharmacokinectic of ponicidin in Beagle dog plasma.更多还原