中文摘要：

本实验以尼莫地平为模型药物建立了一种改进的提取并纯化血浆中目标物的方法并将方法应用到药代动力学研究中,方法兼顾了HPLC检测中的药物回收率及杂质清除率。首先使用纯甲醇沉淀样品中的血浆蛋白,之后把上清液浓缩挥干。使用10%到100%的甲醇溶液复溶残留物以考察甲醇浓度对药物回收率及杂质清除率的影响。以色谱图中的杂质峰强度及药物回收率作为指标分析,发现30%甲醇作复溶溶剂可以兼顾药物回收率及杂质清除率。标准曲线在血药浓度为2–160 ng/m L范围内线性关系良好（r^2≥0.999）,定量限（LOQ）为2 ng/m L。在三个浓度水平的质控样品验证下,日内及日间精密度均小于15%,准确度处于–1.70%~5.88%。与已有方法相比,使用该方法处理后的样品可在尼莫地平的最大吸收波长238 nm下检测,定量限减小至2 ng/m L。改进后的方法成功应用到尼莫地平在大鼠体内的药代动力学研究及盐酸利多卡因的样品处理中。

英文摘要：

In order to prepare samples for HPLC analysis with maximum drug recovery and impurity elimination, a revised method for the extraction and purification of a target substance from plasma was developed and applied in a pharmacokinetic study with Nimodipine as a model drug. After protein precipitation of a plasma sample using pure methanol and evaporation of the supernatant to dryness, methanol of various concentrations from 10% to 100% were used to dissolve the remaining residues with the goal of maximizing drug recovery and impurity elimination. Through rigorous screening with HPLC peaks from residual impurity and recovered drug as the criteria, a methanol concentration of 30% was chosen. The standard curve was linear （r2〉 0.999） over the range of 2-160 ng/mL with a limit of quantification （LOQ） of 2 ng/mL. Intra- and inter-day precision values were below 15%, and the accuracy ranged from -1.70% to 5.88% at all three quality control （QC） levels. The wavelength of maximum absorption was 238 nm, and a smaller LOQ value of 2 ng/mL was achieved compared with the reported method. The revised method was successfully applied in a pharmacokinetic study of Nimodipine in rats and sample preparations of lidocaine hydrochloride.