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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。
In this experiment, an improved method of extracting and purifying the target substance in plasma was established using nimodipine as a model drug and the method was applied to the pharmacokinetic study. The method took both the drug recovery rate and the impurity clearance rate . Pure methanol is first used to precipitate the plasma proteins in the sample, then the supernatant is concentrated to dryness. Residues were reconstituted with 10% to 100% methanol to investigate the effect of methanol concentration on drug recovery and impurity clearance. The peak intensity of impurities in the chromatogram and drug recovery as an indicator, found that 30% methanol as a reconstituted solvent can take both drug recovery and impurity clearance rate. The standard curve showed good linearity (r ~ 2≥0.999) with a LOQ of 2 ng / m L at a concentration range of 2-160 ng / mL. Under the three control levels of quality control samples, the intra- and inter-day precision were less than 15% and the accuracy was between -1.70% and 5.88%. Compared with the existing methods, the sample treated with this method can be detected at the maximum absorption wavelength of nimodipine 238 nm, the limit of quantification is reduced to 2 ng / m L. The improved method was successfully applied to pharmacokinetics of nimodipine in rats and sample processing of lidocaine hydrochloride.