柱前衍生化HPLC用于顺铂纳米粒大鼠药动学的研究

发布时间：2018-03-01 21:23

  本文关键词： 顺铂 柱前衍生化 高效液相色谱法 二乙基二硫代氨基甲酸钠 纳米粒 药动学　出处：《沈阳药科大学学报》2017年02期 　论文类型：期刊论文

【摘要】：目的建立一种改良的柱前衍生化-高效液相色谱法(HPLC)测定顺铂纳米粒大鼠血浆药物浓度,并将其应用于大鼠体内药动学研究。方法采用衍生化试剂二乙基二硫代氨基甲酸钠(DDTC)与顺铂络合生成Pt(DDTC)2衍生化产物,加入内标物地西泮,氯仿提取,挥干,乙酸乙酯复溶,采用HPLC法测定。色谱条件:色谱柱为C18,流动相为水-甲醇(体积比为1∶3),检测波长为252 nm。大鼠以7.5 mg·kg-1剂量分别尾静脉注射顺铂纳米粒和注射剂,不同时间取血,采用所建立的分析方法测定血浆顺铂质量浓度,计算药动学参数。结果本法可精密准确地测定顺铂纳米粒静脉注射给药后大鼠血浆中的顺铂质量浓度,线性范围为0.488~97.6 mg·L~(-1),最低定量限为100μg·L~(-1),日内、日间变异系数均5%。顺铂纳米粒的主要药动学参数:ρmax为(62.85±13.83)mg·L~(-1),t1/2为(3.53±1.57)min,AUC0-∞为(176.81±46.19)mg·L~(-1)·h,CL为(44.89±11.91)m L·kg·h-1。结论该方法适用于顺铂纳米粒体内药物质量浓度测定及其药动学的研究。与顺铂注射液相比,顺铂纳米粒药时曲线下面积显著提高,清除率显著降低,其药动学的改变有利于降低药物的毒副作用。
[Abstract]:Objective to establish a modified precolumn derivatization and high performance liquid chromatography (HPLC) method for the determination of plasma drug concentration in cisplatin nanoparticles in rats. Methods Pt(DDTC)2 derivatives were synthesized by complexation of diethyldithiocarbamate sodium diethyldithiocarbamate with cisplatin. Diazepam was added, chloroform was extracted, dried, ethyl acetate was redissolved. HPLC method was used. The chromatographic conditions were as follows: the column was C18, the mobile phase was water-methanol (volume ratio 1: 3), the detection wavelength was 252nm.Cisplatin nanoparticles and injection were injected into rat tail vein at a dose of 7.5 mg 路kg-1, and blood was collected at different time. The established analytical method was used to determine the mass concentration of cisplatin in plasma and to calculate the pharmacokinetic parameters. Results this method can accurately and accurately determine the mass concentration of cisplatin in plasma of rats after intravenous injection of cisplatin nanoparticles. The linear range was 0.488g 路L ~ (-1) mg 路L ~ (-1), and the lowest limit of quantification was 100 渭 g 路L ~ (-1). The main pharmacokinetic parameters of cisplatin nanoparticles were: 蟻 max = 62.85 卤13.83 mg 路L ~ (-1) 路L ~ (-1 / 2) = 3.53 卤1.57 min ~ (-1) AUC0- 鈭，

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