本文關(guān)鍵詞： 順鉑 柱前衍生化 高效液相色譜法 二乙基二硫代氨基甲酸鈉 納米粒 藥動(dòng)學(xué)　出處：《沈陽(yáng)藥科大學(xué)學(xué)報(bào)》2017年02期 　論文類型：期刊論文

【摘要】：目的建立一種改良的柱前衍生化-高效液相色譜法(HPLC)測(cè)定順鉑納米粒大鼠血漿藥物濃度,并將其應(yīng)用于大鼠體內(nèi)藥動(dòng)學(xué)研究。方法采用衍生化試劑二乙基二硫代氨基甲酸鈉(DDTC)與順鉑絡(luò)合生成Pt(DDTC)2衍生化產(chǎn)物,加入內(nèi)標(biāo)物地西泮,氯仿提取,揮干,乙酸乙酯復(fù)溶,采用HPLC法測(cè)定。色譜條件:色譜柱為C18,流動(dòng)相為水-甲醇(體積比為1∶3),檢測(cè)波長(zhǎng)為252 nm。大鼠以7.5 mg·kg-1劑量分別尾靜脈注射順鉑納米粒和注射劑,不同時(shí)間取血,采用所建立的分析方法測(cè)定血漿順鉑質(zhì)量濃度,計(jì)算藥動(dòng)學(xué)參數(shù)。結(jié)果本法可精密準(zhǔn)確地測(cè)定順鉑納米粒靜脈注射給藥后大鼠血漿中的順鉑質(zhì)量濃度,線性范圍為0.488~97.6 mg·L~(-1),最低定量限為100μg·L~(-1),日內(nèi)、日間變異系數(shù)均5%。順鉑納米粒的主要藥動(dòng)學(xué)參數(shù):ρmax為(62.85±13.83)mg·L~(-1),t1/2為(3.53±1.57)min,AUC0-∞為(176.81±46.19)mg·L~(-1)·h,CL為(44.89±11.91)m L·kg·h-1。結(jié)論該方法適用于順鉑納米粒體內(nèi)藥物質(zhì)量濃度測(cè)定及其藥動(dòng)學(xué)的研究。與順鉑注射液相比,順鉑納米粒藥時(shí)曲線下面積顯著提高,清除率顯著降低,其藥動(dòng)學(xué)的改變有利于降低藥物的毒副作用。
[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 鹵13.83 mg 路L ~ (-1) 路L ~ (-1 / 2) = 3.53 鹵1.57 min ~ (-1) AUC0- 鈭，

本文編號(hào)：1553612