大鼠血浆中厄他培南的HPLC法测定及初步药动学研究

发布时间：2018-02-21 01:29

  本文关键词： 厄他培南 碳青霉烯类 高效液相色谱 血药浓度 药代动力学 大鼠标准血浆　出处：《药物分析杂志》2017年11期 　论文类型：期刊论文

【摘要】：目的:建立一种快捷、灵敏的高效液相色谱法测定大鼠血浆中的厄他培南,并考察其在大鼠体内的药动学。方法:以甲硝唑为内标,血浆样品经过甲醇沉淀蛋白,离心,取上清液进行HPLC分析。使用Diamonsil C_(18)(4.6 mm×150 mm,5.0μm)色谱柱,流动相为乙腈-10 mmol·L~(-1)醋酸钠溶液(11.4:88.6),流速1.0 m L·min~(-1),检测波长295 nm,柱温35℃,进样量10μL。结果:血浆中厄他培南浓度在2~200μg·m L~(-1)范围内线性关系良好(r=0.999 8);厄他培南的绝对回收率为(96.4±1.7)%~(99.3±1.2)%,方法回收率为(87.6±3.1)%~(107.9±2.5)%;内标甲硝唑的绝对回收率为(98.1±1.9)%;日内、日间精密度均小于5%;中浓度的血浆样品在常温放置3 h、-40℃保存7 d及反复冻融3次,均能保持稳定;稀释效应精密度为0.4%。大鼠静脉注射厄他培南100 mg·kg~(-1)后的主要药动学参数分别为AUC_(0→t)(207.9±19.7)μg·h·mL~(-1),AUC_(0→∞)(209.1±20.4)μg·h·mL~(-1),t_(1/2)(0.4±0.05)h,CL(0.48±0.05)L·(h·kg)~(-1),V(0.29±0.02)L·kg~(-1)。结论:此HPLC法测定大鼠体内厄他培南浓度,方法准确快捷,灵敏度高,重复性好,适合该药的药动学研究。
[Abstract]:Objective: to establish a rapid and sensitive HPLC method for the determination of etapenem in rat plasma and to investigate its pharmacokinetics in rats. Methods: Metronidazole was used as the internal standard and the plasma sample was precipitated by methanol and centrifuged. The supernatant was analyzed by HPLC. The chromatographic column consisted of Diamonsil CX 18mm 脳 150mm ~ (5.0 渭 m), the mobile phase was acetonitrile -10 mmol 路L ~ (-1) sodium acetate solution, the flow rate was 1.0 mL 路min ~ (-1) N ~ (-1), the detection wavelength was 295 nm, the column temperature was 35 鈩，

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