大鼠血漿中厄他培南的HPLC法測定及初步藥動(dòng)學(xué)研究
發(fā)布時(shí)間:2018-02-21 01:29
本文關(guān)鍵詞: 厄他培南 碳青霉烯類 高效液相色譜 血藥濃度 藥代動(dòng)力學(xué) 大鼠標(biāo)準(zhǔn)血漿 出處:《藥物分析雜志》2017年11期 論文類型:期刊論文
【摘要】:目的:建立一種快捷、靈敏的高效液相色譜法測定大鼠血漿中的厄他培南,并考察其在大鼠體內(nèi)的藥動(dòng)學(xué)。方法:以甲硝唑?yàn)閮?nèi)標(biāo),血漿樣品經(jīng)過甲醇沉淀蛋白,離心,取上清液進(jìn)行HPLC分析。使用Diamonsil C_(18)(4.6 mm×150 mm,5.0μm)色譜柱,流動(dòng)相為乙腈-10 mmol·L~(-1)醋酸鈉溶液(11.4:88.6),流速1.0 m L·min~(-1),檢測波長295 nm,柱溫35℃,進(jìn)樣量10μL。結(jié)果:血漿中厄他培南濃度在2~200μg·m L~(-1)范圍內(nèi)線性關(guān)系良好(r=0.999 8);厄他培南的絕對(duì)回收率為(96.4±1.7)%~(99.3±1.2)%,方法回收率為(87.6±3.1)%~(107.9±2.5)%;內(nèi)標(biāo)甲硝唑的絕對(duì)回收率為(98.1±1.9)%;日內(nèi)、日間精密度均小于5%;中濃度的血漿樣品在常溫放置3 h、-40℃保存7 d及反復(fù)凍融3次,均能保持穩(wěn)定;稀釋效應(yīng)精密度為0.4%。大鼠靜脈注射厄他培南100 mg·kg~(-1)后的主要藥動(dòng)學(xué)參數(shù)分別為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)。結(jié)論:此HPLC法測定大鼠體內(nèi)厄他培南濃度,方法準(zhǔn)確快捷,靈敏度高,重復(fù)性好,適合該藥的藥動(dòng)學(xué)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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