应用UPLC研究亚胺培南在大鼠体内的药动学

    A Simple UPLC Method for Determination of Imipenem in Rat Plasma and Its Application in Pharmacokinetic Study

    • 摘要: 目的 建立灵敏的超高效液相色谱法测定大鼠血浆中亚胺培南的浓度。 方法 血浆样品采用乙腈蛋白沉淀方法,色谱柱为Dikma Diamonsil C18;以0.1 mol·L-1磷酸氢二钠(85%磷酸调pH至7.0)-甲醇(45∶55)为流动相;流速为1.0 mL·minL-1;柱温为35 ℃;检测波长为295 nm。 结果 亚胺培南血药浓度在0.5~100 μg·mL-1内线性关系良好(r=0.999 7),最低检测限为0.5 μg·mL-1;日内、日间RSD均≤10%,提取回收率在80.5%~81.2%之间。6只SD大鼠单剂量口服给予亚胺培南后药动学参数分别为:Cmax(75.3±6.2)μg·mL-1t1/2(6.72±1.58)h;AUC0-t(694.1±28.3)h·μg·mLL-1;AUC0-∞(746.2±32.9) h·μg·mL-1结论 本方法简便、准确、灵敏、专属性强,同样适用于人血浆中亚胺培南浓度的测定及其药动学研究,对于评价亚胺培南疗效和安全性有重要意义。

       

      Abstract: OBJECTIVE The purpose of this study was to develop a simple and sensitive UPLC method to quantify imipenem in plasma. METHODS The chromatographic separation was carried out on a Dikma Diamonsil C18 column with a mobile phase consisting of 0.1M Na2HPO4 (85%H3PO4 adjust to pH 7.0)-methonal (45∶55) at a flow rate of 1.0 mL·min-1. The temperature of column was 35 ℃. UV wavelength mode was used, with imipenem monitored at 295 nm. RESULTS The calibration was linear in the range of 0.5-100 μg·mL-1 for imipenem. Inter- and intra-day precision were less than 10% for imipenem, respectively. The recovery was 80.5%-81.2%. The pharmacokinetic parameters were: Cmax (75.3±6.2)μg·mL-1; t1/2 (6.72±1.58)h; AUC0-t (694.1±28.3)h·μg·mL-1; AUC0-∞(746.2±32.9)h·μg·mL-1. CONCLUSION This simple, sensitive, accurate and cost-effective method can be used in routine clinical practice to monitor imipenem concentrations in plasma for patients.

       

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