反相高效液相色谱法测定美罗培南的血药浓度及其临床应用

目的建立快速测定人血浆中美罗培南的HPLC法,并用该法对临床使用美罗培南的患者进行血药浓度测定。方法采用蛋白沉淀法对血样进行预处理,以雷尼替丁为内标。色谱条件:Spursil ODS C18柱(250mm×4.6 mm,5μm);柱温:30℃;流动相:甲醇-乙腈混合有机相(10:3)-0.05 mol·L-1磷酸二氢钠缓冲液(15:85,缓冲盐pH=5.0);流速:0.8 mL·min-1;测定波长:298 nm。结果美罗培南的最低定量浓度为0.35μg·mL-1,线性范围为0.35¹81.17μg·mL-1,绝对回收率和相对回收率分别为95.4%和100.0%,日内、日间精密度均<10%。63名患者的血药峰浓度、谷浓度、t>MIC均具有较大差别。结论该方法快捷、经济、稳定、准确,适用于美罗培南临床血药浓度监测。临床患者美罗培南的谷峰浓度差异较大,对患者进行美罗培南峰谷浓度的测定对促进美罗培南在临床的合理应用具有重要意义。

Determination of meropenem in the plasma by RP-HPLC and its clinical application

Objective To establish an HPLC method to determine meropenem in the plasma. Methods The plasma samples were pretreated with protein precipitation. RP-HPLC was used with Spursil ODS C18 column（250 mm×4.6mm, 5 μm）. The mobile phase was acetonitrile-methanol（10 ：3, v/v）-0.05 mol·L- 1 sodium dihydrogen phosphate buffer = 15 ：85（v/v, pH = 5.0）. The detection wavelength was 298 nm and the fl ow rate was 0.8 mL·min- 1.Results The limit of quantitation was 0.35 μg·mL- 1. The calibration curve was linear at 0.35- 181.17 μg·mL-1.The absolute recovery and relative recovery were 95.4% and 100.0% respectively. The RSDs of intra-day and inter-day were lower than 10%. The Cmax, Cmin and tMIC of patients were considerably differfent. Conclusion The method is fast, stable, economic and accurate. It is suitable for the therapeutic drug monitoring and pharmacokinetic study of meropenem. Determination of meropenem concentrations in patients＇ plasma is necessary.