重症患者应用美罗培南的血药浓度监测方法优化及临床应用实例

Optimization of the concentration monitoring method of meropenem in critically ill patients and its clinical application

目的:建立超高效液相色谱-串联质谱(UPLC-MS/MS)法监测重症患者美罗培南血药浓度。方法:以法罗培南为内标,用蛋白沉淀前处理方法。色谱柱为AQ C18(100mm×2.1mm,3μm),流动相为乙腈-0.2%甲酸水溶液(梯度洗脱),流速为0.4mL·min^(-1),正离子模式多反应监测(MRM)扫描分析,并考察专属性、标准曲线与定量下限、精密度与回收率、基质效应和稳定性。测定6例使用美罗培南的重症患者血药峰、谷浓度;以%T>MIC作为PK/PD靶目标评估计给药方案。结果:血浆中美罗培南线性范围为0.1~40μg·mL^(-1)(r=0.999),定量下限为0.1μg·mL^(-1),低、中、高浓度的美罗培南提取回收率相一致,日内、日间精密度相对标准偏差(RSD)均小于15%。结论:本方法操作简便快速,特异性强,灵敏度高,可用于临床美罗培南血药浓度的测定及临床美罗培南个体化用药指导。

OBJECTIVE To establish the UPLC-MS/MS method for the determination of meropenem in plasma of critically ill patients.METHODS The plasma procedure involved a single-step protein precipitation by acetonitrile.The samples were separated by a AQ C18 column（100 mm×2.1 mm,3μm）using a mobile phase consisted of acetonitrile-0.2% formic acid（gradient elution）at a flow rate of 0.4 mL·min-1.The protonated ions of analytes were detected in positive ionization in multiple reaction monitoring mode（MRM）.The specificity,standard curve,lower limit of quantitation,precision,recovery rate and stability as well as the matrix effect were investigated.The method was applied in the determination of the peak and trough plasma meropenem concentrations from 6 critically ill patients who took meropenem.The dosage regimens were evaluated with%TMICas the PK/PD target.RESULTS The calibration curve was linear over a concentration range of 0.1 to 40μg·mL^-1（r=0.999）and the lower limit of quantitation was 0.1μg·mL^-1.The recovery rates of low,medium,high concentrations of meropenem were consistent,the intra-day and inter-day RSD were both lower than 15%.CONCLUSION The method is simple and quick,with high specificity and sensitivity.Therefore it is suitable for the detection of meropenem in the human plasma,and also can be applicable to the guidance for individualized meropenem use in clinical practice.