LC-MS/MS测定老年重症感染患者血浆中利奈唑胺浓度

Determination of linezolid in critically ill patients plasma by LC-MS/MS

关键词:  利奈唑胺  液质联用法  血药浓度

Key words:  linezolid  LC-MS/MS  plasma drug concentration

摘要:

目的 采用LC-MS/MS测定重症感染患者血浆中利奈唑胺的浓度，并进行血药浓度监测。方法 血浆样品用乙腈沉淀蛋白后，以D3-利奈唑胺为内标，选用ZORBAX SB C₁₈色谱柱（2.1 mm×100 mm，3.5 μm），以乙腈-水（均含0.1%甲酸）为流动相，梯度洗脱，梯度流速恒定为0.30 mL·min^-1，柱温为30℃，进样量5 μL，总分析时间为4.0 min，采用电喷雾离子化源，负离子方式，多反应监测扫描方式进行监测。结果 血浆中利奈唑胺浓度线性范围为0.10~20.0 μg·mL^-1（r>0.99），定量下限为0.10 μg·mL^-1；质控样品回收率为93.3%~106.7%；日内、日间RSD均<15%；提取回收率为74.9%~85.1%。结论 该方法快速、灵敏、准确，专属性强，重复性好，适用于利奈唑胺临床血药浓度测定。

Abstract:

OBJECTIVE To develop an LC-MS/MS method for determination of linezolid in critically ill patients plasma and applied to drug monitoring. METHODS The plasma samples were precipitated with acetonitrile, with D3-linezolid as an internal standard. The separation was achieved on ZORBAX SB C₁₈column (2.1 mm×100 mm, 3.5 μm) and eluted with linear gradient using acetonitrile and water (both of containing 0.1% formic acid) at the flow rate of 0.30 mL·min^-1, the injection volume was 5 μL and the column temperature was 30℃. The total time of the analysis was 4.0 min. Detection of the analytes were achieved using positive ion electrospray ionization (ESI) in the multiple reaction monitoring (MRM) mode. RESULTS The linear calibration curve of linezolid obtained concentration range of 0.10-20.0 mg·mL^-1(r>0.99), with the lower limit of quantitation of 0.10 mg·mL^-1. The accuracy of linezolid was within 93.3%-106.7%, intra-day and inter-day relative standard deviations were both <15%. The extraction recoveries ranged 74.9%-85.1%. CONCLUSION The established method is rapid, sensitive, accurate, specific and reliable, and suitable for the study of therapeutic drug monitoring of linezolid.