目的 建立快速测定人血浆利奈唑胺浓度的高效液相色谱法,并用于重症感染者的治疗药物浓度监测.方法 色谱柱为ZORBAX-SB-C18 (4.6 mm×150 mm,5 μm),流动相为乙腈-水(22∶78),流速为1.1 mL·min-1,柱温为25 ℃,检测波长为254 nm,内标为氯霉素.用该方法 检测6例重症感染者静脉滴注600 mg利奈唑胺注射液后的血浆药物浓度,测得结果 与最低抑菌浓度(MIC)比较,为临床应用利奈唑胺提供指导.结果 利奈唑胺在0.25~20 mg·L-1内线性良好(r=0.999 2),最低定量限为250 μg·L-1.所测6例危重患者中,有2例患者出现利奈唑胺谷浓度小于最低抑菌浓度(2 mg·L-1)的情况.结论 该方法 准确可靠,操作简便,灵敏度高,可用于临床利奈唑胺血药浓度的检测,并能为制定个性化给药方案提供参考.%Objective To establish a rapid method for the determination of linezolid in human plasma by high performance liquid chromatography (HPLC) for the therapeutic drug monitoring in patients with severe infection.Methods Internal standard method (chloramphenicol) was adopted.Separation was performed on ZORBAX SB-C18 (4.6 mm×150 mm,5 μm) column.The mobile phase consisted of acetonitrile-water (22∶78) with a flow rate of 1.1 mL·min-1.The column temperature was 25 ℃ and the detection wavelength was 254 nm.The plasma concentrations were determined of 6 patients with severe infection who were under the treatment of intravenous infusion of 600 mg linezolid.The results were compared with minimum inhibitory concentration (MIC),which provided guidance for the clinical application of linezolid.Results The calibration curve was in good linear relationship (r=0.999 2) in the range of 0.25 to 20 mg·L-1,and the lowest limit of quantification was 250 μg·L-1.Two of the six patients with severe infections had a linezolid concentration below the minimum inhibitory concentration (2 mg·L-1).Conclusions The method is accurate,reliable,simple and sensitive.It can be used for the determination of plasma concentration of linezolid,providing a reference for the formulation of personalized dosing regimen.
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