高效液相色谱法测定人血浆中利奈唑胺浓度及临床监测

Determination of linezolid in human plasma by HPLC method and its application in the therapeutic drug monitoring in patients with severe infection

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-C_(18)(4.6 mm×150 mm,5μm),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250μg·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 chro-matography （HPLC ） for the therapeutic drug monitoring in patients with severe infection. Methods Internal standard method （ chlor-amphenicol ）was adopted. Separation was performed on ZORBAX SB-C18 （4. 6 mm × 150 mm,5 μm） column. The mobile phase consis-ted 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 concen-tration below the minimum inhibitory concentration （2 mg · L 1 ）. Conclusions The method is accurate, reliable, simple and sensi-tive. It can be used for the determination of plasma concentration of linezolid, providing a reference for the formulation of personalized dosing regimen.