脑脊液中利奈唑胺质量浓度测定方法的建立及临床应用

摘要

Objective To establish a method for the determination of linezolid concentration in human cerebrospinal fluid and apply this method to determine linezolid concentration in cerebrospinal fluid of intracranial infection patients.Methods Reversed phase high-performance liquid chromatography was selected and external standard method was used.The separation was performed on an Agilent 5 TC-C1 8 (2)(250 mm×4.6 mm)chromatographic column,mobile phase was consisted of methanol-water (40∶60)with a flow rate of 1.0 mL·min-1 .The column temperature was 25 ℃ and the UV detection wavelength was 250 nm.The linezolid concentration was detected in the cerebrospinal fluid of intracranial infection patients.Results The calibration curve of linezolid showed good linearity (r=0.999 6)in the drug level range from 0.31 mg·L-1 to 40 mg·L-1 and the minimum quantitation limit was 0.31 mg·L-1 .The absolute recovery and the relative recovery rate were above 85% and the intra-day and inter-day variation was below 5%.Meropenem,ceftriaxone and ceftazidime had no influence in the determination of linezolid.The linezolid concentra-tion in the cerebrospinal fluid of intracranial infection patients was 2.67±1.1 1 mg·L-1 .Conclusion The method was simple,con-venient,sensitive and accurate,it can be used for monitoring linezolid concentration of cerebrospinal fluid.The linezolid concentra-tion in the cerebrospinal fluid varied in different patients.%目的：建立人脑脊液中利奈唑胺质量浓度测定方法并开展临床检测。方法使用高效液相色谱仪(HPLC),采用外标法。色谱条件为：色谱柱：Agilent 5 TC-C18(2),250 mm×4.6 mm；流动相：甲醇-水(40∶60)；流速：1.0 mL·min-1；柱温：25℃；紫外检测波长：250 nm。结果利奈唑胺质量浓度在0.31~40 mg· L-1范围内线性关系良好(r =0.9996),定量下限为0.31 mg·L-1,方法回收率、提取回收率均大于85%,高、中、低3个质量浓度日内、日间精密度的 RSD 值均小于5%。药物干扰试验中美罗培南、头孢曲松及头孢他啶对利奈唑胺的测定无影响。对8例患者开展27例次脑脊液利奈唑胺质量浓度测定,平均质量浓度为2.67±1.11 mg·L-1。结论建立的利奈唑胺脑脊液质量浓度测定方法简单、方便、灵敏、准确,可用于临床检测；利奈唑胺在脑脊液中的质量浓度个体差异较大。