脑脊液中利奈唑胺质量浓度测定方法的建立及临床应用

Establishment and clinical application of determination method of linezolid concentration in human cerebrospinal fluid

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 5TC-C18(2),250mm×4.6mm;流动相:甲醇-水(40∶60);流速:1.0mL·min^(-1);柱温:25℃;紫外检测波长:250nm。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=0.999 6),定量下限为0.31mg·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±1.11mg·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。

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 5TC-C18（2）（250mm×4.6mm）chromatographic column,mobile phase was consisted of methanol-water（40∶60）with a flow rate of 1.0mL·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 0.31mg·L^-1to 40mg·L^-1and the minimum quantitation limit was 0.31mg·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 concentration in the cerebrospinal fluid of intracranial infection patients was 2.67±1.11 mg·L^-1.Conclusion The method was simple,convenient,sensitive and accurate,it can be used for monitoring linezolid concentration of cerebrospinal fluid.The linezolid concentration in the cerebrospinal fluid varied in different patients.