用二维液相色谱法测定人血清中利奈唑胺浓度及其临床应用  

Determination of linezolid concentration in human serum by two-dimensional liquid chromatography and its clinical application

作　　者：韩文超 丁建强 张寒娟[1] 陈永妍[1] 王高彪 丁蕊 袁冬冬[1] HAN Wen-chao;DING Jian-qiang;ZHANG Han-juan;CHEN Yong-yan;WANG Gao-biao;DING Rui;YUAN Dong-dong(Department of Pharmacy,The 7th People’s Hospital of Zhengzhou,Zhengzhou 450016,Henan Province,China;Department of Pharmacy,Armed Police Corps Hospital of Henan,Zhengzhou 450052,Henan Province,China)

机构地区：[1]郑州市第七人民医院药学部,河南郑州450016 [2]武警河南省总队医院药学部,河南郑州450052

出　　处：《中国临床药理学杂志》2023年第7期1033-1036,共4页The Chinese Journal of Clinical Pharmacology

基　　金：中国成年肾移植受者霉酚酸药动学研究基金资助项目(LHGJ20200732)。

摘　　要：目的 建立利奈唑胺血药浓度的分析方法,以指导临床合理用药。方法 基于新型二维液相色谱仪建立利奈唑胺血药浓度的测定方法。一维色谱柱:Aston SNCB(50.0 mm×4.6 mm, 5μm),二维色谱柱:Aston SCB(250.0 mm×4.6 mm, 5μm),流速:1.0 mL·min^(-1),柱温:40℃,紫外检测波长:254 nm,进样量:200μL。考察该方法的专属性、标准曲线与定量下限、精密度与回收率、基质效应及稳定性,并将该方法应用于临床患者利奈唑胺的血药浓度监测。结果 血浆中利奈唑胺的标准曲线方程为y=-357.10+9.69×10^(4)x(R^(2)=0.999 8),在0.19~20.11μg·mL^(-1)内呈良好的线性关系,定量下限为0.19μg·mL^(-1);低、中、高3个质量浓度的相对回收率在96.60%~103.37%,日内和日间精密度均低于5%,说明本方法检测性能良好。采集20例使用利奈唑胺患者血清样本,检测结果显示不在治疗窗的患者占总数的60%。结论 本方法简便快捷,准确高效,实现了自动化分析,适用于临床血药浓度高通量分析监测;使用利奈唑胺的患者个体差异较大,个体化治疗时需要进行血药浓度监测。Objective To establish a blood drug concentration analysis method for linezolid to guide the clinical rational use of drugs.Methods In this study,a new two-dimensional liquid chromatograph was used to establish a method for the determination of blood concentration of linezolid.One-dimensional column Aston SNCB(50.0 mm×4.6 mm,5μm),two-dimensional column Aston SCB(250.0 mm×4.6 mm,5μm),flow rate:1.0 mL·min^(-1),column temperature:at 40℃.The UV detection wavelength was 254 nm and the sample size was 200μL.After verifying the selectivity,standard curve and lower limit of quantification,precision and recovery,matrix effect and stability of the method,it was applied to the blood concentration monitoring of linezolid in clinical patients.Results The standard curve equation of linezolid in plasma was y=-357.10+9.69×10^(4)x(R^(2)=0.9998),which showed a good linear relationship in the range of 0.19-20.11μg·mL^(-1),and the lower limit of quantification was 0.19μg·mL^(-1);the relative recoveries of the low,medium and high concentrations were in the range of 96.60%-103.37%,and the intra-day and inter-day precisions were lower than 5%,indicating that the detection performance of this method was good. Serum samples were collected from 20 patients using linezolid,and the test results showed that 60%of the patients were not in the treatment window. Conclusion The method is simple,fast,accurate and efficient,itrealizes automatic analysis,and is suitable for high - throughput analysis and monitoring of clinical blood drugconcentration;individual differences in patients using linezolid are large,and blood drug concentration monitoring isrequired during individualized treatment.

关 键 词：二维液相色谱 利奈唑胺 治疗药物监测 

分 类 号：R978.1[医药卫生—药品]