用UPLC-MS/MS法测定人脑脊液中康替唑胺浓度  

Determination of contezolid in human cerebro spinal fluid by UPLC-MS/MS

作　　者：贠菊平 王梓贺 王文静[2] 刘炜 YUN Ju-ping;WANG Zi-he;WANG Wen-jing;LIU Wei(Department of Pharmacy,Beijing You'an Hospital,Capital Medical University,Beijing 100069,China;ClinicaLl aboratory Center,Beijing You'an Hospital,Capital Medical University,Beijing 100069,China)

机构地区：[1]首都医科大学附属北京佑安医院药学部,北京100069 [2]首都医科大学附属北京佑安医院临检中心,北京100069

出　　处：《中国临床药理学杂志》2025年第1期91-95,共5页The Chinese Journal of Clinical Pharmacology

基　　金：首都医科大学北京佑安医院研究型病房示范建设基金资助项目(2-1-1-2n-03-10-03)。

摘　　要：目的建立超高效液相色谱-串联质谱(UPLC-MS/MS)法测定人脑脊液中康替唑胺浓度的方法。方法以利奈唑胺为内标(IS),乙腈为蛋白沉淀剂。用Waters ACQUITY UPLC■BEH C_(18)(2.1 mm×50.0mm,1.7μm)色谱柱进行分离,流动相为0.1%甲酸水溶液-0.1%甲酸乙腈溶液,梯度洗脱方式,流速为0.4mL·min^(-1),柱温为40℃,自动进样器温度为10℃,分析时间为4min。用电喷雾离子源,正离子模式,多反应监测扫描方式。康替唑胺监测分析离子对为m/z409.15→269.14,利奈唑胺监测离子对为m/z338.14→195.10。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、残留效应、稀释效应及稳定性。结果脑脊液中内源性物质对待测物利奈唑胺及内标物利奈唑胺的测定均无干扰,方法专属性好。康替唑胺在20~5000ng·mL^(-1)内线性关系良好,标准曲线为y=8.97×10^(-4)x+1.95×10^(-2)(r=0.9991),定量下限为20ng·mL^(-1)。批内、批间精密度相对标准偏差(RSD)均<15%,提取回收率为90.96%~98.71%。质控脑脊液样本的平均内标归一化基质效应因子为94.39%~100.25%。稀释效应的RSD均<15%。康替唑胺脑脊液样本在室温及自动进样器内72h、-20℃和-80℃储存90d、反复冻融3次均稳定,RSD均<10%。结论本方法灵敏度高、快速、简便、准确,适用于人脑脊液中康替唑胺治疗浓度监测。Objective To establish a method for determining the concentration of contezolid in human cerebro spinal fluid(CSF)using ultra high performance liquid chromatography tandem mass spectrometry(UPLC-MS/MS).Methods Linezolid as the internal standard(IS)and acetonitrile as the protein precipitant.Waters ACQUITY UPLC■BEH C_(18)(2.1 mm×50.0 mm,1.7μm)chromatographic column was used for separation,with a mobile phase of 0.1% formic acid aqueous solution -0.1% formic acid acetonitrile solution,gradient elution method,flow rate was 0.4 mL·min^(-1),column temperature was 40℃,automatic sampler temperature was 10℃,the analysis time was 4 minutes.Electrospray ion source,positive ion mode,and multi reaction monitoring scanning mode were used.The monitoring and analysis ion pairs for contezolid were m/z 409.15→269.14,and the monitoring ion pairs for linezolid were m/z 338.14→195.10.The specificity,standard curve and lower limit of quantification(LLOQ),precision and recovery rate,matrix effect,residual effect,dilution effect and stability of the method were investigated.Results The endogenous substances in CSF do not interfere with the determination of the analyte contezolid and the internal standard linezolid,and the method has good specificity.Satisfactory linearity was observed within the concentration range of 20-5000 ng·mL^(-1) for contezolid in CSF,the calibration curve was y=8.97×10^(-4)x+1.95×10^(-2)(r=0.9991),and the LLOQ was 20 ng·mL^(-1).Precision of the intra-batch and inter-batch relative standard deviation(RSD)<15%,and the extraction recovery were 90.96%-98.71%.The average normalized matrix effect factor of the quality control CSF sample were 94.39%-100.25%.The RSD of dilution effect<15%.The CSF samples of contezolid were stored at room temperature,in the automatic sampler for 72 hours,-20℃ and -80℃ for 90 days,and subjected to repeated freezing and thawing three times,were stable with all of which the RSD<10%.Conclusion This method is high sensitivity,rapid,simple and accurate,which is very suita

关 键 词：康替唑胺 脑脊液 超高效液相色谱-串联质谱法 治疗药物监测 

分 类 号：R978.1[医药卫生—药品]