液相色谱-串联质谱法同时测定人全血中4种免疫抑制剂药物浓度  

Simultaneous Determination of Four Immunosuppressants Concentrations in Human Whole Blood by LC-MS/MS

作　　者：贾永娟 刘杏立 刘春冉 倪君君 JIA Yongjuan;LIU Xingli;LIU Chunran;NI Junjun(Beijing Harmony Health Medical Diagnostics Co.,Ltd.,Beijing 100011)

机构地区：[1]北京和合医学诊断技术股份有限公司,北京100011

出　　处：《分析科学学报》2024年第1期70-74,共5页Journal of Analytical Science

摘　　要：建立了液相色谱-串联质谱同时测定人全血中他克莫司、雷帕霉素、环孢素A与霉酚酸4种免疫抑制剂药物浓度的检测方法。全血样品经蛋白沉淀后,通过Waters XBridge C18色谱柱(100 mm×2.1 mm,5μm),以甲醇-水(含0.1%甲酸和5 mmol/L乙酸铵)为流动相梯度洗脱,采用电喷雾电离源,正离子化多反应监测模式定量检测。结果表明,4种免疫抑制剂在各自检测浓度范围内线性良好,相关系数均大于0.99。基质效应相对标准偏差(RSD)在9.4%以内。加标回收率在94.2%~104.3%之间,日内日间精密度RSD<5.49%。参加英国Laboratory of the Government Chemist(LGC)室间质评的偏差均在12.50%以内,正确度良好。该方法操作简单、准确度好、灵敏度高,适用于血液中免疫抑制剂治疗药物浓度监测。In this work,a fast method for simultaneous determination of tacrolimus,rapamycin,ciclosporin A and mycophenolic acid in human whole blood by liquid chromatography-tandem mass spectrometry was established.After protein precipitation of the whole blood samples,a Waters XBridge C18 column(100 mm×2.1 mm,5 μm) was used for the separation of the four immunosuppressants with methanol-water(containing 0.1% formic acid and 5 mmol/L ammonium acetate).Target analytes were then detected by positive electrospray ionization mode and multiple reaction monitoring mode for quantitative analysis.Under the optimum conditions,the four immunosuppressants were determined within 3.5 min.Good linearity for all analytes over the studied concentration range was achieved with correlation coefficient higher than 0.99.The relative standard deviation(RSD) of matrix effect was within 9.4%.The recoveries for all analytes at three spiked levels ranged from 94.2% to 104.3%,with the intra-day and inter-day precision RSD less than 5.49%.The accuracy of the method was verified by Laboratory of the Government Chemist(LGC) external quality assessment,and the biases were all within 12.50%,indicating good accuracy.The method is simple,accurate and sensitive,and is suitable for monitoring the concentration of immunosuppressive drugs in blood,providing a reference for clinical therapeutic drug monitoring of immunosuppressants.

关 键 词：他克莫司 雷帕霉素 环孢素A 霉酚酸 液相色谱串联质谱法 

分 类 号：O657.63[理学—分析化学] R917[理学—化学]