用HPLC-MS/MS法检测多发性骨髓瘤患者血浆中来那度胺的浓度  

Determination of lenalidomide in the plasma of multiple myeloma patients by HPLC-MS/MS

作　　者：杨平 宋再伟 张现化[1,3] 周从亚 杨丽 景红梅[2] 赵荣生 YANG Ping;SONG Zai-wei;ZHANG Xian-hua;ZHOU Cong-ya;YANG Li;JING Hong-mei;ZHAO Rong-sheng(Department of Pharmacy,Peking University Third Hospital,Beijing 100191,China;Department of Hematology,Peking University Third Hospital,Beijing 100191,China;Therapeutic Drug Monitoring and Clinical Toxicology Center,Peking University,Beijing 100191,China)

机构地区：[1]北京大学第三医院,药剂科,北京100191 [2]北京大学第三医院,血液科,北京100191 [3]北京大学治疗药物监测和临床毒理中心,北京100191

出　　处：《中国临床药理学杂志》2023年第11期1622-1625,共4页The Chinese Journal of Clinical Pharmacology

基　　金：北京康盟慈善基金会医学科研发展基金项目临床与基础研究专项基金资助项目(TB211004)。

摘　　要：目的建立高效液相色谱-质谱(HPLC-MS/MS)法测定多发性骨髓瘤患者血浆中来那度胺的浓度。方法以13C 5-来那度胺为内标,血浆样本使用80%乙腈(含0.1%甲酸)沉淀蛋白。用Waters Atlantis^(■)HILIC silica色谱柱(5μm,2.1 mm×150.0 mm)进行分离,流动相为5 mmol·L^(-1)甲酸铵水溶液(0.1%甲酸)/乙腈(0.1%甲酸),梯度洗脱的方式,流速0.3 mL·min^(-1),柱温40℃,分析时间6 min。用电喷雾离子源(ESI),正离子模式,多反应监测(MRM)扫描方式。来那度胺监测分析离子对为m/z 260.1→149.1,内标监测离子对m/z 265.1→149.1。结果来那度胺在1~1000 ng·mL(-1)线性关系良好,相关系数>0.997,批内、批间精密度分别在11.5%和11.8%以内,批内、批间准确度分别为98.8%~108.9%和95.5%~105.0%。用本方法对33例临床患者的血浆浓度进行了检测分析。结论研究建立的方法可用于快速检测患者血浆中的来那度胺浓度,为该群体患者治疗药物监测和个体化治疗提供支持。Objective To establish an HPLC-MS/MS method for the determination of lenalidomide in plasma of multiple myeloma patients.Methods The 13 C 5-lenalidomide was taken as the internal standard(IS),plasma samples were precipitated with 80%acetonitrile(0.1%formic acid)before being injected into the HPLC-MS/MS system.Chromatographic separation was performed on a Waters Atlantis^(■)HILIC silica column(5μm,2.1 mm×150.0 mm)with a gradient mobile phase of ammonium formate(5 mmol·L^(-1),0.1%formic acid)-acetonitrile(containing 0.1%formic acid).The column temperature was set to 40℃,The flow rate of mobile phase was 0.3 mL·min^(-1) and the total run time was 6 min.Detection was performed in positive mode with an electrospray ionization(ESI)source.The multiple reaction monitoring(MRM)transitions were m/z 260.1→149.1 and m/z 265.1→149.1 for lenalidomide and the IS,respectively.Results The linear range was 1-1000 ng·mL^(-1)(r>0.997).Intra-and inter-run CV%were less than 11.5%and 11.8%,respectively.The intra-and inter-run accuracy was 98.8%-108.9%and 95.5%-105.0%,respectively.The method was applied to the quantification of lenalidomide in the plasma from 33 multiple myeloma patients.Conclusion The established method is fast and accurate for the quantification of lenalidomide in human plasma.It will support the therapeutic drug monitoring and individualized treatment of lenalidomide in clinical.

关 键 词：来那度胺 液相色谱-质谱 多发性骨髓瘤 治疗药物监测 

分 类 号：R979.1[医药卫生—药品]