氟尿嘧啶血药浓度检测方法的建立及其临床应用  

Establishment of Plasma Concentration Detection Method for 5-Fluorouracil and its Clinical Application

作　　者：何光照[1,2] 薛宏波 杨全良 毕延智 雷凯[2] 张程亮[2] 

机构地区：[1]常州市肿瘤医院,江苏常州213032 [2]华中科技大学同济医学院附属同济医院药学部

出　　处：《中国药师》2017年第1期49-52,共4页China Pharmacist

基　　金：常州市卫生计生委重大科技项目(编号:ZD201514)

摘　　要：目的:建立测定患者氟尿嘧啶(5-Fu)血药浓度的液相色谱-串联质谱(LC-MS/MS)方法,验证后应用于临床5-Fu血药浓度测定。方法:使用Agela Innoval NH_2色谱柱(2.1 mm×50 mm,5μm),使用甲醇-超纯水(2∶98)为流动相等度洗脱,流速为0.3 ml·min^(-1),柱温为40℃。5-Fu和内标5-溴尿嘧啶在负离子电喷雾电离模式下的定量离子对分别为m/z 128.8→42.1和m/z188.6→42.1(内标5-溴尿嘧啶)。根据"生物样品定量分析方法验证指导原则(中国药典2015年版四部)"对该方法进行验证。结果:5-Fu浓度在10~1 000 ng·ml^(-1)范围内线性良好,定量下限为10 ng·ml^(-1)。在线性范围内精密度、准确度、基质效应、稳定性均符合生物样品分析的要求。结论:本研究建立的患者5-Fu血药浓度检测方法操作简便、快速、准确、重复性好,可用于5-Fu的血药浓度监测。Objective： To establish a liquid chromatography tandem mass spectrometry （LC-MS/MS） method for the determination of 5-fluorouracil （5-Fu） in patient＇ s plasma and apply it in clinics patients validation. Methods： 5-Fu was analyzed on an Agela Inno- val NH2（2.1 mm ×50 mm, 5 μm） column. Methanol： ultra pure water （2 ： 98） was used as the mobile phase with isocratic elution. The flow rate was 0.3 ml min-1 and the column temperature was set at 40 ℃. The ion transitions with electrospray ionization negative model were m/z 128.8→42.1 and m/z 188.6→2.1 for 5-Fu and 5- bromouracil （ the internal standard）, respectively. The LC-MS/ MS method was verified according to the guideline of quantitative analysis validation of biological samples （ Chinese Pharmacopoeia, 2015 edition, the fourth part）. Results： The calibration curve of 5-Fu was linear within the range of 10-1 000 ng ml-1. The lower limit of quantification was 10 ng ml-1. The precision, accuracy, matrix effect and stability within the linear range were all in line with the requirements of method validation. Conclusion： The LC-MS/MS method developed in the study for the determination of 5-Fu is simple, rapid, accurate and reproducible, which can be used for the plasma concentration detection of 5-Fu in patients.

关 键 词：氟尿嘧啶 液相色谱-串联质谱法 血药浓度 临床应用 

分 类 号：R969.1[医药卫生—药理学]