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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-Fu concentration in blood of patients, which is used in the determination of 5-Fu serum concentration. Methods: The mobile phase was eluted with an equal flow rate of 0.3 ml · min -1 on a Agela Innoval NH_2 column (2.1 mm × 50 mm, 5 μm) using methanol-ultrapure water (2:98) 40 ° C. Quantitative ion pairs of 5-Fu and the internal standard 5-bromouracil in negative ion electrospray ionization mode were m / z 128.8 → 42.1 and m / z 188.6 → 42.1 (internal standard 5-bromouracil), respectively. According to “biological sample quantitative analysis method validation guidelines (Chinese Pharmacopoeia 2015 four) ” to verify the method. Results: The linear range of 5-Fu was 10-1000 ng · ml -1 with a lower limit of quantitation of 10 ng · ml -1. Within the linear range of precision, accuracy, matrix effect, stability are in line with biological sample analysis requirements. Conclusion: The 5-Fu serum concentration test method established in this study is simple, rapid, accurate and reproducible. It can be used for 5-Fu blood concentration monitoring.