气相色谱-质谱联用技术用于尿样中β-阻断剂的初筛定量和确证

Screening,quantification and confirmation of β-blockers in urine using gas chromatography-mass spectrometry

建立了一种同时测定5种β-阻断剂（卡替洛尔、艾司洛尔、普萘洛尔、索他洛尔、比索洛尔）的气相色谱-质谱方法（GC-MS），并用于疑似阳性实际尿样的初筛、定量和确证。分别对游离态和结合态药物进行了提取，合并提取液后采用N-甲基-Ⅳ-三甲基硅基-三氟乙酰胺（C6H12F3NOSi，MSTFA）和N-甲基-双三氟乙酰胺试剂（C5H3F6NO2，MBTFA）进行混合衍生。确定了优化的GC—MS条件，建立了采用选择离子监测方式（SIM）初筛和全扫描方式（SCAN）确证的实验流程；建立了SIM模式下5种β-阻断剂的尿样加标工作曲线，其SIM方法的检出限达0．2—1．0ng／mL，尿样的加标回收率为70．5％～103．4％，相对标准偏差小于14．9％。该方法成功地用于普萘洛尔阳性尿样的检测．并绘制了普萘洛尔的尿代谢曲线。该方法对兴奋剂检测中β阻断剂滥用的控制有重要的意义。

A method was developed to perform the screening, quantification and confh-mation of the five β-blockers, propranolol, carteolol, bisoprolol, esmolol, and sotalol, in human urine using gas chromatography-mass spectrometry （GC-MS）. In sample preparation, conjugated and unconjugated t-blockers in urine were extracted separately, and the extracts were combined. The extracts were derivatized with N-methyl-N-trimethylsilyl-trifluoroacetamide （MSTFA） and N-methyl-bis（trifiuoroacetamide） （MBTFA）. The optimal conditions of GC-MS were established, and the progresses of screening by selected ion monitoring （SIM） mode and confirmation by full scan （SCAN） mode were completed. At last, the quantification curves of the five β-blockers in spiked urine were established by SIM mode. The limits of detection were 0. 2 - 1.0 ng/mL. Overall recoveries were 70. 5% - 103.4%, and the relative standard deviations were lower than 15%. In addition, the method was successfully applied to the analysis of the positive urine of propranolol, and the urinary excretion curve was also established accordingly. It is significant to prohibit the abuse of β-blockers in doping control.