13-Plex UHPLC-MS/MS Analysis of Hexanal and Heptanal Using Multiplex Tags Chemical Isotope Labeling Technology
13-Plex UHPLC-MS/MS Analysis of Hexanal and Heptanal Using Multiplex Tags Chemical Isotope Labeling Technology
复制标题
使用多重标签化学同位素标记技术对己醛和庚醛进行 13 重 UHPLC-MS/MS 分析
DOI：
10.1021/jasms.0c00222
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发表时间：
2020-09-02
影响因子：
3.2
通讯作者：
Liu, Huwei
中科院分区：
文献类型：
--
作者：
Hu, Jingwen;Chen, Shi-En;Liu, Huwei
本工作首次设计合成了一系列新的化学同位素标记试剂--基于左氧氟沙星酰肼的质量标签（LHMTs），命名为LHMT 359/360/361/362/363/364/365/366/373/375/376/378/379/381，用于高通量分析肺癌的潜在生物标志物己醛和庚醛。我们开发了一种新的核心结构的左氧氟沙星-d（3），这显着提高了多路复用能力。其中，LHMT 359用于标记标准化合物作为定量的内标。以LHMT 373-庚醛为虚拟模板，经衍生化制备了磁性分子印迹聚合物（DMMIPs）。建立了另外12个LHMT，用于高通量标记人血清样品中的己醛和庚醛。预合成的DMMIPs可以从均匀混合的衍生溶液中选择性地萃取己醛和庚醛的LHMT衍生物。通过超高效液相色谱串联质谱法（UHPLC-MS/MS）对己醛和庚醛的富集衍生物进行定量。一个单一的UHPLC-MS/MS运行，使同时定量己醛和庚醛从12个血清样品仅在2分钟内。己醛和庚醛的检测限均为0.5 pM。人血清样品的准确度范围为-10.2%至+11.0%，日内和日间精密度小于11.3%。同时，该方法成功地应用于健康人和肺癌患者血清样品中己醛和庚醛的分析。结果表明，该方法具有灵敏度高、准确度高、选择性好、分析通量高等优点。该方法的应用表明，该方法在肺癌疑似患者的筛查中具有良好的应用前景。
In this work, a new series of chemical isotope labeling reagents, levofloxacin-hydrazide-based mass tags (LHMTs) named as LHMT359/360/361/362/363/364/365/366/373/375/376/378/379/381 were first designed and synthesized for the high-throughput analysis of potential biomarkers containing hexanal and heptanal of lung cancer. We exploited a new core structure of levofloxacin-d(3), which significantly enhanced the multiplexing capability. Among them, LHMT359 was used for labeling standard compounds as internal standards for quantification. Using LHMT373-heptanal as dummy template, dummy magnetic molecularly imprinted polymers (DMMIPs) were prepared for magnetic dispersive solid-phase extraction after derivatization procedure. Other 12 LHMTs were established for high-throughput labeling hexanal and heptanal in human serum samples. The presynthesized DMMIPs can selectively extract LHMTs-derivatives of hexanal and heptanal from equally mixed derivatization solutions. The enriched derivatives of hexanal and heptanal were quantified by ultrahigh-performance liquid chromatography tandem mass spectrometry (UHPLC-MS/MS). A single UHPLC-MS/MS run enabled simultaneously quantifying hexanal and heptanal from 12 serum samples only within 2 min. The limits of detection were all 0.5 pM for hexanal and heptanal. The accuracies from human serum samples ranged from -10.2% to +11.0% with the intra- and interday precisions less than 11.3%. Meanwhile, this method was successfully applied for the analysis of hexanal and heptanal in serum samples from healthy people and lung cancer patients. The results show that this method has the significant advantages of high sensitivity, accuracy, selectivity, and analysis-throughput. The method application indicates that the developed method is promising in the screening of suspected lung cancer patients.