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-d3, 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.

中文翻译：

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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。

在这项工作中，一系列新的化学同位素标记试剂，名为左氧氟沙星酰肼的质量标签（LHMT），名为LHMT359 / 360/361/362/363/364/365/366/373/375/376/378/379 / 381最初被设计和合成用于高通量分析潜在的含己醛和庚烷的肺癌生物标志物。我们开发了左氧氟沙星-d3的新核心结构，大大增强了多路复用能力。其中，LHMT359用于标记标准化合物，作为定量的内标。以LHMT373-庚醛为虚拟模板，衍生化后制备了虚拟磁性分子印迹聚合物（DMMIPs），用于磁性分散固相萃取。建立了其他12种LHMT，用于高通量标记人血清样品中的己醛和庚醛。预先合成的DMMIP可以从均等混合的衍生化溶液中选择性提取己醛和庚醛的LHMTs衍生物。通过超高效液相色谱串联质谱（UHPLC-MS / MS）对己醛和庚醛的富集衍生物进行定量。一次UHPLC-MS / MS运行，仅在2分钟内即可同时从12个血清样品中定量己醛和庚醛。己醛和庚醛的检出限均为0.5 pM。人血清样品的准确性范围在-10.2％至+ 11.0％之间，日内和日间精度均低于11.3％。同时，该方法已成功应用于健康人和肺癌患者血清中己醛和庚醛的分析。结果表明，该方法具有灵敏度高，准确性高，选择性和分析通量。该方法的应用表明，所开发的方法在筛选疑似肺癌患者中很有希望。