A complex matrix characterization approach, applied to cigarette smoke, that integrates multiple analytical methods and compound identification strategies for non-targeted liquid chromatography with high-resolution mass spectrometry
A complex matrix characterization approach, applied to cigarette smoke, that integrates multiple analytical methods and compound identification strategies for non-targeted liquid chromatography with high-resolution mass spectrometry
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DOI：
10.1002/rcm.8571
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发表时间：
2020-01-30
影响因子：
2
通讯作者：
Bentley, Mark
中科院分区：
文献类型：
--
作者：
Arndt, Daniel;Wachsmuth, Christian;Bentley, Mark
为了表征复杂基质的化学组成，如含有6000多种成分的烟草烟雾，必须结合几种分析方法，以增加整个化学空间的化合物覆盖范围。此外，未知分子的鉴定需要在没有参考标准的情况下实施额外的确认工具，例如串联质谱光谱比较和质谱的计算机预测，这是一个主要的瓶颈。方法采用四种色谱/离子化技术的组合（正（+）和负（-）模式下的反相（RP）加热电喷雾电离（HESI），和亲水相互作用液相色谱（HILIC）- HESI阳性），使用Thermo Q Exactive（TM）液相色谱/高分辨率精确质谱法使用LC/HRAM-MS平台分析3R 4F衍生的烟雾。通过使用质谱库和来自多个集成数据库的计算机预测片段进行化合物鉴定。结果共鉴定出331种半定量估计值>= 100 ng/支的化合物，这些化合物分布在烟草烟雾的已知化学空间内。将多种基于LC/HRAM-MS的色谱/电离方法与互补化合物鉴定策略相结合，是最大限度地增加合格化合物数量和加强鉴定置信度水平的关键。总共有50种新的化合物被鉴定为存在于烟草烟雾中。在不存在参考MS 2光谱的情况下，计算机模拟MS 2光谱预测给出了化合物类别的良好指示，并用作我们的综合非靶向筛选（NTS）方法的额外确证工具。结论本研究提供了一种强有力的化学表征方法，已成功应用于卷烟烟气中新化合物的鉴定。我们相信，这种创新的方法具有普遍适用性和巨大的潜在利益的分析任何复杂的矩阵。
Rationale For the characterization of the chemical composition of complex matrices such as tobacco smoke, containing more than 6000 constituents, several analytical approaches have to be combined to increase compound coverage across the chemical space. Furthermore, the identification of unknown molecules requiring the implementation of additional confirmatory tools in the absence of reference standards, such as tandem mass spectrometry spectra comparisons and in silico prediction of mass spectra, is a major bottleneck. Methods We applied a combination of four chromatographic/ionization techniques (reversed-phase (RP) - heated electrospray ionization (HESI) in both positive (+) and negative (-) modes, RP - atmospheric pressure chemical ionization (APCI) in positive mode, and hydrophilic interaction liquid chromatography (HILIC) - HESI positive) using a Thermo Q Exactive (TM) liquid chromatography/high-resolution accurate mass spectrometry (LC/HRAM-MS) platform for the analysis of 3R4F-derived smoke. Compound identification was performed by using mass spectral libraries and in silico predicted fragments from multiple integrated databases. Results A total of 331 compounds with semi-quantitative estimates >= 100 ng per cigarette were identified, which were distributed within the known chemical space of tobacco smoke. The integration of multiple LC/HRAM-MS-based chromatographic/ionization approaches combined with complementary compound identification strategies was key for maximizing the number of amenable compounds and for strengthening the level of identification confidence. A total of 50 novel compounds were identified as being present in tobacco smoke. In the absence of reference MS2 spectra, in silico MS2 spectra prediction gave a good indication for compound class and was used as an additional confirmatory tool for our integrated non-targeted screening (NTS) approach. Conclusions This study presents a powerful chemical characterization approach that has been successfully applied for the identification of novel compounds in cigarette smoke. We believe that this innovative approach has general applicability and a huge potential benefit for the analysis of any complex matrices.