Liquid chromatography–Mass Spectrometry (LC–MS) has been widely used in natural product analysis. Global detection and identification of nontargeted components are desirable in natural product research, for example, in quality control of Chinese herbal medicine. Nontargeted components analysis continues to expand to exciting life science application domains such as metabonomics. With this background, the present review summarizes recent developments in the analysis of minor unknown natural products using LC–MS and mainly focuses on the determination of the molecular formulae, selection of precursor ions, and characteristic fragmentation patterns of the known compounds. This review consists of three parts. Firstly, the methods used to determine unique molecular formula of unknown compounds such as accurate mass measurements, MSⁿ spectra, or relative isotopic abundance information, are introduced. Secondly, the methods improving signal‐to‐noise ratio of MS/MS spectra by manual‐MS/MS or workflow targeting‐only signals were elucidated; pure precursor ions can be selected by changing the precursor ion isolated window. Lastly, characteristic fragmentation patterns such as Retro‐Diels–Alder (RDA), McLafferty rearrangements, “internal residue loss,” and so on, occurring in the molecular ions of natural products are summarized. Classical application of characteristic fragmentation patterns in identifying unknown compounds in extracts and relevant fragmentation mechanisms are presented (RDA reactions occurring readily in the molecular ions of flavanones or isoflavanones, McLafferty‐type fragmentation reactions of some natural products such as epipolythiodioxopiperazines; fragmentation by “internal residue loss” possibly involving ion–neutral complex intermediates). © 2016 Wiley Periodicals, Inc. Mass Spec Rev 37:202–216, 2018.

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基于特征碎片信息的LC-MS分析未知未知天然小产物的最新进展（2000-2015）

液相色谱-质谱法（LC-MS）已广泛用于天然产物分析中。在天然产物研究中，例如在中草药的质量控制中，需要对非靶向成分进行全球检测和鉴定。非目标成分分析继续扩展到令人兴奋的生命科学应用领域，例如代谢组学。在此背景下，本综述总结了使用LC-MS分析微量未知天然产物的最新进展，主要侧重于分子式的确定，前体离子的选择以及已知化合物的特征性片段化模式。这篇综述由三部分组成。首先，用于确定未知化合物的独特分子式的方法，例如精确的质量测量，MS^ñ引入光谱或相对同位素丰度信息。其次，阐明了通过手动MS / MS或仅针对工作流的信号来提高MS / MS光谱信噪比的方法。可以通过更改前体离子隔离窗口来选择纯前体离子。最后，总结了天然产物分子离子中发生的特征性片段化模式，例如Retro-Diels-Alder（RDA），McLafferty重排，“内部残留物损失”等。提出了特征性断裂模式在鉴定提取物中未知化合物和相关断裂机理方面的经典应用（RDA反应在黄烷酮或异黄酮的分子离子中容易发生，某些天然产物如表聚硫代二氧杂哌嗪的McLafferty型断裂反应；因“内部残留物损失”而碎裂，可能涉及离子中和的复杂中间体。©2016 Wiley Periodicals，Inc.质谱修订37：202–216，2018年。