Lipids, serving as the structural components of cellular membranes, energy storage, and signaling molecules, play the essential and multiple roles in biological functions of mammals. Mass spectrometry (MS) is widely accepted as the first choice for lipid analysis, offering good performance in sensitivity, accuracy, and structural characterization. However, the untargeted qualitative profiling and absolute quantitation of lipids are still challenged by great structural diversity and high structural similarity. In recent decade, chemical derivatization mainly targeting carboxyl group and carbon-carbon double bond of lipids have been developed for lipidomic analysis with diverse advantages: (i) offering more characteristic structural information; (ii) improving the analytical performance, including chromatographic separation and MS sensitivity; (iii) providing one-to-one chemical isotope labeling internal standards based on the isotope derivatization regent in quantitative analysis. Moreover, the chemical derivatization strategy has shown great potential in combination with ion mobility mass spectrometry and ambient mass spectrometry. Herein, we summarized the current states and advances in chemical derivatization-assisted MS techniques for lipidomic analysis, and their strengths and challenges are also given. In summary, the chemical derivatization-based lipidomic approach has become a promising and reliable technique for the analysis of lipidome in complex biological samples.

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基于质谱的脂质组学的化学衍生化策略

脂质作为细胞膜、能量储存和信号分子的结构成分，在哺乳动物的生物学功能中发挥着重要的多重作用。质谱 (MS) 被广泛接受为脂质分析的首选，在灵敏度、准确性和结构表征方面具有良好的性能。然而，脂质的非靶向定性分析和绝对定量仍然面临巨大的结构多样性和高度结构相似性的挑战。近十年来，主要针对脂质的羧基和碳碳双键的化学衍生化已被开发用于脂质组学分析，具有多种优势：（i）提供更多特征结构信息；(ii) 改进分析性能，包括色谱分离和 MS 灵敏度；(iii) 在定量分析中提供基于同位素衍生试剂的一对一化学同位素标记内标。此外，化学衍生化策略与离子淌度质谱和环境质谱相结合显示出巨大的潜力。在此，我们总结了用于脂质组学分析的化学衍生化辅助 MS 技术的现状和进展，并给出了它们的优势和挑战。总之，基于化学衍生化的脂质组学方法已成为分析复杂生物样品中脂质组学的一种有前途且可靠的技术。化学衍生策略与离子淌度质谱和环境质谱相结合显示出巨大的潜力。在此，我们总结了用于脂质组学分析的化学衍生化辅助 MS 技术的现状和进展，并给出了它们的优势和挑战。总之，基于化学衍生化的脂质组学方法已成为分析复杂生物样品中脂质组学的一种有前途且可靠的技术。化学衍生策略与离子淌度质谱和环境质谱相结合显示出巨大的潜力。在此，我们总结了用于脂质组学分析的化学衍生化辅助 MS 技术的现状和进展，并给出了它们的优势和挑战。总之，基于化学衍生化的脂质组学方法已成为分析复杂生物样品中脂质组学的一种有前途且可靠的技术。