Heightened awareness regarding the implication of disturbances in lipid metabolism with respect to prevalent human-related pathologies demands analytical techniques that provide unambiguous structural characterization and accurate quantitation of lipids in complex biological samples. The diversity in molecular structures of lipids along with their wide range of concentrations in biological matrices present formidable analytical challenges. Modern mass spectrometry (MS) offers an unprecedented level of analytical power in lipid analysis, as many advancements in the field of lipidomics have been facilitated through novel applications of and developments in electrospray ionization tandem mass spectrometry (ESI-MS/MS). ESI allows for the formation of intact lipid ions with little to no fragmentation and has become widely used in contemporary lipidomics experiments due to its sensitivity, reproducibility, and compatibility with condensed-phase modes of separation, such as liquid chromatography (LC). Owing to variations in lipid functional groups, ESI enables partial chemical separation of the lipidome, yet the preferred ion-type is not always formed, impacting lipid detection, characterization, and quantitation. Moreover, conventional ESI-MS/MS approaches often fail to expose diverse subtle structural features like the sites of unsaturation in fatty acyl constituents or acyl chain regiochemistry along the glycerol backbone, representing a significant challenge for ESI-MS/MS. To overcome these shortcomings, various charge manipulation strategies, including charge-switching, have been developed to transform ion-type and charge state, with aims of increasing sensitivity and selectivity of ESI-MS/MS approaches. Importantly, charge manipulation approaches afford enhanced ionization efficiency, improved mixture analysis performance, and access to informative fragmentation channels. Herein, we present a critical review of the current suite of solution-based and gas-phase strategies for the manipulation of lipid ion charge and type relevant to ESI-MS/MS.

人们越来越认识到脂质代谢紊乱对人类普遍相关病理的影响，需要分析技术来提供复杂生物样品中脂质的明确结构表征和准确定量。脂质分子结构的多样性及其在生物基质中的广泛浓度提出了巨大的分析挑战。现代质谱 (MS) 为脂质分析提供了前所未有的分析能力，电喷雾电离串联质谱 (ESI-MS/MS) 的新颖应用和发展促进了脂质组学领域的许多进步。 ESI 可以形成几乎没有碎片的完整脂质离子，并且由于其灵敏度、重现性以及与液相色谱 (LC) 等凝聚相分离模式的兼容性，已广泛应用于当代脂质组学实验。由于脂质官能团的变化，ESI 能够对脂质组进行部分化学分离，但并不总是形成优选的离子类型，从而影响脂质检测、表征和定量。此外，传统的 ESI-MS/MS 方法通常无法揭示各种微妙的结构特征，例如脂肪酰基成分的不饱和位点或甘油主链上的酰基链区域化学，这对 ESI-MS/MS 来说是一个重大挑战。为了克服这些缺点，人们开发了各种电荷操纵策略（包括电荷转换）来转换离子类型和电荷状态，目的是提高 ESI-MS/MS 方法的灵敏度和选择性。 重要的是，电荷操纵方法可以提高电离效率，改善混合物分析性能，并获得信息丰富的碎片通道。在此，我们对当前用于操纵与 ESI-MS/MS 相关的脂质离子电荷和类型的基于溶液和气相的策略套件进行了批判性回顾。