Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods
Analyzing complex mixtures of drug-like molecules: Ion mobility as an adjunct to existing liquid chromatography-(tandem) mass spectrometry methods
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DOI：
10.1016/j.chroma.2017.02.015
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发表时间：
2017-03-25
影响因子：
4.1
通讯作者：
Sobott, Frank
中科院分区：
文献类型：
--
作者：
Boschmans, Jasper;Lemiére, Filip;Sobott, Frank
行波离子迁移质谱（TWIMS）的使用进行了评估，结合，并作为一个可能的替代，传统的LC-MS（/MS）方法的药物样化合物和代谢物的分离和表征。作为一个模型系统，我们使用的化疗剂美法仑，这导致在十多个密切相关的水解产物和链状oligomerize.Ion迁移率作为过滤工具的结果在分离的干扰离子的离子感兴趣的离子的体外孵育混合物的电荷状态和形状/大小的基础上。不同类别的化合物通常显示不同的迁移率，即使它们显示相同的LC行为-从而提供正交分离维度。具有相同或相似m/z的小分子，仅在形状/大小上不同（例如异构体和同量异位素、单体/二聚体），也可以使用离子迁移率进行区分。类似的保留时间和质荷比，漂移时间是分析依赖性的，可以作为一个额外的identifier.We发现，化合物美法仑显示两个不同的漂移时间，由于形成气相电荷异构体（原异构体）。原异构体的发生具有重要意义的离子迁移率特性的分析物，也为他们的碎裂行为（CID）在气相中的解释。(C)2017爱思唯尔B. V.保留所有权利。
The use of traveling wave ion mobility mass spectrometry (TWIMS) is evaluated in conjunction with, and as a possible alternative to, conventional LC-MS(/MS) methods for the separation and characterization of drug-like compounds and metabolites. As a model system we use an in vitro incubation mixture of the chemotherapeutic agent melphalan, which results in more than ten closely related hydrolysis products and chain-like oligomers.Ion mobility as a filtering tool results in the separation of ions of interest from interfering ions, based on charge state and shape/size. Different classes of chemical compounds often display different mobilities even if they show the same LC behavior - thereby providing an orthogonal separation dimension. Small molecules with identical or similar m/z that only differ in shape/size (e.g. isomers and isobars, monomers/dimers) can also be distinguished using ion mobility. Similar to retention times and mass-to charge ratios, drift times are analyte-dependent and can be used as an additional identifier.We find that the compound melphalan shows two different drift times due to the formation of gas phase charge isomers (protomers). The occurrence of protomers has important implications for ion mobility characterization of such analytes, and also for the interpretation of their fragmentation behavior (CID) in the gas phase. (C) 2017 Elsevier B.V. All rights reserved.