Life Sciences Mass Spectrometry, Department of Inorganic and Analytical Chemistry, University of Geneva, 24 Quai Ernest Ansermet, 1211, Geneva 4, Switzerland.
Anal Bioanal Chem. 2023 Apr;415(10):1905-1915. doi: 10.1007/s00216-023-04602-0. Epub 2023 Feb 23.
The benefits of combining drift time ion mobility (DTIMS) with liquid chromatography-high-resolution mass spectrometry (HRMS) have been reported for metabolomics but the use of differential time mobility spectrometry (DMS) is less obvious due to the need for rapid scanning of the DMS cell. Drift DTIMS provides additional precursor ion selectivity and collisional cross-section information but the separation resolution between analytes remains cell- and component-dependent. With DMS, the addition of 2-propanol modifier can improve the selectivity but on cost of analyte MS response. In the present work, we investigate the liquid chromatography-mass spectrometry (LC-MS) analysis of a mix of 50 analytes, representative for urine and plasma metabolites, using scanning DMS with the single modifiers cyclohexane (Ch), toluene (Tol), acetonitrile (ACN), ethanol (EtOH), and 2-propanol (IPA), and a binary modifier mixture (cyclohexane/2-propanol) with emphasis on selectivity and signal sensitivity. 1.5% IPA in the N stream was found to suppress the signal of 50% of the analytes which could be partially recovered with the use of IPA to 0.05% as a Ch/IPA mixture. The potential to use the separation voltage/compensation voltage/modifier (SV/CoV/Mod) feature as an additional analyte identifier for qualitative analysis is also presented and applied to a data-independent LCxDMS-SWATH-MS workflow for the analysis of endogenous metabolites and drugs of abuse in human urine samples from traffic control.
组合漂移时间离子淌度（DTIMS）与液相色谱-高分辨质谱（HRMS）在代谢组学中已经显示出了益处，但由于需要快速扫描 DMS 池，差分时间迁移谱（DMS）的使用不太明显。漂移 DTIMS 提供了额外的前体离子选择性和碰撞截面信息，但分析物之间的分离分辨率仍然取决于池和组件。使用 DMS 时，添加 2-丙醇修饰剂可以提高选择性，但代价是分析物的 MS 响应。在本工作中，我们研究了使用扫描 DMS 对 50 种分析物的混合物（代表尿液和血浆代谢物）进行液相色谱-质谱（LC-MS）分析，使用的单修饰剂为环己烷（Ch）、甲苯（Tol）、乙腈（ACN）、乙醇（EtOH）和 2-丙醇（IPA），以及双修饰剂混合物（环己烷/2-丙醇），重点关注选择性和信号灵敏度。在 N 流中发现 1.5%IPA 抑制了 50%分析物的信号，通过使用 IPA 至 0.05%作为 Ch/IPA 混合物可以部分恢复。还提出了将分离电压/补偿电压/修饰剂（SV/CoV/Mod）功能用作定性分析的另一个分析物标识符的潜力，并应用于一种数据独立的 LCxDMS-SWATH-MS 工作流程，用于分析来自交通管制的人类尿液样品中的内源性代谢物和滥用药物。
