Correlations between the dimensions of a 2-D separation create trend lines that depend on structural or chemical characteristics
of the compound class and thus facilitate classification of unknowns. This broadly applies to conventional ion mobility spectrometry
(IMS)/mass spectrometry (MS), where the major biomolecular classes (e.g., lipids, peptides, nucleotides) occupy different
trend line domains. However, strong correlation between the IMS and MS separations for ions of same charge has impeded finer
distinctions. Differential IMS (or FAIMS) is generally less correlated to MS and thus could separate those domains better.
We report the first observation of chemical class separation by trend lines using FAIMS, here for lipids. For lipids, FAIMS
is indeed more independent of MS than conventional IMS, and subclasses (such as phospho-, glycero-, or sphingolipids) form
distinct, often non-overlapping domains. Even finer categories with different functional groups or degrees of unsaturation
are often separated. As expected, resolution improves in He-rich gases: at 70% He, glycerolipid isomers with different fatty
acid positions can be resolved. These results open the door for application of FAIMS to lipids, particularly in shotgun lipidomics
and targeted analyses of bioactive lipids. 相似文献
Paclitaxel (PTX) is a popular anticancer drug used in the treatment of various types of cancers. PTX is metabolized in the human liver by cytochrome P450 to two structural isomers, 3′-p-hydroxypaclitaxel (3p-OHP) and 6α-hydroxypaclitaxel (6α-OHP). Analyzing PTX and its two metabolites, 3p-OHP and 6α-OHP, is crucial for understanding general pharmacokinetics, drug activity, and drug resistance. In this study, electrospray ionization ion mobility mass spectrometry (ESI-IM-MS) and collision induced dissociation (CID) are utilized for the identification and characterization of PTX and its metabolites. Ion mobility distributions of 3p-OHP and 6α-OHP indicate that hydroxylation of PTX at different sites yields distinct gas phase structures. Addition of monovalent alkali metal and silver metal cations enhances the distinct dissociation patterns of these structural isomers. The differences observed in the CID patterns of metalated PTX and its two metabolites are investigated further by evaluating their gas-phase structures. Density functional theory calculations suggest that the observed structural changes and dissociation pathways are the result of the interactions between the metal cation and the hydroxyl substituents in PTX metabolites.
The chemical components analysis of single cell is important for the understanding of physiological processes such as cell growth, signal transduction and apoptosis. Time-of-flight secondary ion mass spectrometry (ToF-SIMS) is a sensitive surface analysis technique with high spatial resolution, which has been used for single cell and micro-area analysis. However, relatively low ionization yield of biomolecules limited its wide applications in single cell analysis. Herein, we used metal substrate and matrix material to enhance the ionization yield of lipids. The signal intensity of phosphatidylcholine (PC 40:0) casted on the matrix/gold-coated silicon substrate was 65 times higher than that on the silicon wafer. The signal enhancement of phosphatidylcholine (PC 34:1) on single cell surface cultured on matrix/gold-coated silicon substrate was observed as well. Owing to the influence of irregular topography and complex chemical environment of cell, the increase of lipids signal was smaller. Delayed extraction mode of ToF-SIMS overcame the effects of cell topography, leading to further enhancement of the signal intensity of lipids. Meanwhile, simultaneous high spatial resolution of chemical imaging and high mass resolution of the mass spectra of single cells were obtained. Our strategies provided new insights into the study of cell metabolism and cell-environment interactions. 相似文献
Ion mobility measurements of product ions were used to characterize the collisional cross section (CCS) of various complex lipid [M-H]? ions using traveling wave ion mobility mass spectrometry (TWIMS). TWIMS analysis of various product ions derived after collisional activation of mono- and dihydroxy arachidonate metabolites was found to be more complex than the analysis of intact molecular ions and provided some insight into molecular mechanisms involved in product ion formation. The CCS observed for the molecular ion [M-H]? and certain product ions were consistent with a folded ion structure, the latter predicted by the proposed mechanisms of product ion formation. Unexpectedly, product ions from [M-H-H2O-CO2]? and [M-H-H2O]? displayed complex ion mobility profiles suggesting multiple mechanisms of ion formation. The [M-H-H2O]? ion from LTB4 was studied in more detail using both nitrogen and helium as the drift gas in the ion mobility cell. One population of [M-H-H2O]? product ions from LTB4 was consistent with formation of covalent ring structures, while the ions displaying a higher CCS were consistent with a more open-chain structure. Using molecular dynamics and theoretical CCS calculations, energy minimized structures of those product ions with the open-chain structures were found to have a higher CCS than a folded molecular ion structure. The measurement of product ion mobility can be an additional and unique signature of eicosanoids measured by LC-MS/MS techniques.
