Divergent Metabolic Fates of Aromatic Amino Acid-Derived Isomers: Insights from Ex Vivo Metabolomics and HDX-HRMS/MS-Based Resolution of Tautomers.

Tautomers are one of the many types of isomers, and differences in tautomeric structures confer altered chemical and biological properties. Using ultrahigh-performance liquid chromatography-high-resolution mass spectrometry (UHPLC-HRMS) ex vivo metabolomics, we investigate, in whole blood, the divergent metabolism of enol and keto forms of indole-3-pyruvate (IPyA), a tautomeric product of aromatic amino acid metabolism. Two new compounds resulting from IPyA metabolism were discovered, 3-(1-indol-3-yl)-2,3-dioxopropanoic acid or "indole-3-oxopyruvic acid" and glutathionyl-indole pyruvate (GSHIPyA), which were characterized via ultraviolet photodissociation (UVPD) and higher-energy collisional dissociation (HCD).

Multimodal Image Fusion Workflow Incorporating MALDI Imaging Mass Spectrometry and Microscopy for the Study of Small Pharmaceutical Compounds.

Multimodal imaging analyses of dosed tissue samples can provide more comprehensive insights into the effects of a therapeutically active compound on a target tissue compared to single-modal imaging. For example, simultaneous spatial mapping of pharmaceutical compounds and endogenous macromolecule receptors is difficult to achieve in a single imaging experiment. Herein, we present a multimodal workflow combining imaging mass spectrometry with immunohistochemistry (IHC) fluorescence imaging and brightfield microscopy imaging.

Enhancing Spatial Resolution in Tandem Mass Spectrometry Ion/Ion Reaction Imaging Experiments through Image Fusion.

We have recently developed a charge inversion ion/ion reaction to selectively derivatize phosphatidylserine lipids via gas-phase Schiff base formation. This tandem mass spectrometry (MS/MS) workflow enables the separation and detection of isobaric lipids in imaging mass spectrometry, but the images acquired using this workflow are limited to relatively poor spatial resolutions due to the current time and limit of detection requirements for these ion/ion reaction imaging mass spectrometry experiments. This trade-off between chemical specificity and spatial resolution can be overcome by using computational image fusion, which combines complementary information from multiple images.