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An Untargeted Lipidomics Workflow Incorporating High-Resolution Demultiplexing (HRdm) Drift Tube Ion Mobility-Mass Spectrometry.
Koomen, David C; May, Jody C; Mansueto, Alexander J; Graham, Todd R; McLean, John A.
Afiliación
  • Koomen DC; Center for Innovative Technology, Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • May JC; Center for Innovative Technology, Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • Mansueto AJ; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • Graham TR; Department of Biological Sciences, Vanderbilt University, Nashville, Tennessee 37235, United States.
  • McLean JA; Center for Innovative Technology, Department of Chemistry, Vanderbilt University, Nashville, Tennessee 37235, United States.
J Am Soc Mass Spectrom ; 2024 Sep 14.
Article en En | MEDLINE | ID: mdl-39276100
ABSTRACT
Global discovery lipidomics can provide comprehensive chemical information toward understanding the intricacies of metabolic lipid disorders such as dyslipidemia; however, the isomeric complexity of lipid species remains an analytical challenge. Orthogonal separation strategies, such as ion mobility (IM), can be inserted into liquid chromatography-mass spectrometry (LC-MS) untargeted lipidomic workflows for additional isomer separation and high-confidence annotation, and the emergence of high-resolution ion mobility (HRIM) strategies provides marked improvements to the resolving power (Rp > 200) that can differentiate small structural differences characteristic of isomers. One such HRIM strategy, high-resolution demultiplexing (HRdm), utilizes multiplexed drift tube ion mobility spectrometry (DTIMS) with post-acquisition algorithmic deconvolution to access high IM resolutions while retaining the measurement precision inherent to the drift tube technique; however, HRdm has yet to be utilized in untargeted studies. In this manuscript, a proof-of-concept study using ATP10D dysfunctional murine models was investigated to demonstrate the utility of HRdm-incorporated untargeted lipidomic analysis pipelines. Total lipid features were found to increase by 2.5-fold with HRdm compared to demultiplexed DTIMS as a consequence of more isomeric lipids being resolved. An example lipid, PC 365, was found to be significantly higher in dysfunctional ATP10D mice with two resolved peaks observed by HRdm that were absent in both the functional ATP10D mice and the standard demultiplexed DTIMS acquisition mode. The benefits of utilizing HRdm for discerning isomeric lipids in untargeted workflows have the potential to enhance our analytical understanding of lipids related to disease complexity and biologically relevant studies.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Am Soc Mass Spectrom Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
Buscar en Google

Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Idioma: En Revista: J Am Soc Mass Spectrom Año: 2024 Tipo del documento: Article País de afiliación: Estados Unidos Pais de publicación: Estados Unidos