MSACL 2017 US Abstract

Ion Mobility/Mass Spectrometry for Metabolomics and Clinical Analysis

Richard Yost (Presenter)
University of Florida

Bio: Rick Yost is the Colonel Allen R. and Margaret G. Crow Professor and Head of Analytical Chemistry at the University of Florida. He is also Director of the NIH Southeast Center for Integrated Metabolomics as well as a Professor both of Pathology, Immunology, and Laboratory Medicine and of Natural Resources and the Environment at UF. He also serves as Adjunct Professor of Pathology at the University of Utah/ARUP. Dr. Yost research interests are in the field of analytical mass spectrometry and its application to clinical and metabolomic analysis. He is currently the Vice President of the ASMS. He is probably best known for the invention of the triple quadrupole tandem mass spectrometer.

Authorship: Richard A Yost*, Christopher D. Chouinard, Nicholas R. Oranzi, Allison J. Levy, Robin Kemperman, Michael Wei
University of Florida

Short Abstract

Ion mobility/mass spectrometry has tremendous potential for metabolomics and clinical analysis. Ion mobility can resolve compounds unresolved by LC/MS/MS, provide additional structural information not available from mass spectrometry, and reduce or even eliminate the need for chromatographic separation. These features offer significant improvements for quantitative targeted metabolomics and clinical analysis, as well as for untargeted (global) metabolomics studies. Techniques to be covered include both classic drift tube ion mobility (IMS) and high-field asymmetric-waveform ion mobility (FAIMS), with various applications including steroids, bile acids, and Vitamin D.

Long Abstract

Ion mobility spectrometry (IMS) is a technique used to study gas-phase ions as they travel through an electric field. An advantage of ion mobility, in contrast to mass spectrometry, is that ions can be separated based on differences in their shape; this allows the potential for rapid separation of isomers that may otherwise be difficult or impossible to resolve with conventional methods such as LC/MS/MS. However, limitations in the resolving power of current commercial IMS instrumentation often require utilization of novel strategies to affect separation, especially for stereoisomers.

Our group has focused on metabolomics and clinical studies, with an emphasis on steroids and other related compounds such as Vitamin D metabolites. We have worked on several strategies for improving separation of these compounds, including addition of metal cations, complexation, and drift gas modification. These studies have utilized drift tube IMS (DTIMS), with an Agilent 6560 IM-QTOF instrument, to separate groups of isomers including pregnenolone/5α-dihydroprogesterone (5αDHP), androsterone/trans-androsterone, testosterone/dehydroepiandrosterone/epitestosterone, and the 25-hydroxyvitamin D2 and D3 epimers. Although many of these pairs may be separated by collision cross section as protonated species [M+H]+, such as the structural isomers pregnenolone (176.7 Å2) and 5αDHP (191.4 Å2), other groups require use of the aforementioned strategies. As an example, epimers androsterone and trans-androsterone are unresolved as protonated/sodiated monomers but are readily separated as sodiated dimers (242.6 Å2 and 256.3 Å2, respectively). Improvement in resolution with larger drift gases is also well demonstrated for dehydroepiandrosterone and epitestosterone, which are unresolved with helium, argon, and nitrogen, but better separated with carbon dioxide. Finally, cationization of 25-hydroxyvitamin D3 epimers reveals differences in the gas-phase conformations of the monomers, which can be improved by addition of larger alkali (e.g., K+, Rb+, Cs+) or alkaline earth metal ions (e.g., Mg+2, Ca+2).

As an alternative, FAIMS offers targeted separation with a considerably smaller instrumental footprint than DTIMS, making it a preferred platform for work in targeted, high throughput labs. Studies are underway with FAIMS to evaluate this approach for rapid differentiation of the aforementioned isomeric and epimeric steroids. An Owlstone chip-based FAIMS setup (Cambridge, UK) provides mobility measurements, coupled with a Thermo Scientific LTQ XL linear ion trap instrument for MS/MS acquisition. These studies are utilizing several strategies to augment separation, including formation of various cation adducts and modification of FAIMS cell environment (e.g., buffer gas and solvent additions). Examples will include introduction of alkali, alkaline earth, and transition metal cations such as lithium, magnesium, and manganese, respectively. Furthermore, the FAIMS cell buffer gas may be changed (e.g., carbon dioxide) and modified with solvent (e.g., methanol, isopropanol), as this strategy has previously been shown to improve FAIMS separation of small molecule isomers.


References & Acknowledgements:


Financial Disclosure

DescriptionY/NSource
GrantsyesAgilent, Wellspring, Prosolia, Breathtec, Cannabix
Salaryno
Board MemberyesASMS Board of Directors
Stockno
ExpensesyesAgilent, Breathtec

IP Royalty: no

Planning to mention or discuss specific products or technology of the company(ies) listed above:

yes