Performance enhancement in the measurement of 5 endogenous steroids by LC–MS/MS combined with differential ion mobility spectrometry

Ray, Julie A.; Kushnir, Mark M.; Yost, Richard A.; Rockwood, Alan L.; Meikle, A.W.

doi:10.1016/j.cca.2014.07.036

Cited by 76 publications

(67 citation statements)

References 35 publications

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“…in untargeted discovery experiments such as data-dependent and data-independent acquisitions ( 27,28 ).…”

Section: Hilic-uplc Msmentioning

confidence: 99%

“…Considering the huge diversity of lipid molecular species present in a biological sample, neither strategy alone is suffi cient to resolve isobaric interference during MS analysis. To test the concept of DMS as an orthogonal separation noise levels from endogenous interferences ( 27,28 ); MRMs are traditionally blind to the presence of such closely related species. In biological samples such as serum, there is increased background noise that contributes to a loss in sensitivity and selectivity for HILIC LC/MS.…”

Section: Rp-uplc and Enhancement With Dmsmentioning

confidence: 99%

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Three-dimensional enhanced lipidomics analysis combining UPLC, differential ion mobility spectrometry, and mass spectrometric separation strategies

Baker

Armando

Campbell

et al. 2014

Journal of Lipid Research

116

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This article is available online at http://www.jlr.org technique generates charged molecules (i.e., for m/z < 1,000 Da) without signifi cant analyte decomposition ( 4 ). The technique also enables the coupling of HPLC to MS, effectively converting liquid-phase molecules into gasphase ions. Another leap in technology was the introduction of the triple quadrupole mass spectrometer ( 5 ), which when combined with ESI, enables facile, sensitive, and specifi c analyses of complex lipid mixtures ( 6, 7 ). Using ESI-MS, semitargeted scan modes, which exploit unique ion fragmentation patterns during MS/MS experiments, were developed that are presently used to isolate categories and classes of lipids without the need for complex LC separation, a technique termed "shotgun" lipidomics ( 8 ). There are several technical limitations of this approach including restricted detection of minor lipid components due to instrumental constraints of the dynamic range and discrimination against low-abundant and/or poorly ionizable lipids. Furthermore, ion suppression and diffi culty in differentiating lipids with overlapping fragmentation patterns underline the importance of chromatographic separation prior to MS analysis. A practical alternative to a global lipidomics methodology is a targeted lipidomics approach that utilizes extraction and analysis protocols that are optimized for each lipid category and class ( 9 ), providing an effective tool to identify Abstract Phospholipids serve as central structural components in cellular membranes and as potent mediators in numerous signaling pathways. There are six main classes of naturally occurring phospholipids distinguished by their distinct polar head groups that contain many unique molecular species with distinct fatty acid composition. Phospholipid molecular species are often expressed as isobaric species that are denoted by the phospholipid class and the total number of carbon atoms and double bonds contained in the esterifi ed fatty acyl groups (e.g., phosphatidylcholine 34:2). Techniques to separate these molecules exist, and each has positive and negative attributes. Hydrophilic interaction liquid chromatography uses polar bonded silica to separate lipids by polar head group but not by specifi c molecular species. Reversed phase (RP) chromatography can separate by fatty acyl chain composition but not by polar head group. Herein we describe a new strategy called differential ion mobility spectrometry (DMS), which separates phospholipid classes by their polar head group. Combining DMS with current LC methods enhances phospholipid separation by increasing resolution, specifi city, and signal-to-noise ratio. Additional application of specialized information-dependent acquisition methodologies along with RP chromatography allows full isobaric resolution, identifi cation, and compositional characterization of specifi c phospholipids at the molecular level. The modern fi eld of lipidomics began with the advent of ESI-MS [for review, see ( 1-3 )]. This "soft" ionization

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“…in untargeted discovery experiments such as data-dependent and data-independent acquisitions ( 27,28 ).…”

Section: Hilic-uplc Msmentioning

confidence: 99%

Section: Rp-uplc and Enhancement With Dmsmentioning

confidence: 99%

Three-dimensional enhanced lipidomics analysis combining UPLC, differential ion mobility spectrometry, and mass spectrometric separation strategies

Baker

Armando

Campbell

et al. 2014

Journal of Lipid Research

116

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“…They play a much larger role beyond proof-of-concept studies where population diversity greatly increases. Having a toolkit of approaches to recognize (accurate mass, MS 3 ) and resolve (LC, differential mobility, MRM) them is critical to keeping studies on track [39,40].…”

Section: Knowing Your Samples and Subjectsmentioning

confidence: 99%

Making Methods Rugged for Regulated Bioanalysis

et al. 2015

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Methods started in discovery are optimized as they progress through preclinical and clinical development. Making a robust assay includes testing individual steps for consistency and points of failure. Assays may be transferred, optimized and revalidated several times. A rugged assay will not only meet regulatory requirements, but will execute with a low failure rate and confirm results under repeat analysis. Challenging aspects such as differential recovery, sample stabilization, resolution of isomers or conjugate analysis must be tackled and made routine. The proper selection of the IS can overcome limitations. It is best to know the potential points of failure before a study has started, but lessons learned from each study also provide invaluable insights to improve assay ruggedness.

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“…Beyond commonly analyzed compounds such as carbohydrates and lipids, several other clinically relevant compound classes have been analyzed with IMS. For example, separation has been achieved for isomers within the diverse class of steroids, with rapid analysis by LC-FAIMS-MS (70 ) and by strategies such as derivatization (71 ) and sodiated dimerization (72 ). Furthermore, epimers of vitamin D metabolites have been also separated on the basis of differences in the mobility of their sodiated dimers (73 ).…”

Section: Ion Mobility In Clinical Analysismentioning

confidence: 99%

Ion Mobility in Clinical Analysis: Current Progress and Future Perspectives

et al. 2016

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BACKGROUND Ion mobility spectrometry (IMS) is a rapid separation tool that can be coupled with several sampling/ionization methods, other separation techniques (e.g., chromatography), and various detectors (e.g., mass spectrometry). This technique has become increasingly used in the last 2 decades for applications ranging from illicit drug and chemical warfare agent detection to structural characterization of biological macromolecules such as proteins. Because of its rapid speed of analysis, IMS has recently been investigated for its potential use in clinical laboratories. CONTENT This review article first provides a brief introduction to ion mobility operating principles and instrumentation. Several current applications will then be detailed, including investigation of rapid ambient sampling from exhaled breath and other volatile compounds and mass spectrometric imaging for localization of target compounds. Additionally, current ion mobility research in relevant fields (i.e., metabolomics) will be discussed as it pertains to potential future application in clinical settings. SUMMARY This review article provides the authors' perspective on the future of ion mobility implementation in the clinical setting, with a focus on ambient sampling methods that allow IMS to be used as a “bedside” standalone technique for rapid disease screening and methods for improving the analysis of complex biological samples such as blood plasma and urine.

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Performance enhancement in the measurement of 5 endogenous steroids by LC–MS/MS combined with differential ion mobility spectrometry

Cited by 76 publications

References 35 publications

Three-dimensional enhanced lipidomics analysis combining UPLC, differential ion mobility spectrometry, and mass spectrometric separation strategies

Three-dimensional enhanced lipidomics analysis combining UPLC, differential ion mobility spectrometry, and mass spectrometric separation strategies

Making Methods Rugged for Regulated Bioanalysis

Ion Mobility in Clinical Analysis: Current Progress and Future Perspectives

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