High resolution ion mobility-mass spectrometry for separation and identification of isomeric lipids

Groessl, Michael; Gräf, Stephan; Knochenmuss, Richard

doi:10.1039/c5an00838g

Cited by 191 publications

(209 citation statements)

References 35 publications

(66 reference statements)

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“…2000 (Table 1), which is approximately an order of magnitude higher than current state-of-the-art instrumentation. 48–50 It should be noted, however, that this determination of separation potential for closely related isomers in Table 1 ( i.e. , within 0.4%) is based solely on the observable percent difference in CCS, which, for these small differences is approaching the certainly limit of the measurement (± 0.2–0.3%).…”

Section: Resultsmentioning

confidence: 90%

Investigation of the Complete Suite of the Leucine and Isoleucine Isomers: Toward Prediction of Ion Mobility Separation Capabilities

2016

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In this study we investigated 11 isomers with the molecular formula C6H13NO2 (m/z 131) to ascertain the potential of utilizing drift tube ion mobility mass spectrometry to aid in the separation of isomeric mixtures. This study of small molecules provides a detailed examination of the application of uniform field ion mobility for a narrow scope of isomers with variations in both bond coordination and stereochemistry. For small molecules, it was observed that in general constitutional isomers are more readily separated by uniform field mobility in comparison to stereoisomers such as enantiomers or diastereomers. Diastereomers exhibited differences in their collision cross section (CCS), but were unresolvable in a mixture, whereas the enantiomers studied did not exhibit statistically different CCS values. A mathematical relationship relating the CCS to resolving power was developed in order to predict the required ion mobility resolving power needed to separate the various isomer classes. For the majority of isomers evaluated in this study, a uniform field-based resolving power of 100 was predicted to be sufficient to resolve over half (ca. 60%) of all hypothetical isomer pairs, including leucine and isoleucine, whereas their stereoisomers (D- and L-forms) are predicted to be significantly more challenging, if not impossible, to separate by conventional drift tube techniques.

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Section: Resultsmentioning

confidence: 90%

Investigation of the Complete Suite of the Leucine and Isoleucine Isomers: Toward Prediction of Ion Mobility Separation Capabilities

2016

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“…Separating these compounds based purely on mobility alone would require 280 resolving power or less, which is currently obtainable (Table S2). 30,57,61 To separate ca. 95% (CCS ≥ 0.02%) of the peptides by IM alone would require about 7,000 mobility resolving power.…”

Section: Resultsmentioning

confidence: 99%

Correlating Resolving Power, Resolution, and Collision Cross Section: Unifying Cross-Platform Assessment of Separation Efficiency in Ion Mobility Spectrometry

2017

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Here we examine the relationship between resolving power (Rp), resolution (Rpp), and collision cross section (CCS) for compounds analyzed in previous ion mobility (IM) experiments representing a wide variety of instrument platforms and IM techniques. Our previous work indicated these three variables effectively describe and predict separation efficiency for drift tube ion mobility spectrometry (DTIMS) experiments. In this work we seek to determine if our previous findings are a general reflection of IM behavior applicable to various instrument platforms and mobility techniques. Results suggest IM distributions are well characterized by a Gaussian model and separation efficiency can be predicted based on empirical difference in the gas-phase CCS and a CCS-based resolving power definition (CCS/ΔCCS). Notably traveling wave (TWIMS) was found to operate at substantially higher resolutions than a single-peak resolving power suggested. When a CCS-based Rp definition was utilized, TWIMS was found to operate at a resolving power of between 40 and 50, confirming the previous observations by Giles and coworkers. After converting the separation axis (and corresponding resolving power) to cross section space it is possible to effectively predict separation behavior for all mobility techniques evaluated (i.e. uniform field, trapped ion mobility, traveling wave, cyclic and overtone instruments) using the equations described in this work. Finally, we are able to establish for the first time that the current state-of-the-art ion mobility separations benchmark at a CCS-based resolving powers above 300 which is sufficient to differentiate analyte ions with CCS differences as small as 0.5%.

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“…Previous work by Baker and coworkers (49) reported that positional isomers of phospholipids could be differentiated by IM separation, but the difference between the drift times of each pair of isomers is less than 1%, which is beyond the resolution of our instrument. In another study by Groessl et al (52), the effect of E/Z isomers on the CCS of PC(18:1/18:1) was also found to be less than 0.5%.…”

Section: Ccs Measurements Of Lipids By Twim-ms Calibrationmentioning

confidence: 99%

Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics

Hines

Herron

2017

Journal of Lipid Research

117

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implicated in a number of human diseases, such as atherosclerosis (3), nonalcoholic fatty liver (4), diabetes (5), Alzheimer's disease (6), and cancer (7,8). Advances in lipidomic techniques and strategies, led by the LIPID MAPS consortium, have greatly enhanced our understanding of the distribution and biological roles of lipids (9-13). Modern mass spectrometry (MS), coupled with electrospray ionization (ESI), is the key to qualitative and quantitative lipidomic analysis. Typical MS-based lipidomic strategies are shotgun (i.e., direct infusion) lipidomics (9, 14) and liquid chromatography (LC)-MS lipidomics (11,15,16). Shotgun lipidomics relies on partial intrasource separation of lipid classes through varying the pH of the lipid solution and identification of lipid species by their characteristic fragmentation in tandem MS analysis (9,17). This approach has the advantage of being high-throughput, but it also has several disadvantages: a) suppression of low-abundant species by major polar lipids such as phosphatidylcholines; b) difficulty in analysis of lipid species that are poorly ionized by ESI; and c) inability to provide structural information on isobaric and isomeric species. The LC-MS-based strategy utilizes targeted analysis of each lipid class under conditions that are optimized for that particular class (11,15,16,18). This strategy has the advantages of being specific, sensitive, and comprehensive, but it also has limitations, such as being time consuming and less cost effective. To increase the throughput of the LC-MS lipidomics while maintaining the specificity and sensitivity, we desire improved chromatographic techniques and additional dimensions of separation that are orthogonal to LC and MS. Lipids play important roles in maintaining membrane structures and mediating signaling pathways (1, 2). Dysregulated lipid biosynthesis and metabolism have been Abstract Ion mobility-mass spectrometry (IM-MS) has proven to be a highly informative technique for the characterization of lipids from cells and tissues. We report the combination of hydrophilic-interaction liquid chromatography (HILIC) with traveling-wave IM-MS (TWIM-MS

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High resolution ion mobility-mass spectrometry for separation and identification of isomeric lipids

Cited by 191 publications

References 35 publications

Investigation of the Complete Suite of the Leucine and Isoleucine Isomers: Toward Prediction of Ion Mobility Separation Capabilities

Investigation of the Complete Suite of the Leucine and Isoleucine Isomers: Toward Prediction of Ion Mobility Separation Capabilities

Correlating Resolving Power, Resolution, and Collision Cross Section: Unifying Cross-Platform Assessment of Separation Efficiency in Ion Mobility Spectrometry

Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics

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