New Advances in Separation Science for Metabolomics: Resolving Chemical Diversity in a Post-Genomic Era

Kuehnbaum, Naomi L.; Britz‐McKibbin, Philip

doi:10.1021/cr300484s

Cited by 314 publications

(225 citation statements)

References 525 publications

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“…NMR can be quantitative, but not very sensitive, which limits the number of metabolites that can be monitored. GC-MS, capillary electrophoresis (CE)-MS and LC-MS offer higher sensitivity than NMR, thereby increasing the number of detectable metabolites38. However, matrix and ion suppression effects can limit the number of quantifiable metabolites.…”

Section: Discussionmentioning

confidence: 99%

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Chen

Wang

et al. 2017

Sci Rep

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We report a chemical isotope labeling (CIL) liquid chromatography mass spectrometry (LC-MS) method generally applicable for tracking metabolomic changes from samples collected in an animal model for studying disease development and treatment. A rat model of surgically induced osteoarthritis (OA) was used as an example to illustrate the workflow and technical performance. Experimental duplicate analyses of 234 plasma samples were carried out using dansylation labeling LC-MS targeting the amine/phenol submetabolome. These samples composed of 39 groups (6 rats per group) were collected at multiple time points with sham operation, OA control group, and OA rats with treatment, separately, using glucosamine/Celecoxib and three traditional Chinese medicines (Epimedii folium, Chuanxiong Rhizoma and Bushen-Huoxue). In total, 3893 metabolites could be detected and 2923 of them were consistently detected in more than 50% of the runs. This high-coverage submetabolome dataset could be used to track OA progression and treatment. Many differentiating metabolites were found and 11 metabolites including 2-aminoadipic acid, saccharopine and GABA were selected as potential biomarkers of OA progression and OA treatment. This study illustrates that CIL LC-MS is a very useful technique for monitoring incremental metabolomic changes with high coverage and accuracy for studying disease progression and treatment in animal models.

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Section: Discussionmentioning

confidence: 99%

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Chen

Wang

et al. 2017

Sci Rep

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“…Soga and co-workers were the first to show the utility of CE-MS for the global profiling of metabolites in biological samples 9,10 . Until now, the feasibility and usefulness of CE-MS for metabolomics has been widely demonstrated [11][12][13][14][15] . CE is generally coupled to MS via a sheath-liquid interfacing technique 16,17 ; however, due to dilution of the capillary effluent by the sheath-liquid, the detection sensitivity is intrinsically compromised.…”

Section: Introductionmentioning

confidence: 99%

Sheathless Capillary Electrophoresis–Mass Spectrometry for Metabolic Profiling of Biological Samples

Zhang

Gulersonmez

Hankemeier

et al. 2016

JoVE

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In metabolomics, a wide range of analytical techniques is used for the global profiling of (endogenous) metabolites in complex samples. In this paper, a protocol is presented for the analysis of anionic and cationic metabolites in biological samples by capillary electrophoresis-mass spectrometry (CE-MS). CE is well-suited for the analysis of highly polar and charged metabolites as compounds are separated on the basis of their charge-to-size ratio. A recently developed sheathless interfacing design, i.e., a porous tip interface, is used for coupling CE to electrospray ionization (ESI) MS. This interfacing approach allows the effective use of the intrinsically low-flow property of CE in combination with MS, resulting in nanomolar detection limits for a broad range of polar metabolite classes. The protocol presented here is based on employing a bare fused-silica capillary with a porous tip emitter at low-pH separation conditions for the analysis of a broad array of metabolite classes in biological samples. It is demonstrated that the same sheathless CE-MS method can be used for the profiling of cationic metabolites, including amino acids, nucleosides and small peptides, or anionic metabolites, including sugar phosphates, nucleotides and organic acids, by only switching the MS detection and separation voltage polarity. Highly information-rich metabolic profiles in various biological samples, such as urine, cerebrospinal fluid and extracts of the glioblastoma cell line, can be obtained by this protocol in less than 1 hr of CE-MS analysis.

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“…Since non-volatile components with low polarity such as solanesols (12,13), chlorophyll derivatives (14), triacylglycerols (15), solanachromene (16) and phytosterols (17) (Figure 1) are also included in tobacco leaf and have been considered unsuitable for detection in using the previously employed instruments (8)(9)(10)(11), the metabolomics applied to tobacco leaves has yet to cover all the components in tobacco leaves. In the first place, comprehensive analyses for metabolomics consist of a separation and detection part which are hyphenated so as to maximize comprehensiveness of method (7,(18)(19)(20). Gas chromatography (GC) for volatile components (8,9,21), liquid chromatography (LC) for components with low to high polarity (11,22) and capillary electrophoresis (CE) for hydrophilic components (23) have therefore been selected in comprehensive analysis according to the chemical characters of target components.…”

Section: Introductionmentioning

confidence: 99%

A Simultaneous Analytical Method to Profile Non-Volatile Components with Low Polarity Elucidating Differences Between Tobacco Leaves Using Atmospheric Pressure Chemical Ionization Mass Spectrometry Detection

Ishida

2016

Beiträge Zur Tabakforschung International/Contributions to Tobacco Research

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SUMMARYA comprehensive analytical method using liquid chromatography atmospheric pressure chemical ionization mass spectrometry detector (LC/APCI-MSD) was developed to determine key non-volatile components with low polarity elucidating holistic difference among tobacco leaves. Nonaqueous reversed-phase chromatography (NARPC) using organic solvent ensured simultaneous separation of various components with low polarity in tobacco resin. Application of full-scan mode to APCI-MSD hyphenated with NARPC enabled simultaneous detection of numerous intense product ions given by APCI interface. Parameters for data processing to filter, feature and align peaks were adjusted in order to strike a balance between comprehensiveness and reproducibility in analysis. 63 types of components such as solanesols, chlorophylls, phytosterols, triacylglycerols, solanachromene and others were determined on total ion chromatograms according to authentic components, wavelength spectrum and mass spectrum. The whole area of identified entities among the ones detected on total ion chromatogram reached to over 60% and major entities among those identified showed favorable linearity of determination coefficient of over 0.99. The developed method and data processing procedure were therefore considered feasible for subsequent multivariate analysis. Data matrix consisting of a number of entities was then subjected to principal component analysis (PCA) and hierarchical clustering analysis. Cultivars of tobacco leaves were distributed far from each cultivar on PCA score plot and each cluster seemed to be characterized by identified non-volatile components with low polarity. While fluecured Virginia (FCV) was loaded by solanachromene, phytosterol esters and triacylglycerols, free phytosterols and chlorophylls loaded Burley (BLY) and Oriental (ORI) respectively. Consequently the whole methodology consisting of comprehensive method and data processing procedure proved useful to determine key-components among cultivars of tobacco leaves, and was expected to additionally expand coverage that metabolomics study has ensured. [Beitr. Tabakforsch. Int. 27 (2016)

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New Advances in Separation Science for Metabolomics: Resolving Chemical Diversity in a Post-Genomic Era

Cited by 314 publications

References 525 publications

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Sheathless Capillary Electrophoresis–Mass Spectrometry for Metabolic Profiling of Biological Samples

A Simultaneous Analytical Method to Profile Non-Volatile Components with Low Polarity Elucidating Differences Between Tobacco Leaves Using Atmospheric Pressure Chemical Ionization Mass Spectrometry Detection

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New Advances in Separation Science for Metabolomics: Resolving Chemical Diversity in a Post-Genomic Era

Cited by 314 publications

References 525 publications

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Chemical Isotope Labeling LC-MS for Monitoring Disease Progression and Treatment in Animal Models: Plasma Metabolomics Study of Osteoarthritis Rat Model

Sheathless Capillary Electrophoresis&#8211;Mass Spectrometry for Metabolic Profiling of Biological Samples

A Simultaneous Analytical Method to Profile Non-Volatile Components with Low Polarity Elucidating Differences Between Tobacco Leaves Using Atmospheric Pressure Chemical Ionization Mass Spectrometry Detection

Contact Info

Product

Resources

About

Sheathless Capillary Electrophoresis–Mass Spectrometry for Metabolic Profiling of Biological Samples