Enhancing the Power of Liquid Chromatography–Mass Spectrometry-Based Urine Metabolomics in Negative Ion Mode by Optimization of the Additive

Zhang, Xumin; Clausen, Morten Rahr; Zhao, Xiaolu; Zheng, Hong; Bertram, Hanne Christine

doi:10.1021/ac3013835

Cited by 42 publications

(50 citation statements)

References 21 publications

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“…Detection limits are especially pertinent for negative mode LC-MS workflows because of the lower flux of precursor ions generated compared to using the positive ESI mode [53–56]. Several LC mobile phase additives have been reported to improve ESI efficiency in the negative mode including acetic acid (pH 4) and ammonium hydroxide (pH 11) [57,58]; however, prolonged exposure to acidic solutions may result in hydrolysis of sulfate and thus should be avoided in favor of higher pH alternatives [59]. At the same time, high pH solutions were damaging to the LC system hardware and column and ultimately were abandoned in favor of more robust separations at neutral pH using 5 mM ammonium acetate-containing mobile phases.…”

Section: Resultsmentioning

confidence: 99%

“…At the same time, high pH solutions were damaging to the LC system hardware and column and ultimately were abandoned in favor of more robust separations at neutral pH using 5 mM ammonium acetate-containing mobile phases. Additionally methanol was used instead of acetonitrile as the organic mobile phase constituent to further boost the ESI efficiency [57]. …”

Section: Resultsmentioning

confidence: 99%

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Direct Identification of Tyrosine Sulfation by using Ultraviolet Photodissociation Mass Spectrometry

Robinson

Moore

Brodbelt

2014

J. Am. Soc. Mass Spectrom.

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Sulfation is a common post-translational modification of tyrosine residues in eukaryotes; however, detection using traditional liquid chromatography-mass spectrometry (LC-MS) methods is challenging based on poor ionization efficiency in the positive ion mode and facile neutral loss upon collisional activation. In the present study, 193 nm ultraviolet photodissociation (UVPD) is applied to sulfopeptide anions to generate diagnostic sequence ions which do not undergo appreciable neutral loss of sulfate even using higher energy photoirradiation parameters. At the same time, neutral loss of sulfate is observed from the precursor and charge reduced precursor ions, a spectral feature that is useful for differentiating tyrosine sulfation from the nominally isobaric tyrosine phosphorylation. LC-MS detection limits for UVPD analysis in the negative mode were determined to be around 100 fmol for three sulfated peptides, caerulein, cionin, and leu-enkephalin. The LC-UVPD-MS method was applied for analysis of bovine fibrinogen, and its key sulfated peptide was confidently identified.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Direct Identification of Tyrosine Sulfation by using Ultraviolet Photodissociation Mass Spectrometry

Robinson

Moore

Brodbelt

2014

J. Am. Soc. Mass Spectrom.

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show abstract

“…20 In brief, separation was performed on a ZORBAX SB C18 column (0.5 × 150 mm, 3.5 μm, Agilent Technologies, Waldbronn, Germany) at 25 °C using a gradient of water and acetonitrile containing 0.1% formic acid. All analyses were carried out in duplicate, and the MS was operated in negative mode.…”

Section: Methodsmentioning

confidence: 99%

“…20 For urine mass spectral data, compound features extracted with MZmine were subjected to multivariate data analysis using SIMCA-P+ (Umetrics AB, Umeå, Sweden). Peak areas were normalized to the total peak area and each variable was mean-centered and autoscaled.…”

Section: Methodsmentioning

confidence: 99%

Urinary Loss of Tricarboxylic Acid Cycle Intermediates As Revealed by Metabolomics Studies: An Underlying Mechanism to Reduce Lipid Accretion by Whey Protein Ingestion?

et al. 2014

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Whey protein intake is associated with the modulation of energy metabolism and altered body composition both in human subjects and in animals, but the underlying mechanisms are not yet elucidated. We fed obesity-prone C57BL/6J mice high-fat diets with either casein (HF casein) or whey (HF whey) for 6 weeks. At equal energy intake and apparent fat and nitrogen digestibility, mice fed HF whey stored less energy as lipids, evident both as lower white adipose tissue mass and as reduced liver lipids, compared with HF-casein-fed mice. Explorative analyses of 48 h urine, both by 1H NMR and LC–MS metabolomic platforms, demonstrated higher urinary excretion of tricarboxylic acid (TCA) cycle intermediates citric acid and succinic acid (identified by both platforms), and cis-aconitic acid and isocitric acid (identified by LC–MS platform) in the HF whey, relative to in the HF-casein-fed mice. Targeted LC–MS analyses revealed higher citric acid and cis-aconitic acid concentrations in fed state plasma, but not in liver of HF-whey-fed mice. We propose that enhanced urinary loss of TCA cycle metabolites drain available substrates for anabolic processes, such as lipogenesis, thereby leading to reduced lipid accretion in HF-whey-fed compared to HF-casein-fed mice.

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“…Different molecular species beyond simply [M + H] + and [M − H] − should be included for each compound to capture the whole width and breadth of possible adducts . That includes a variety of mobile phase modifiers and solvent related ions as well as sodium and ammonium adducts or commonly observed water loss . To allow for high spectral quality, a high enough number of spectra for each adducts type has to be obtained and later averaged.…”

Section: Creation Of Ms/ms Databasesmentioning

confidence: 99%

Identification of small molecules using accurate mass MS/MS search

Kind

Tsugawa

Čajka

et al. 2017

Mass Spectrometry Reviews

329

320

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Tandem mass spectral library search (MS/MS) is the fastest way to correctly annotate MS/MS spectra from screening small molecules in fields such as environmental analysis, drug screening, lipid analysis, and metabolomics. The confidence in MS/MS-based annotation of chemical structures is impacted by instrumental settings and requirements, data acquisition modes including data-dependent and data-independent methods, library scoring algorithms, as well as post-curation steps. We critically discuss parameters that influence search results, such as mass accuracy, precursor ion isolation width, intensity thresholds, centroiding algorithms, and acquisition speed. A range of publicly and commercially available MS/MS databases such as NIST, MassBank, MoNA, LipidBlast, Wiley MSforID, and METLIN are surveyed. In addition, software tools including NIST MS Search, MS-DIAL, Mass Frontier, SmileMS, Mass++, and XCMS to perform fast MS/MS search are discussed. MS/MS scoring algorithms and challenges during compound annotation are reviewed. Advanced methods such as the in silico generation of tandem mass spectra using quantum chemistry and machine learning methods are covered. Community efforts for curation and sharing of tandem mass spectra that will allow for faster distribution of scientific discoveries are discussed.

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Enhancing the Power of Liquid Chromatography–Mass Spectrometry-Based Urine Metabolomics in Negative Ion Mode by Optimization of the Additive

Cited by 42 publications

References 21 publications

Direct Identification of Tyrosine Sulfation by using Ultraviolet Photodissociation Mass Spectrometry

Direct Identification of Tyrosine Sulfation by using Ultraviolet Photodissociation Mass Spectrometry

Urinary Loss of Tricarboxylic Acid Cycle Intermediates As Revealed by Metabolomics Studies: An Underlying Mechanism to Reduce Lipid Accretion by Whey Protein Ingestion?

Identification of small molecules using accurate mass MS/MS search

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