ArticleJournal of proteome research2018
Trace Phosphate Improves ZIC-pHILIC Peak Shape, Sensitivity, and Coverage for Untargeted Metabolomics.
Article in Journal of proteome research, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
20 citing papers in PubMed.
- Low-Temperature HILIC Provides Enhanced Separations and Stability for LC-MS-Based Metabolomics.Journal of proteome research · 2026Article
- Enhancing metabolite coverage using dedicated mobile phases for individual polarity modes in HILIC-MS.Analytical and bioanalytical chemistry · 2026Article
- NFIA regulates articular chondrocyte fatty acid metabolism and joint homeostasis.Science translational medicine · 2025Article
- From Complexity to Clarity: Expanding Metabolome Coverage With Innovative Analytical Strategies.Journal of separation science · 2025Review
- Distinguishing Artifactual Fatty Acid Dimers from Fatty Acid Esters of Hydroxy Fatty Acids in Untargeted LC-MS Pipelines.Methods in molecular biology (Clifton, N.J.) · 2025Article
- Article
- Cytosolic and mitochondrial NADPH fluxes are independently regulated.Nature chemical biology · 2023Article
- Mitochondrial citrate metabolism and efflux regulate BeWo differentiation.Scientific reports · 2023Article
- 1,2-Current issues in molecular biology · 2023Article
- Interrogating in vivo T-cell metabolism in mice using stable isotope labeling metabolomics and rapid cell sorting.Nature protocols · 2021Article
- Urinary 2-Hydroxyglutarate Enantiomers Are Markedly Elevated in a Murine Model of Type 2 Diabetic Kidney Disease.Metabolites · 2021Article
- Isotope tracing in adult zebrafish reveals alanine cycling between melanoma and liver.Cell metabolism · 2021Article
- DecoID improves identification rates in metabolomics through database-assisted MS/MS deconvolution.Nature methods · 2021Article
- Targeting unique biological signals on the fly to improve MS/MS coverage and identification efficiency in metabolomics.Analytica chimica acta · 2021Article
- Recurrent Topics in Mass Spectrometry-Based Metabolomics and Lipidomics-Standardization, Coverage, and Throughput.Analytical chemistry · 2021Review
- Glutaminase Inhibitors Induce Thiol-Mediated Oxidative Stress and Radiosensitization in Treatment-Resistant Cervical Cancers.Molecular cancer therapeutics · 2020Article
- Chemical Discovery in the Era of Metabolomics.Journal of the American Chemical Society · 2020Review
- In-Source CID Ramping and Covariant Ion Analysis of Hydrophilic Interaction Chromatography Metabolomics.Analytical chemistry · 2020Article
- Article
- Transport-exclusion pharmacology to localize lactate dehydrogenase activity within cells.Cancer & metabolism · 2018Article
Corrections and comments
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Authors and funding
5 authors.
Funding
Abstract
Existing hydrophilic interaction liquid chromatography (HILIC) methods, considered individually, each exhibit poor chromatographic performance for a substantial fraction of polar metabolites. In addition to limiting metabolome coverage, such deficiencies also complicate automated data processing. Here we show that some of these analytical challenges can be addressed for the ZIC-pHILIC, a zwitterionic stationary phase commonly used in metabolomics, with the addition of trace levels of phosphate. Specifically, micromolar phosphate extended metabolome coverage by hundreds of credentialed features, improved peak shapes, and reduced peak-detection errors during informatic processing. Although the addition of high levels of phosphate (millimolar) as a HILIC mobile phase buffer has been explored previously, such concentrations interfere with mass spectrometric (MS) detection. We show that using phosphate as a trace additive at micromolar concentrations improves analysis by electrospray MS, increasing signal for a diverse set of polar standards. Given the small amount of phosphate needed, comparable chromatographic improvements were also achieved by direct addition of phosphate to the sample during reconstitution. Our results suggest that defects in ZIC-pHILIC performance are predominantly driven by electrostatic interactions, which can be modulated by phosphate. These findings constitute both a methodological improvement for untargeted metabolomics and an advance in our understanding of the mechanisms limiting HILIC coverage.
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