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Updated: Jun 17, 2026

Untargeted Metabolomics from Biological Sources Using Ultraperformance Liquid Chromatography-High Resolution Mass Spectrometry (UPLC-HRMS)
Published on: May 20, 2013
Chemical space blind spots: how chromatographic selectivity dictates chemical measurability and coverage of LC-HRMS
Lapo Renai1, Jens Heemskerk1, Frederic Béen2,3
1Van't Hoff Institute for Molecular Sciences (HIMS), University of Amsterdam, 1090 GD, Amsterdam, The Netherlands. l.renai@uva.nl.
Abstract:
Liquid chromatography high-resolution mass spectrometry enables broad chemical detection by comprehensive accurate mass to charge ratio measurement of the components in complex samples; yet, analytical design constrains chemical space measurability. A meta-analysis of 236 methods and over 75 000 measured compounds reveals strong convergence toward reversed-phase separations, limiting the coverage of sample chemical diversity. This "measurability trap" narrows the observable chemical space and can lead to the underrepresentation of many environmentally and biologically relevant compounds.
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