Mass spectral fragmentation of trimethylsilylated small molecules

Zijuan Lai, Oliver Fiehn

Research output: Contribution to journalArticle

13 Citations (Scopus)

Abstract

Mass spectrometry-based untargeted metabolomics detects many peaks that cannot be identified. While advances have been made for automatic structure annotations in LC-electrospray-MS/MS, no open source solutions are available for hard electron ionization used in GC-MS. In metabolomics, most compounds bear moieties with acidic protons, for example, amino, hydroxyl, or carboxyl groups. Such functional groups increase the boiling points of metabolites too much for use in GC-MS. Hence, in GC-MS-focused metabolomics, derivatization of these groups is essential and has been employed since the 1960s. Specifically, trimethylsilylation is known as mild and universal method for GC-MS analysis. Here, we comprehensively compile accurate mass fragmentation rules and pathways of trimethylsilylated small molecules from 80 research articles over the past 5 decades, including diagnostic fragment ions, neutral losses, and typical ion ratios, for alcohols, carboxylic acids, amines, amino acids, sugars, steroids, thiols, and phosphates. These fragmentation rules were subsequently validated by specificity and sensitivity assessments using the NIST 14 nominal mass library and a new in-house GC-QTOF MS library containing 589 accurate mass spectra. From 556 tested fragmentation patterns, 228 rules yielded true positive hits within 4mDa mass accuracy. These rules can be applied to assign substructures for mass spectra computation and unknown identification.

Original languageEnglish (US)
JournalMass Spectrometry Reviews
DOIs
StateAccepted/In press - 2016

Fingerprint

Metabolomics
fragmentation
Libraries
Molecules
Ions
Amino Sugars
molecules
Boiling point
mass spectra
Metabolites
Carboxylic Acids
Sulfhydryl Compounds
Sugars
Hydroxyl Radical
Functional groups
Ionization
Amines
Mass spectrometry
Protons
Mass Spectrometry

Keywords

  • Cheminformatics
  • Gas chromatography-mass spectrometry
  • Software
  • Spectra simulation
  • Structure elucidation

ASJC Scopus subject areas

  • Analytical Chemistry
  • Biochemistry, Genetics and Molecular Biology(all)
  • Condensed Matter Physics
  • Spectroscopy

Cite this

Mass spectral fragmentation of trimethylsilylated small molecules. / Lai, Zijuan; Fiehn, Oliver.

In: Mass Spectrometry Reviews, 2016.

Research output: Contribution to journalArticle

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