Metabolite identification and quantitation in LC-MS/MS-based metabolomics

Abstract

Metabolomics aims at detection and quantitation of all metabolites in biological samples. The presence of metabolites with a wide variety of physicochemical properties and different levels of abundance challenges existing analytical platforms used for identification and quantitation of metabolites. Significant efforts have been made to improve analytical and computational methods for metabolomics studies. This review focuses on the use of liquid chromatography with tandem mass spectrometry (LC-MS/MS) for quantitative and qualitative metabolomics studies. It illustrates recent developments in computational methods for metabolite identification, including ion annotation, spectral interpretation and spectral matching. We also review selected reaction monitoring and high-resolution MS for metabolite quantitation. We discuss current challenges in metabolite identification and quantitation as well as potential solutions.

Quasi-targeted analysis of hydroxylation-related metabolites of polycyclic aromatic hydrocarbons in human urine by liquid chromatography–mass spectrometry

“…Moreover, it can also be used for tentatively untargeted metabolite identification of xenobiotic compounds via precursor ion scan (PIS), product ion scan, neutral loss scan (NLS), and MRM modes [13]. Some metabolites, e.g., phase II metabolites, can generate chromatographic peaks in MRM channels set for monitoring their parent compounds [14,15].…”

“…LC equipped with high resolution mass spectrometry (LC-HRMS), e.g., LC quadrupole time-of-flight MS (LC-QTOF-MS) and LC-Q-Orbitrap-MS, operated in full scan mode has been widely used for untargeted metabolite identification due to its accurate mass determination [13,17]. However, data mining processes are complex and time-consuming, let alone potential false positives [18,19].…”

Development of Zwitterionic Hydrophilic Liquid Chromatography (ZICⓇHILIC-MS) Metabolomics Method for Shotgun Analysis of Human Urine

“…The majority of urinary analytes are polar in nature, hence high performance liquid chromatography-mass spectrometry (HPLC-MS) based metabolomics is widely used for urinary analyses [12][13][14]. Commonly, reversed phase high performance liquid chromatography (RP HPLC) is employed for urinary metabolomics studies due to its versatile nature.…”

Development of nanoelectrospray high resolution isotope dilution mass spectrometry for targeted quantitative analysis of urinary metabolites: application to population profiling and clinical studies

“…[12][13][14][15] At present, metabonomic studies benefit from various available MS technologies including different ionization techniques and mass analyzers with different resolving power and mass accuracy. LC separation followed by triple quadrupole-based multiple reaction monitoring (MRM) is the leading choice for targeted metabolite quantification.…”

“…LC separation followed by triple quadrupole-based multiple reaction monitoring (MRM) is the leading choice for targeted metabolite quantification. 14 This approach has been considered as a "gold standard" for absolute quantification of small molecules due to its sensitivity and specificity. However, the information provided by this approach is limited to the targeted metabolites and the other metabolites in the biofluid remain undetected.…”