Analytical and Bioanalytical Chemistry

, Volume 403, Issue 6, pp 1523–1548 | Cite as

Current trends and challenges in sample preparation for global metabolomics using liquid chromatography–mass spectrometry

  • Dajana Vuckovic


The choice of sample-preparation method is extremely important in metabolomic studies because it affects both the observed metabolite content and biological interpretation of the data. An ideal sample-preparation method for global metabolomics should (i) be as non-selective as possible to ensure adequate depth of metabolite coverage; (ii) be simple and fast to prevent metabolite loss and/or degradation during the preparation procedure and enable high-throughput; (iii) be reproducible; and (iv) incorporate a metabolism-quenching step to represent true metabolome composition at the time of sampling. Despite its importance, sample preparation is often an overlooked aspect of metabolomics, so the focus of this review is to explore the role, challenges, and trends in sample preparation specifically within the context of global metabolomics by liquid chromatography–mass spectrometry (LC–MS). This review will cover the most common methods including solvent precipitation and extraction, solid-phase extraction and ultrafiltration, and discuss how to improve analytical quality and metabolite coverage in metabolomic studies of biofluids, tissues, and mammalian cells. Recent developments in this field will also be critically examined, including in vivo methods, turbulent-flow chromatography, and dried blood spot sampling.


Metabolomics Untargeted metabolite profiling Sample preparation Metabolism quenching Solvent extraction Ultrafiltration In vivo sampling Dried blood spots Method development Liquid chromatography–mass spectrometry (LC–MS) Mammalian cells Tissue 



Adenosine diphosphate


Adenosine monophosphate


Adenosine triphosphate


Chinese hamster ovary cells


Cerebrospinal fluid


Dried blood spot or dried biofluid spot


Ethylenediaminetetraacetic acid


Electrospray ionization


Gas chromatography–mass spectrometry


Hydrophilic interaction chromatography


High-performance liquid chromatography


Human serum metabolome project


Liquid chromatography–mass spectrometry


Nicotinamide adenine dinucleotide


Reduced nicotinamide adenine dinucleotide


Nuclear magnetic resonance


Phosphate-buffered saline


Principal-component analysis


Relative standard deviation


Solid-phase extraction


Solid-phase microextraction


Turbulent-flow chromatography


Ultra-high-performance liquid chromatography


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© Springer-Verlag 2012

Authors and Affiliations

  1. 1.Donnelly Centre for Cellular and Biomolecular ResearchUniversity of TorontoTorontoCanada

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