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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
Review

Abstract

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.

Keywords

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 

Abbreviations

ADP

Adenosine diphosphate

AMP

Adenosine monophosphate

ATP

Adenosine triphosphate

CHO

Chinese hamster ovary cells

CSF

Cerebrospinal fluid

DBS

Dried blood spot or dried biofluid spot

EDTA

Ethylenediaminetetraacetic acid

ESI

Electrospray ionization

GC–MS

Gas chromatography–mass spectrometry

HILIC

Hydrophilic interaction chromatography

HPLC

High-performance liquid chromatography

HUSERMET

Human serum metabolome project

LC–MS

Liquid chromatography–mass spectrometry

NAD

Nicotinamide adenine dinucleotide

NADH

Reduced nicotinamide adenine dinucleotide

NMR

Nuclear magnetic resonance

PBS

Phosphate-buffered saline

PCA

Principal-component analysis

RSD

Relative standard deviation

SPE

Solid-phase extraction

SPME

Solid-phase microextraction

TFC

Turbulent-flow chromatography

UHPLC

Ultra-high-performance liquid chromatography

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

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

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