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

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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.

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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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    Dajana Vuckovic

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Vuckovic, D. Current trends and challenges in sample preparation for global metabolomics using liquid chromatography–mass spectrometry. Anal Bioanal Chem 403, 1523–1548 (2012). https://doi.org/10.1007/s00216-012-6039-y

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