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Liquid Chromatography Techniques in Lipidomics Research

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Abstract

Lipids represent a very diverse group of compounds with a high variety of physicochemical properties determining their functional activities. For omics-wide identification of lipid species from complex biological samples, several crucial analytical steps including extraction, chromatographic separation and mass spectrometry analysis need to be carefully considered and validated. Here we review applications of three main chromatography techniques—reversed phase, normal phase and hydrophilic interaction liquid chromatography—for analysis of complex natural lipidomes aiming to uncover the diversity of lipid species. To correlate lipid separation with their physicochemical properties, lipid chemical space was reconstructed and used to explain principles underlying different chromatographic techniques. Furthermore, examples of available methods for analysis of complex natural lipidomes characterized by high diversity and dynamic range of lipid concentrations are illustrated for adipose tissue lipidomics.

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Abbreviations

1,2-DAG:

1,2-Diacylglycerol

1,3-DAG:

1,3-Diacylglycerol

1-LPC:

1-Lysophosphatidylcholine

1-LPG:

1-Lysophosphatidylglycerol

1-MAG:

1-Monoacylglycerol

2-LPC:

2-Lysophosphatidylcholine

2-LPE:

2-Lysophosphatidylethanolamine

2-LPG:

2-Lysophosphatidylglycerol

Ag-HPLC:

Argentation/silver ion HPLC

AmFm:

Ammonium formate

AmOAc:

Ammonium acetate

ASA:

Accessible surface area

ASG:

Acylated steryl glycosides

AT:

Adipose tissue

BEH:

Ethylene bridged hybrid

C18:

Octadecyl derivatized silica

C1P:

Ceramide-1-phosphate

C30:

Triacontanyl derivatized silica

C4:

Butyl derivatized silica

C8:

Octyl derivatized silica

CE:

Cholesteryl esters

Cer:

Ceramide

Cer-NOH:

Non-hydroxy fatty acid ceramides

Cer-OH:

Hydroxy fatty acid ceramide

CHCl3:

Chloroform

Chol:

Free cholesterol

CL:

Cardiolipin

CMNH:

Charge modulated hydroxyethyl amide HILIC

CN:

Cyanopropyl

CS:

Cholesteryl sulfate

cyHex:

Cyclohexane

DAG:

Diacylglycerol

DCM:

Dichloromethane

DDA:

Data-dependent acquisition

DGCC:

Diacylglycerol-carboxymethylcholine

DGDG:

Digalactosyldiacylglycerols

DGTS:

Diacylglycerol-trimethylhomoserin

dhCer1P:

Dihydro-ceramide-1-phosphate

Dimet-SPH:

Dimethyl-sphingosine

Diol:

Dihydroxy-propyl

ECN:

Equivalent carbon number

ESI:

Electrospray ionization

EtOAc:

Ethyl acetate

EtOH:

Ethanol

FA:

Formic acid

FAME:

Fatty acid methyl esters

FFA:

Free fatty acid

FPP:

Fully porous particles

GalCer:

Galactosylceramide

GalCer-NOH:

Non-hydroxy galactosylceramide

GlcCer:

Glucosylceramide

GM1:

Ganglioside

H2O:

Water

H3PO4 :

Phosphoric acid

Hept:

Heptane

Hex:

Hexane

HexCer:

Hexosylceramide

HILIC:

Hydrophilic interaction chromatography

HOAc:

Acetic acid

i-Hex:

Iso-hexane

i-Oct:

Iso-octane

IPA:

Isopropanol

IPC:

Inositol-phosphoceramide

LAA:

Lipoamino acid

LacCer:

Lactosylceramide

LC–MS:

Liquid chromatography–mass spectrometry

LPA:

Lysophosphatidic acid

LPA:

Lysophosphatidic acid

LPC:

Lyso-phosphatidylcholine

LPE:

Lysophosphatidylethanolamine

LPG:

Lysophosphatidylglycerol

LPI:

Lysophosphatidylinositol

MAG:

Monoacylglycerol

MB:

Mobile phase

MD:

Molecular descriptor

MeCN:

Acetonitrile

MeDAG:

Monoalkyl diacylglycerol

MeOH:

Methanol

MGDG:

Monogalatosyldiacylglycerols

MS:

Mass spectrometry

MTBE:

Methyl-tert-butyl-ether

NAPE:

N-acylphosphatidylethanolamine

NH3 :

Ammonia

NMM:

N-methylmorpholine

NPC:

Normal phase chromatography

PA:

Phosphatidic acid

PC:

Phosphatidylcholine

PC1:

Principal component 1

PC2:

Principal component 2

PCA:

Principal component analysis

PE:

Phosphatidylethanolamine

PG:

Phosphatidylglycerol

Phyto-SPH:

Phytosphingosine

PI:

Phosphatidylinositol

P-PC:

Plasmalogen-phosphatidylcholine

P-PE:

Plasmalogen-phosphtadiylethanolamine

PS:

Phosphatidylserine

PVA:

Polyvinyl alcohol

RP:

Reversed phase

RPC:

Reversed phase chromatography

S1P:

Sphingosine-1-phosphate

Sa1P:

Sphinganine-1-phosphate

SCP:

Solid core particles

SFC:

Supercritical fluid chromatography

SG:

Steryl glycosides

Si:

Silica

Si-H:

Silica hydride

SM:

Sphingomyelin

SP:

Stationary phase

SPA:

Sphinganine

SPH:

Sphingosine

SPH:

Sphingosine

SQ:

Squalene

SQDG:

Sulfoqunovosyl diacylglycerol

ST:

Sulfatide

TAG:

Triacylglycerols

TEA:

Trimethylamine

TFA:

Trifluoro acetic acid

THF:

Tetrahydrofurane

Trimet-SPH:

Trimethyl-sphingosine

VAT:

Visceral adipose tissue

WAT:

White adipose tissue

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Funding

Financial support from the German Federal Ministry of Education and Research (BMBF) within the framework of the e:Med research and funding concept for SysMedOS project (to MF) and EU H2020 funded project MASSTRPLAN (Grant number 675132; to MF) are gratefully acknowledged.

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Authors and Affiliations

  1. Institut für Bioanalytische Chemie, Faculty of Chemistry and Mineralogy, Biotechnologisch-Biomedizinisches Zentrum, Leipzig University, Deutscher Platz 5, 04103, Leipzig, Germany

    Mike Lange, Zhixu Ni, Angela Criscuolo & Maria Fedorova

  2. Center for Biotechnology and Biomedicine, University of Leipzig, Leipzig, Germany

    Mike Lange, Zhixu Ni, Angela Criscuolo & Maria Fedorova

  3. Thermo Fisher Scientific (Bremen) GmbH, Hanna-Kunath-Str. 11, 28199, Bremen, Germany

    Angela Criscuolo

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  1. Mike Lange
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  2. Zhixu Ni
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  3. Angela Criscuolo
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  4. Maria Fedorova
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Correspondence to Maria Fedorova.

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Published in Chromatographia’s 50th Anniversary Commemorative Issue.

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Lange, M., Ni, Z., Criscuolo, A. et al. Liquid Chromatography Techniques in Lipidomics Research. Chromatographia 82, 77–100 (2019). https://doi.org/10.1007/s10337-018-3656-4

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  • DOI: https://doi.org/10.1007/s10337-018-3656-4

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