Liquid Chromatography Techniques in Lipidomics Research

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.

Graphical Abstract

This is a preview of subscription content, log in to check access.

Fig. 1
Fig. 2
Fig. 3
Fig. 4
Fig. 5

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

References

  1. 1.

    Fahy E et al (2009) Update of the LIPID MAPS comprehensive classification system for lipids. J Lipid Res 50:S9–S14

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  2. 2.

    van Meer G, Voelker DR, Feigenson GW (2008) Membrane lipids: where they are and how they behave. Nat Rev Mol Cell Biol 9:112–124

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  3. 3.

    Karantonis HC, Nomikos T, Demopoulos CA (2009) Triacylglycerol metabolism. Curr Drug Targets 10:302–319

    Article  CAS  PubMed  Google Scholar 

  4. 4.

    Ahmadian M, Duncan RE, Jaworski K, Sarkadi-Nagy E, Sul HS (2007) Triacylglycerol metabolism in adipose tissue. Future Lipidol 2:229–237

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  5. 5.

    Wymann MP, Schneiter R (2008) Lipid signalling in disease. Nat Rev Mol Cell Biol 9:162–176

    Article  CAS  PubMed  Google Scholar 

  6. 6.

    Masoodi M, Kuda O, Rossmeisl M, Flachs P, Kopecky J (2015) Lipid signaling in adipose tissue: connecting inflammation and metabolism. Biochim Biophys Acta Mol Cell Biol Lipids 1851:503–518

  7. 7.

    Yetukuri L, Ekroos K, Vidal-Puig A, Oresic M (2008) Informatics and computational strategies for the study of lipids. Mol Biosyst 4:121–127

    Article  CAS  PubMed  Google Scholar 

  8. 8.

    Řezanka T, Kolouchová I, Gharwalová L, Palyzová A, Sigler K (2018) Lipidomic analysis: from archaea to mammals. Lipids 53:5–25

    Article  CAS  PubMed  Google Scholar 

  9. 9.

    Rampler E et al (2018) A novel lipidomics workflow for improved human plasma identification and quantification using RPLC-MSn methods and isotope dilution strategies. Anal Chem 90:6494–6501

    Article  CAS  PubMed  Google Scholar 

  10. 10.

    Gao X et al (2012) A reversed-phase capillary ultra-performance liquid chromatography–mass spectrometry (UPLC–MS) method for comprehensive top-down/bottom-up lipid profiling. Anal Bioanal Chem 402:2923–2933

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  11. 11.

    Peng B et al (2018) Identification of key lipids critical for platelet activation by comprehensive analysis of the platelet lipidome. Blood. https://doi.org/10.1182/blood-2017-12-822890

    Article  PubMed  PubMed Central  Google Scholar 

  12. 12.

    Carvalho M et al (2012) Effects of diet and development on the Drosophila lipidome. Mol Syst Biol 8:600

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  13. 13.

    Hummel J et al (2011) Ultra performance liquid chromatography and high resolution mass spectrometry for the analysis of plant lipids. Front Plant Sci 2:54

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  14. 14.

    Schwudke D, Liebisch G, Herzog R, Schmitz G, Shevchenko A (2007) Shotgun lipidomics by tandem mass spectrometry under data-dependent acquisition control. Methods Enzymol 433:175–191

    Article  CAS  PubMed  Google Scholar 

  15. 15.

    Schwudke D et al (2006) Lipid profiling by multiple precursor and neutral loss scanning driven by the data-dependent acquisition. Anal Chem 78:585–595

    Article  CAS  PubMed  Google Scholar 

  16. 16.

    Tumanov S, Kamphorst JJ (2017) Recent advances in expanding the coverage of the lipidome. Curr Opin Biotechnol 43:127–133

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  17. 17.

    Cajka T, Fiehn O (2014) Comprehensive analysis of lipids in biological systems by liquid chromatography–mass spectrometry. Trends Anal Chem 61:192–206

    Article  CAS  Google Scholar 

  18. 18.

    Instant JChem 18.8.0. (2018) Instant JChem was used for the prediction of properties from lipid structures. http://www.chemaxon.com. Accessed 1 Aug 2018

  19. 19.

    Dorsey JG, Cooper WT (1994) Retention mechanisms of bonded-phase liquid chromatography. Anal Chem 66:857A–867A

    Article  CAS  PubMed  Google Scholar 

  20. 20.

    Vailaya A (2005) Fundamentals of reversed phase chromatography: thermodynamic and exothermodynamic treatment. J Liq Chromatogr Relat Technol 28:965–1054

    Article  CAS  Google Scholar 

  21. 21.

    Layne J (2002) Characterization and comparison of the chromatographic performance of conventional, polar-embedded, and polar-endcapped reversed-phase liquid chromatography stationary phases. J Chromatogr A 957:149–164

    Article  CAS  PubMed  Google Scholar 

  22. 22.

    Ovčačíková M, Lísa M, Cífková E, Holčapek M (2016) Retention behavior of lipids in reversed-phase ultrahigh-performance liquid chromatography-electrospray ionization mass spectrometry. J Chromatogr A 1450:76–85

    Article  CAS  PubMed  Google Scholar 

  23. 23.

    Háková E et al (2015) Localization of double bonds in triacylglycerols using high-performance liquid chromatography/atmospheric pressure chemical ionization ion-trap mass spectrometry. Anal Bioanal Chem 407:5175–5188

    Article  CAS  PubMed  Google Scholar 

  24. 24.

    Nakanishi H, Iida Y, Shimizu T, Taguchi R (2010) Separation and quantification of sn-1 and sn-2 fatty acid positional isomers in phosphatidylcholine by RPLC-ESIMS/MS. J Biochem 147:245–256

    Article  CAS  PubMed  Google Scholar 

  25. 25.

    Witting M, Maier TV, Garvis S, Schmitt-Kopplin P (2014) Optimizing a ultrahigh pressure liquid chromatography-time of flight-mass spectrometry approach using a novel sub-2 µm core-shell particle for in depth lipidomic profiling of Caenorhabditis elegans. J Chromatogr A 1359:91–99

    Article  CAS  PubMed  Google Scholar 

  26. 26.

    Bird SS, Marur VR, Stavrovskaya IG, Kristal BS (2012) Separation of cistrans phospholipid isomers using reversed phase LC with high resolution MS detection. Anal Chem 84:5509–5517

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  27. 27.

    Narváez-rivas M, Zhang Q (2016) Comprehensive untargeted lipidomic analysis using core–shell C30 particle column and high field orbitrap mass spectrometer. J Chromatogr A 1440:123–134

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  28. 28.

    Norman HA, St John JB (1986) Separation and quantitation of molecular species of plant phosphatidylcholine by high-performance liquid chromatography with flame ionization detection. J Lipid Res 27:1104–1107

    CAS  PubMed  Google Scholar 

  29. 29.

    Lee C, Fisher SK, Agranoff BW, Hajra AK (1991) Quantitative analysis of molecular species of diacylglycerol and phosphatidate formed upon muscarinic receptor activation of human SK-N-SH neuroblastoma cells. J Biol Chem 266:22837–22846

    CAS  PubMed  Google Scholar 

  30. 30.

    Ousley AH, Morell P (1992) Individual molecular species of phosphatidylcholine and phosphatidylethanolamine in myelin turn over at different rates. J Biol Chem 267:10362–10369

    CAS  PubMed  Google Scholar 

  31. 31.

    Rainville PD, Stumpf CL, Shockcor JP, Plumb RS, Nicholson JK (2007) Novel application of reversed-phase UPLC-oaTOF-MS for lipid analysis in complex biological mixtures: a new tool for lipidomics. J Proteome Res. 6(2):552–558. https://doi.org/10.1021/pr060611b

    CAS  Article  PubMed  Google Scholar 

  32. 32.

    Ogiso H, Suzuki T, Taguchi R (2008) Development of a reverse-phase liquid chromatography electrospray ionization mass spectrometry method for lipidomics, improving detection of phosphatidic acid and phosphatidylserine. Anal Biochem 375:124–131

    Article  CAS  PubMed  Google Scholar 

  33. 33.

    Hu C et al (2008) RPLC-ion-trap-FTMS method for lipid profiling of plasma: method validation and application to p53 mutant mouse model. J Proteome Res 7:4982–4991

    Article  CAS  PubMed  Google Scholar 

  34. 34.

    Le Grandois J et al (2009) Investigation of natural phosphatidylcholine sources: separation and identification by liquid chromatography–electrospray ionization–tandem mass spectrometry (LC–ESI–MS2) of molecular species. J Agric Food Chem 57:6014–6020

    Article  CAS  PubMed  Google Scholar 

  35. 35.

    Vale P (2010) Profiles of fatty acids and 7-O-acyl okadaic acid esters in bivalves: can bacteria be involved in acyl esterification of okadaic acid? Comp Biochem Physiol C Toxicol Pharmacol 151:18–24

    Article  CAS  PubMed  Google Scholar 

  36. 36.

    Sandra K, dos Santos Pereira A, Vanhoenacker G, David F, Sandra P (2010) Comprehensive blood plasma lipidomics by liquid chromatography/quadrupole time-of-flight mass spectrometry. J Chromatogr A 1217:4087–4099

    Article  CAS  PubMed  Google Scholar 

  37. 37.

    Bird SS, Marur VR, Sniatynski MJ, Greenberg HK, Kristal BS (2011) Lipidomics profiling by high-resolution LC–MS and high-energy collisional dissociation fragmentation: focus on characterization of mitochondrial cardiolipins and monolysocardiolipins. Anal Chem 83:940–949

    Article  CAS  PubMed  Google Scholar 

  38. 38.

    Bird SS, Marur VR, Sniatynski MJ, Greenberg HK, Kristal BS (2011) Serum lipidomics profiling using LC–MS and high-energy collisional dissociation fragmentation: focus on triglyceride detection and characterization. Anal Chem 83:6648–6657

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  39. 39.

    Gruber F, Bicker W, Oskolkova OV, Tschachler E, Bochkov VN (2012) A simplified procedure for semi-targeted lipidomic analysis of oxidized phosphatidylcholines induced by UVA irradiation. J Lipid Res 53:1232–1242

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  40. 40.

    Yamada T et al (2013) Development of a lipid profiling system using reverse-phase liquid chromatography coupled to high-resolution mass spectrometry with rapid polarity switching and an automated lipid identification software. J Chromatogr A 1292:211–218

    Article  CAS  PubMed  Google Scholar 

  41. 41.

    Bird SS, Marur VR, Stavrovskaya IG, Kristal BS (2013) Qualitative characterization of the rat liver mitochondrial lipidome using LC–MS profiling and high energy collisional dissociation (HCD) all ion fragmentation. Metabolomics 9:67–83

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  42. 42.

    Gallart-Ayala H et al (2013) Versatile lipid profiling by liquid chromatography-high resolution mass spectrometry using all ion fragmentation and polarity switching. Preliminary application for serum samples phenotyping related to canine mammary cancer. Anal Chim Acta 796:75–83

    Article  CAS  PubMed  Google Scholar 

  43. 43.

    Wang J-R et al (2014) Improved sphingolipidomic approach based on ultra-high performance liquid chromatography and multiple mass spectrometries with application to cellular neurotoxicity. Anal Chem 86:5688–5696

    Article  CAS  PubMed  Google Scholar 

  44. 44.

    Martano C, Mugoni V, Dal Bello F, Santoro MM, Medana C (2015) Rapid high performance liquid chromatography–high resolution mass spectrometry methodology for multiple prenol lipids analysis in zebrafish embryos. J Chromatogr A 1412:59–66

    Article  CAS  PubMed  Google Scholar 

  45. 45.

    Zou J et al (2015) Evaluation of the change in sphingolipids in the human multiple myeloma cell line U266 and gastric cancer cell line MGC-803 treated with arsenic trioxide. J Chromatogr B Analyt Technol Biomed Life Sci 1004:98–107

    Article  CAS  PubMed  Google Scholar 

  46. 46.

    Mi J-N, Wang J-R, Jiang Z-H (2016) Quantitative profiling of sphingolipids in wild Cordyceps and its mycelia by using UHPLC-MS. Sci Rep 6:20870

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  47. 47.

    Triebl A, Trötzmüller M, Hartler J, Stojakovic T, Köfeler HC (2017) Lipidomics by ultrahigh performance liquid chromatography-high resolution mass spectrometry and its application to complex biological samples. J Chromatogr B Analyt Technol Biomed Life Sci 1053:72–80

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  48. 48.

    Ballschmiter K, Wößner M (1998) Recent developments in adsorption liquid chromatography (NP-HPLC). Fresenius J Anal Chem 361:743–755

    Article  CAS  Google Scholar 

  49. 49.

    Christie WW, Urwin RA (1995) Separation of lipid classes from plant tissues by high performance liquid chromatography on chemically bonded stationary phases. J High Resolut Chromatogr 18:97–100

    Article  CAS  Google Scholar 

  50. 50.

    Olsson P, Holmbäck J, Herslöf B (2012) Separation of lipid classes by HPLC on a cyanopropyl column. Lipids 47:93–99

    Article  CAS  PubMed  Google Scholar 

  51. 51.

    Nordbäck J, Lundberg E, Christie WW (1998) Separation of lipid classes from marine particulate material by HPLC on a polyvinyl alcohol-bonded stationary phase using dual-channel evaporative light-scattering detection. Mar Chem 60:165–175

    Article  Google Scholar 

  52. 52.

    Deschamps FS, Chaminade P, Ferrier D, Baillet A (2001) Assessment of the retention properties of poly(vinyl alcohol) stationary phase for lipid class profiling in liquid chromatography. J Chromatogr A 928:127–137

    Article  CAS  PubMed  Google Scholar 

  53. 53.

    Sommer U, Herscovitz H, Welty FK, Costello CE (2006) LC–MS-based method for the qualitative and quantitative analysis of complex lipid mixtures. J Lipid Res 47:804–814

    Article  CAS  PubMed  Google Scholar 

  54. 54.

    Sokol E et al (2013) Profiling of lipid species by normal-phase liquid chromatography, nanoelectrospray ionization, and ion trap-orbitrap mass spectrometry. Anal Biochem 443:88–96

    Article  CAS  PubMed  Google Scholar 

  55. 55.

    Mclaren DG et al (2011) An ultraperformance liquid chromatography method for the normal-phase separation of lipids. Anal Biochem 414:266–272

    Article  CAS  PubMed  Google Scholar 

  56. 56.

    Abreu S, Solgadi A, Chaminade P (2017) Optimization of normal phase chromatographic conditions for lipid analysis and comparison of associated detection techniques. J Chromatogr A 1514:54–71

    Article  CAS  PubMed  Google Scholar 

  57. 57.

    Arnoldsson KC, Kaufmann P (1994) Lipid class analysis by normal phase high performance liquid chromatography, development and optimization using multivariate methods. Chromatographia 38:317–324

    Article  CAS  Google Scholar 

  58. 58.

    Prache N, Abreu S, Sassiat P, Thiébaut D, Chaminade P (2016) Alternative solvents for improving the greenness of normal phase liquid chromatography of lipid classes. J Chromatogr A 1464:55–63

    Article  CAS  PubMed  Google Scholar 

  59. 59.

    Holčapek M et al (2015) Determination of nonpolar and polar lipid classes in human plasma, erythrocytes and plasma lipoprotein fractions using ultrahigh-performance liquid chromatography–mass spectrometry. J Chromatogr A 1377:85–91

    Article  CAS  PubMed  Google Scholar 

  60. 60.

    Hutchins PM, Barkley RM, Murphy RC (2008) Separation of cellular nonpolar neutral lipids by normal-phase chromatography and analysis by electrospray ionization mass spectrometry. J Lipid Res 49:804–813

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  61. 61.

    Donot F et al (2016) Rapid analysis and quantification of major neutral lipid species and free fatty acids by HPLC-ELSD from microalgae. Eur J Lipid Sci Technol 118:1550–1556

    Article  CAS  Google Scholar 

  62. 62.

    Gardner MS et al (2017) Simultaneous quantification of free cholesterol, cholesteryl esters, and triglycerides without ester hydrolysis by UHPLC separation and in-source collision induced dissociation coupled MS/MS. J Am Soc Mass Spectrom 28:2319–2329

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  63. 63.

    Perona JS, Ruiz-Gutierrez V (2004) Quantification of major lipid classes in human triacylglycerol-rich lipoproteins by high-performance liquid chromatography with evaporative light-scattering detection. J Sep Sci 27:653–659

    Article  CAS  PubMed  Google Scholar 

  64. 64.

    Jiang P, Lucy CA (2016) Coupling normal phase liquid chromatography with electrospray ionization mass spectrometry: strategies and applications. Anal Methods 8:6478–6488

    Article  Google Scholar 

  65. 65.

    Tavares KM et al (2016) Free tocopherols as chemical markers for Arabica coffee adulteration with maize and coffee by-products. Food Control 70:318–324

    Article  CAS  Google Scholar 

  66. 66.

    Nguyen HP, Schug KA (2008) The advantages of ESI-MS detection in conjunction with HILIC mode separations: fundamentals and applications. J Sep Sci 31:1465–1480

    Article  CAS  PubMed  Google Scholar 

  67. 67.

    Méndez A, Bosch E, Rosés M, Neue UD (2003) Comparison of the acidity of residual silanol groups in several liquid chromatography columns. J Chromatogr A 986:33–44

    Article  PubMed  Google Scholar 

  68. 68.

    McCalley DV, Neue UD (2008) Estimation of the extent of the water-rich layer associated with the silica surface in hydrophilic interaction chromatography. J Chromatogr A 1192:225–229

    Article  CAS  PubMed  Google Scholar 

  69. 69.

    Grumbach ES, Diehl DM, Neue UD (2008) The application of novel 1.7 µm ethylene bridged hybrid particles for hydrophilic interaction chromatography. J Sep Sci 31:1511–1518

    Article  CAS  PubMed  Google Scholar 

  70. 70.

    Wernisch S, Pennathur S (2016) Evaluation of coverage, retention patterns, and selectivity of seven liquid chromatographic methods for metabolomics. Anal Bioanal Chem 408:6079–6091

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  71. 71.

    Tang D-Q, Zou L, Yin X-X, Ong C (2016) N. HILIC-MS for metabolomics: an attractive and complementary approach to RPLC-MS. Mass Spectrom Rev 35:574–600

    Article  CAS  PubMed  Google Scholar 

  72. 72.

    Guo Y, Gaiki S (2011) Retention and selectivity of stationary phases for hydrophilic interaction chromatography. J Chromatogr A 1218:5920–5938

    Article  CAS  PubMed  Google Scholar 

  73. 73.

    Cífková E, Hájek R, Lísa M, HolĿapek M (2016) Hydrophilic interaction liquid chromatography–mass spectrometry of (lyso)phosphatidic acids, (lyso)phosphatidylserines and other lipid classes. J Chromatogr A 1439:65–73

    Article  CAS  PubMed  Google Scholar 

  74. 74.

    Vosse C, Wienken C, Cadenas C, Hayen H (2018) Separation and identification of phospholipids by hydrophilic interaction liquid chromatography coupled to tandem high resolution mass spectrometry with focus on isomeric phosphatidylglycerol and bis(monoacylglycero)phosphate. J Chromatogr A 1565:105–113

    Article  CAS  PubMed  Google Scholar 

  75. 75.

    Buszewski B, Noga S (2012) Hydrophilic interaction liquid chromatography (HILIC)—a powerful separation technique. Anal Bioanal Chem 402:231–247

    Article  CAS  PubMed  Google Scholar 

  76. 76.

    Zhu C et al (2012) An efficient hydrophilic interaction liquid chromatography separation of 7 phospholipid classes based on a diol column. J Chromatogr A 1220:26–34

    Article  CAS  PubMed  Google Scholar 

  77. 77.

    Hines KM, Herron J, Xu L (2017) Assessment of altered lipid homeostasis by HILIC-ion mobility-mass spectrometry-based lipidomics. J Lipid Res 58:809–819

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  78. 78.

    Lísa M, Cífková E, Holčapek M (2011) Lipidomic profiling of biological tissues using off-line two-dimensional high-performance liquid chromatography–mass spectrometry. J Chromatogr A 1218:5146–5156

    Article  CAS  PubMed  Google Scholar 

  79. 79.

    Anesi A, Guella G (2015) A fast liquid chromatography–mass spectrometry methodology for membrane lipid profiling through hydrophilic interaction liquid chromatography. J Chromatogr A 1384:44–52

    Article  CAS  PubMed  Google Scholar 

  80. 80.

    Pang L-Q, Liang Q-L, Wang Y-M, Ping L, Luo G-A (2008) Simultaneous determination and quantification of seven major phospholipid classes in human blood using normal-phase liquid chromatography coupled with electrospray mass spectrometry and the application in diabetes nephropathy. J Chromatogr B 869:118–125

    Article  CAS  Google Scholar 

  81. 81.

    Zheng L et al (2010) Profiling of lipids in leishmania donovani using hydrophilic interaction chromatography in combination with fourier transform mass spectrometry. Rapid Commun Mass Spectrom 24:2074–2082

    Article  CAS  PubMed  Google Scholar 

  82. 82.

    Reis A et al (2013) A comparison of five lipid extraction solvent systems for lipidomic studies of human LDL. J Lipid Res 54:1812–1824

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  83. 83.

    Scherer M, Schmitz G, Liebisch G, Schmitz G (2009) High-throughput analysis of sphingosine 1-phosphate, sphinganine 1-phosphate, and lysophosphatidic acid in plasma samples by liquid chromatography-tandem mass spectrometry. Clin Chem 55:1218–1222

    Article  CAS  PubMed  Google Scholar 

  84. 84.

    Cífková E et al (2015) Lipidomic differentiation between human kidney tumors and surrounding normal tissues using HILIC–HPLC/ESI–MS and multivariate data analysis. J Chromatogr B Analyt Technol Biomed Life Sci 1000:14–21

    Article  CAS  PubMed  Google Scholar 

  85. 85.

    Cascone A, Eerola S, Ritieni A, Rizzo A (2006) Development of analytical procedures to study changes in the composition of meat phospholipids caused by induced oxidation. J Chromatogr A 1120:211–220

    Article  CAS  PubMed  Google Scholar 

  86. 86.

    Wang S et al (2013) A novel stop-flow two-dimensional liquid chromatography–mass spectrometry method for lipid analysis. J Chromatogr A 1321:65–72

    Article  CAS  PubMed  Google Scholar 

  87. 87.

    Fei F, Bowdish DME, McCarry BE (2014) Comprehensive and simultaneous coverage of lipid and polar metabolites for endogenous cellular metabolomics using HILIC–TOF–MS. Anal Bioanal Chem 406:3723–3733

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  88. 88.

    Scherer M, Leuthäuser-Jaschinski K, Ecker J, Schmitz G, Liebisch G (2010) A rapid and quantitative LC–MS/MS method to profile sphingolipids. J Lipid Res 51:2001–2011

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  89. 89.

    Fauland A et al (2011) A comprehensive method for lipid profiling by liquid chromatography-ion cyclotron resonance mass spectrometry. J Lipid Res 52:2314–2322

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  90. 90.

    Řezanka T, Siristova L, Matoulková D, Sigler K (2011) Hydrophilic interaction liquid chromatography: ESI–MS/MS of plasmalogen phospholipids from Pectinatus bacterium. Lipids 46:765–780

    Article  CAS  PubMed  Google Scholar 

  91. 91.

    Lísa M (2017) Silver-ion liquid chromatography–mass spectrometry. Handb Adv Chromatogr Spectrom Tech. https://doi.org/10.1016/B978-0-12-811732-3.00004-2

    Article  Google Scholar 

  92. 92.

    Nikolova-Damyanova B, Christie WW (1992) Advances in lipid methodology, vol 1 (P. J. Barnes & Associates). The Oily Press, Bridgwater

    Google Scholar 

  93. 93.

    Nikolova-Damyanova B (2009) Retention of lipids in silver ion high-performance liquid chromatography: facts and assumptions. J Chromatogr A 1216:1815–1824

    Article  CAS  PubMed  Google Scholar 

  94. 94.

    Lísa M, Velínská H, Holčapek M (2009) Regioisomeric characterization of triacylglycerols using silver-Ion HPLC/MS and randomization synthesis of standards. Anal Chem 81:3903–3910

    Article  CAS  PubMed  Google Scholar 

  95. 95.

    François I, dos Santos Pereira A, Sandra P (2010) Considerations on comprehensive and off-line supercritical fluid chromatography × reversed-phase liquid chromatography for the analysis of triacylglycerols in fish oil. J Sep Sci 33:1504–1512

    Article  CAS  PubMed  Google Scholar 

  96. 96.

    Beccaria M et al (2015) Determination of the triacylglycerol fraction in fish oil by comprehensive liquid chromatography techniques with the support of gas chromatography and mass spectrometry data. Anal Bioanal Chem 407:5211–5225

    Article  CAS  PubMed  Google Scholar 

  97. 97.

    Danne-Rasche N, Coman C, Ahrends R, Nano (2018) LC/NSI MS refines lipidomics by enhancing lipid coverage, measurement sensitivity, and linear dynamic range. Anal Chem. https://doi.org/10.1021/acs.analchem.8b01275

    Article  PubMed  Google Scholar 

  98. 98.

    Pettitt TR, Dove SK, Lubben A, Calaminus SDJ, Wakelam, MJO (2006) Analysis of intact phosphoinositides in biological samples. J Lipid Res 47:1588–1596

    Article  CAS  PubMed  Google Scholar 

  99. 99.

    Knittelfelder OL, Weberhofer BP, Eichmann TO, Kohlwein SD, Rechberger GN (2014) A versatile ultra-high performance LC–MS method for lipid profiling. J Chromatogr B 951–952:119–128

    Article  CAS  Google Scholar 

  100. 100.

    Cífková E, Holčapek M, Lísa M (2013) Nontargeted lipidomic characterization of porcine organs using hydrophilic interaction liquid chromatography and off-line two-dimensional liquid chromatography–electrospray ionization mass spectrometry. Lipids 48:915–928

    Article  CAS  PubMed  Google Scholar 

  101. 101.

    Hu J et al (2013) Characterization and quantification of triacylglycerols in peanut oil by off-line comprehensive two-dimensional liquid chromatography coupled with atmospheric pressure chemical ionization mass spectrometry. J Sep Sci 36:288–300

    Article  CAS  PubMed  Google Scholar 

  102. 102.

    Walczak J, Bocian S, Buszewski B (2015) Two-dimensional high performance liquid chromatography–mass spectrometry for phosphatidylcholine analysis in egg yolk. Food Anal Methods 8:661–667

    Article  Google Scholar 

  103. 103.

    Narváez-Rivas M, Vu N, Chen G-Y, Zhang Q (2017) Off-line mixed-mode liquid chromatography coupled with reversed phase high performance liquid chromatography-high resolution mass spectrometry to improve coverage in lipidomics analysis. Anal Chim Acta 954:140–150

    Article  CAS  PubMed  Google Scholar 

  104. 104.

    Mondello L et al (2005) Silver-ion reversed-phase comprehensive two-dimensional liquid chromatography combined with mass spectrometric detection in lipidic food analysis. J Chromatogr A 1086:91–98

    Article  CAS  PubMed  Google Scholar 

  105. 105.

    Dugo P, Kumm T, Crupi ML, Cotroneo A, Mondello L (2006) Comprehensive two-dimensional liquid chromatography combined with mass spectrometric detection in the analyses of triacylglycerols in natural lipidic matrixes. J Chromatogr A 1112:269–275

    Article  CAS  PubMed  Google Scholar 

  106. 106.

    Holčapek M, Ovčačíková M, Lísa M, Cífková E, Hájek T (2015) Continuous comprehensive two-dimensional liquid chromatography–electrospray ionization mass spectrometry of complex lipidomic samples. Anal Bioanal Chem 407:5033–5043

    Article  CAS  PubMed  Google Scholar 

  107. 107.

    Ling YS et al (2014) Two-dimensional LC–MS/MS to enhance ceramide and phosphatidylcholine species profiling in mouse liver. Biomed Chromatogr 28:1284–1293

    Article  CAS  PubMed  Google Scholar 

  108. 108.

    Byrdwell WC (2010) Dual parallel mass spectrometry for lipid and vitamin D analysis. J Chromatogr A 1217:3992–4003

    Article  CAS  PubMed  Google Scholar 

  109. 109.

    Nie H et al (2010) Lipid profiling of rat peritoneal surface layers by online normal- and reversed-phase 2D LC QToF-MS. J Lipid Res 51:2833–2844

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  110. 110.

    Li M et al (2014) A not-stop-flow online normal-/reversed-phase two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry method for comprehensive lipid profiling of human plasma from atherosclerosis patients. J Chromatogr A 1372:110–119

    Article  CAS  Google Scholar 

  111. 111.

    Yang L et al (2017) Lipidomic analysis of plasma in patients with lacunar infarction using normal-phase/reversed-phase two-dimensional liquid chromatography–quadrupole time-of-flight mass spectrometry. Anal Bioanal Chem 409:3211–3222

    Article  CAS  PubMed  Google Scholar 

  112. 112.

    Yang L et al (2015) Comprehensive lipid profiling of plasma in patients with benign breast tumor and breast cancer reveals novel biomarkers. Anal Bioanal Chem 407:5065–5077

    Article  CAS  PubMed  Google Scholar 

  113. 113.

    Bang DY, Moon MH (2013) Online two-dimensional capillary strong anion exchange/reversed phase liquid chromatography–tandem mass spectrometry for comprehensive lipid analysis. J Chromatogr A 1310:82–90

    Article  CAS  PubMed  Google Scholar 

  114. 114.

    Wang S, Zhou L, Wang Z, Shi X, Xu G (2017) Simultaneous metabolomics and lipidomics analysis based on novel heart-cutting two-dimensional liquid chromatography–mass spectrometry. Anal Chim Acta 966:34–40

    Article  CAS  PubMed  Google Scholar 

  115. 115.

    Casetta B, Vecchione G, Tomaiuolo M, Margaglione M, Grandone E (2009) Setting up a 2D-LC/MS/MS method for the rapid quantitation of the prostanoid metabolites 6-oxo-PGF and TXB2 as markers for hemostasis assessment. J Mass Spectrom 44:346–352

    Article  CAS  PubMed  Google Scholar 

  116. 116.

    Jung U, Choi M-S (2014) Obesity and its metabolic complications: the role of adipokines and the relationship between obesity, inflammation, insulin resistance, dyslipidemia and nonalcoholic fatty liver disease. Int J Mol Sci 15:6184–6223

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  117. 117.

    Pietiläinen KH et al (2011) Association of lipidome remodeling in the adipocyte membrane with acquired obesity in humans. PLoS Biol 9:e1000623

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  118. 118.

    Luo L, Liu M (2016) Adipose tissue in control of metabolism. J Endocrinol 231:R77–R99

    Article  CAS  Google Scholar 

  119. 119.

    Kotronen A et al (2010) Comparison of lipid and fatty acid composition of the liver, subcutaneous and intra-abdominal adipose tissue, and serum. Obesity 18:937–944

    Article  CAS  PubMed  Google Scholar 

  120. 120.

    Baker RC, Nikitina Y, Subauste AR (2014) Analysis of adipose tissue lipid using mass spectrometry. Methods Enzymol 538:89–105

    Article  CAS  PubMed  Google Scholar 

  121. 121.

    Sen I et al (2015) Lipid profiles of adipose and muscle tissues in mouse models of juvenile onset of obesity without high fat diet induction: a fourier transform infrared (FT-IR) spectroscopic study. Appl Spectrosc 69:679–688

    Article  CAS  PubMed  Google Scholar 

  122. 122.

    Roberts LD, West JA, Vidal-Puig A, Griffin JL (2014) Methods for performing lipidomics in white adipose tissue. Methods Enzymol 538:211–231

    Article  CAS  PubMed  Google Scholar 

  123. 123.

    Al-Sulaiti H et al (2018) Triglyceride profiling in adipose tissues from obese insulin sensitive, insulin resistant and type 2 diabetes mellitus individuals. J Transl Med 16:175

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  124. 124.

    Guan M et al (2017) Comprehensive qualification and quantification of triacylglycerols with specific fatty acid chain composition in horse adipose tissue, human plasma and liver tissue. Talanta 172:206–214

    Article  CAS  PubMed  Google Scholar 

  125. 125.

    Medina-Gomez G et al (2007) PPAR gamma 2 prevents lipotoxicity by controlling adipose tissue expandability and peripheral lipid metabolism. PLoS Genet 3:e64

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  126. 126.

    Kolak M et al (2007) Adipose tissue inflammation and increased ceramide content characterize subjects with high liver fat content independent of obesity. Diabetes 56:1960–1968

    Article  CAS  PubMed  Google Scholar 

  127. 127.

    Mattila I, Seppänen-Laakso T, Suortti T, Orešič M (2008) Application of lipidomics and metabolomics to the study of adipose tissue. Methods Mol Biol (Clifton NJ) 456:123–130

    Article  Google Scholar 

  128. 128.

    Prieur X et al (2011) Differential lipid partitioning between adipocytes and tissue macrophages modulates macrophage lipotoxicity and M2/M1 polarization in obese mice. Diabetes 60:797–809

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  129. 129.

    Hoene M et al (2014) The lipid profile of brown adipose tissue is sex-specific in mice. Biochim Biophys Acta Mol Cell Biol Lipids 1841:1563–1570

    Article  CAS  Google Scholar 

  130. 130.

    Haensig M et al (2014) Improved mitral valve performance after transapical aortic valve implantation. Ann Thorac Surg 97:1247–1253 (discussion 1253–4)

    Article  PubMed  Google Scholar 

  131. 131.

    Yore MM et al (2014) Discovery of a class of endogenous mammalian lipids with anti-diabetic and anti-inflammatory effects. Cell 159:318–332

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  132. 132.

    Aicheler F et al (2015) Retention time prediction improves identification in nontargeted lipidomics approaches. Anal Chem 87:7698–7704

    Article  CAS  PubMed  Google Scholar 

  133. 133.

    Mcilroy GD et al (2016) Fenretinide mediated retinoic acid receptor signalling and inhibition of ceramide biosynthesis regulates adipogenesis, lipid accumulation, mitochondrial function and nutrient stress signalling in adipocytes and adipose tissue. Biochem Pharmacol 100:86–97

    Article  CAS  PubMed  PubMed Central  Google Scholar 

  134. 134.

    Carroll JB et al (2015) HdhQ111 mice exhibit tissue specific metabolite profiles that include striatal lipid accumulation. PLoS One 10:e0134465

    Article  CAS  PubMed  PubMed Central  Google Scholar 

Download references

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.

Author information

Affiliations

Authors

Corresponding author

Correspondence to Maria Fedorova.

Ethics declarations

Conflict of interest

Authors declare no conflict of interest.

Ethical approval

This article does not contain any studies with human participants or animals performed by any of the authors.

Additional information

Published in Chromatographia’s 50th Anniversary Commemorative Issue.

Electronic supplementary material

Below is the link to the electronic supplementary material.

Supplementary material 1 (XLSX 37 KB)

Rights and permissions

Reprints and Permissions

About this article

Verify currency and authenticity via CrossMark

Cite this article

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

Download citation

Keywords

  • Lipids
  • Lipidomics
  • Liquid chromatography
  • RP-LC
  • NP-LC
  • HILIC
  • Adipose tissue