Analytical and Bioanalytical Chemistry

, Volume 410, Issue 25, pp 6387–6409 | Cite as

Mass spectrometry-based shotgun lipidomics – a critical review from the technical point of view

  • Fong-Fu HsuEmail author


Over the past decade, mass spectrometry (MS)-based “shotgun lipidomics” has emerged as a powerful tool for quantitative and qualitative analysis of the complex lipids in the biological system. The aim of this critical review is to give the interested reader a concise overview of the current state of the technology, focused on lipidomic analysis by mass spectrometry. The pros and cons, and pitfalls associated with each available “shotgun lipidomics” method are discussed; and the new strategies for improving the current methods are described. A list of important papers and reviews that are sufficient rather than comprehensive, covering all the aspects of lipidomics including the workflow, methodology, and fundamentals is also compiled for readers to follow.

Graphical abstract


Lipidomics Mass spectrometry Electrospray ionization MALDI Collision induced dissociation Lipid 





α-hydroxy fatty acyl containing dihydrosphingosine ceramide


α-hydroxy fatty acyl containing ceramide


ω-hydroxy fatty acyl containing ceramide


Collision induced dissociation








Electrospray ionization


Fast atom bombardment


Free fatty acid


Fourier transform ion cyclotron resonance






High resolution


Ion mobility


Liquid chromatography


Matrix assisted laser desorption ionization


Mass spectrometry


Neutral loss scan


Phosphatidic acid










Precursor ion scan


Plasmalogen phosphatidylserine




Supercritical fluid chromatography








Thin layer chromatography




Triple stage quadrupole



This work is supported by US Public Health Service Grants P41-GM103422, P60-DK-20579, P30-DK56341, 4R33HL120760-03 and R01AI130454. The author acknowledges Dr. Cheryl Frankfater and the reviewers for proofreading of the manuscript.

Compliance with ethical standards

Conflict of interest

The author declares no conflict of interest.


  1. 1.
    Fenn JB, Mann M, Meng CK, Wong SF, Whitehouse CM. Electrospray ionization for mass spectrometry of large biomolecules. Science. 1989;246(4926):64–71.CrossRefPubMedGoogle Scholar
  2. 2.
    Whitehouse CM, Dreyer RN, Yamashita M, Fenn JB. Electrospray interface for liquid chromatographs and mass spectrometers. Anal Chem. 1985;57(3):675–9.CrossRefPubMedGoogle Scholar
  3. 3.
    Weintraub ST, Pinckard RN, Hail M. Electrospray ionization for analysis of platelet-activating factor. Rapid Commun Mass Spectrom. 1991;5(7):309–11.CrossRefPubMedGoogle Scholar
  4. 4.
    Kim HY, Wang TC, Ma YC. Liquid chromatography/mass spectrometry of phospholipids using electrospray ionization. Anal Chem. 1994;66(22):3977–82.CrossRefPubMedGoogle Scholar
  5. 5.
    Han X, Gross RW. Structural determination of picomole amounts of phospholipids via electrospray ionization tandem mass spectrometry. J Am Soc Mass Spectrom. 1995;6(12):1202–10.CrossRefPubMedGoogle Scholar
  6. 6.
    Han X, Gross RW. Shotgun lipidomics: electrospray ionization mass spectrometric analysis and quantitation of cellular lipidomes directly from crude extracts of biological samples. Mass Spectrom Rev. 2005;24(3):367–412.CrossRefPubMedGoogle Scholar
  7. 7.
    Han X, Gross RW. Electrospray ionization mass spectroscopic analysis of human erythrocyte plasma membrane phospholipids. Proc Natl Acad Sci USA. 1994;91(22):10635–9.CrossRefPubMedGoogle Scholar
  8. 8.
    Pulfer M, Murphy RC. Electrospray mass spectrometry of phospholipids. Mass Spectrom Rev. 2003;22(5):332–64.CrossRefPubMedGoogle Scholar
  9. 9.
    Hsu F-F, Turk J. Electrospray Ionization with low-energy collisionally activated dissociation tandem mass spectrometry of glycerophospholipids: mechanisms of fragmentation and structural characterization. J Chromatogr B Anal Technol Biomed Life Sci. 2009;877(26):2673–95. Scholar
  10. 10.
    Zemski Berry KA, Hankin JA, Barkley RM, Spraggins JM, Caprioli RM, Murphy RC. MALDI imaging of lipid biochemistry in tissues by mass spectrometry. Chem Rev. 2011;111(10):6491–512. Scholar
  11. 11.
    Murphy RC, Gaskell SJ. New applications of mass spectrometry in lipid analysis. J Biol Chem. 2011;286(29):25427–33. Scholar
  12. 12.
    Brügger B, Erben G, Sandhoff R, Wieland FT, Lehmann WD. Quantitative analysis of biological membrane lipids at the low picomole level by nano-electrospray ionization tandem mass spectrometry. Proc Natl Acad Sci UStA. 1997;94(6):2339–44.CrossRefGoogle Scholar
  13. 13.
    Han X, Gross RW. Global analyses of cellular lipidomes directly from crude extracts of biological samples by ESI mass spectrometry: a bridge to lipidomics. J Lipid Res. 2003;44(6):1071–9.CrossRefPubMedGoogle Scholar
  14. 14.
    Han X, Gross RW. Shotgun lipidomics: multidimensional MS analysis of cellular lipidomes. Expert Rev Proteom. 2005;2(2):253–64.CrossRefGoogle Scholar
  15. 15.
    Welti R, Wang X. Lipid species profiling: a high-throughput approach to identify lipid compositional changes and determine the function of genes involved in lipid metabolism and signaling. Current Opin Plant Biol. 2004;7(3):337–44. Scholar
  16. 16.
    Han X, Jiang X. A review of lipidomic technologies applicable to sphingolipidomics and their relevant applications. Eur J Lipid Sci Technol. 2009;111(1):39–52.CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Yang K, Cheng H, Gross RW, Han X. Automated lipid identification and quantification by multidimensional mass spectrometry-based shotgun lipidomics. Anal Chem. 2009;81(11):4356–68.CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Ståhlman M, Ejsing CS, Tarasov K, Perman J, Borén J, Ekroos K. High throughput shotgun lipidomics by quadrupole time-of-flight mass spectrometry. J Chromatogr B. 2009;877(26):2664–72. Scholar
  19. 19.
    Blanksby SJ, Mitchell TW. Advances in mass spectrometry for lipidomics. Annu Rev Anal Chem. 2010;3:433–65.CrossRefGoogle Scholar
  20. 20.
    Leiker TJ, Barkley RM, Murphy RC. analysis of diacylglycerol molecular species in cellular lipid extracts by normal-phase LC-electrospray mass spectrometry. Int J Mass Spectrom. 2011;305(2/3):103–9.CrossRefPubMedPubMedCentralGoogle Scholar
  21. 21.
    Schwudke D, Schuhmann K, Herzog R, Bornstein SR, Shevchenko A. Shotgun lipidomics on high resolution mass spectrometers. Cold Spring Harb Perspect Biol. 2011;3(9):a004614. Scholar
  22. 22.
    Murphy RC, Leiker TJ, Barkley RM. Glycerolipid and cholesterol ester analyses in biological samples by mass spectrometry. Bioch Biophys Acta. 2011;1811(11):776–83. Scholar
  23. 23.
    Köfeler HC, Fauland A, Rechberger GN, Trötzmüller M. Mass spectrometry based lipidomics: an overview of technological platforms. Metabolites. 2012;2(1):19.CrossRefPubMedPubMedCentralGoogle Scholar
  24. 24.
    Schuhmann K, Almeida R, Baumert M, Herzog R, Bornstein SR, Shevchenko A. Shotgun lipidomics on a LTQ Orbitrap mass spectrometer by successive switching between acquisition polarity modes. J Mass Spectrom. 2012;47(1):96–104. Scholar
  25. 25.
    Han X, Yang K, Gross RW. Multi-dimensional mass spectrometry-based shotgun lipidomics and novel strategies for lipidomic analyses. Mass Spectrom Rev. 2012;31(1):134–78.CrossRefPubMedGoogle Scholar
  26. 26.
    Brügger B. Lipidomics: analysis of the lipid composition of cells and subcellular organelles by electrospray ionization mass spectrometry. Annu Rev Biochem. 2014;83 Scholar
  27. 27.
    Lintonen TP, Baker PR, Suoniemi M, Ubhi BK, Koistinen KM, Duchoslav E, et al. Differential mobility spectrometry-driven shotgun lipidomics. Anal Chem. 2014;86(19):9662–9.CrossRefPubMedGoogle Scholar
  28. 28.
    Papan C, Penkov S, Herzog R, Thiele C, Kurzchalia T, Shevchenko A. Systematic screening for novel lipids by shotgun lipidomics. Anal Chem. 2014;86(5):2703–10. Scholar
  29. 29.
    Roberg-Larsen H, Lund K, Vehus T, Solberg N, Vesterdal C, Misaghian D, et al. Highly automated nano-LC/MS-based approach for thousand cell-scale quantification of side chain-hydroxylated oxysterols. J Lipid Res. 2014;55(7):1531–6. Scholar
  30. 30.
    Lisa M, Holcapek M. High-throughput and comprehensive lipidomic analysis using ultrahigh-performance supercritical fluid chromatography-mass spectrometry. Anal Chem. 2015;87(14):7187–95.CrossRefPubMedGoogle Scholar
  31. 31.
    Paglia G, Kliman M, Claude E, Geromanos S, Astarita G. Applications of ion-mobility mass spectrometry for lipid analysis. Anal Bioanal Chem. 2015;407(17):4995–5007. Scholar
  32. 32.
    Groessl M, Graf S, Knochenmuss R. High resolution ion mobility-mass spectrometry for separation and identification of isomeric lipids. Analyst. 2015;140(20):6904–11. Scholar
  33. 33.
    Surma MA, Herzog R, Vasilj A, Klose C, Christinat N, Morin-Rivron D, et al. An automated shotgun lipidomics platform for high throughput, comprehensive, and quantitative analysis of blood plasma intact lipids. Eur J Lipid Sci Technol. 2015;117(10):1540–9. Scholar
  34. 34.
    Wang C, Wang M, Han X. Applications of mass spectrometry for cellular lipid analysis. Mol Biosyst. 2015;11(3):698–713.CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Almeida R, Pauling JK, Sokol E, Hannibal-Bach HK, Ejsing CS. Comprehensive lipidome analysis by shotgun lipidomics on a hybrid quadrupole-Orbitrap-linear ion trap mass spectrometer. J Am Soc Mass Spectrom. 2015;26(1):133–48. Scholar
  36. 36.
    Ghaste M, Mistrik R, Shulaev V. Applications of Fourier transform ion cyclotron resonance (FT-ICR) and Orbitrap-based high resolution mass spectrometry in metabolomics and lipidomics. Int J Mol Sci. 2016;17(6):816. Scholar
  37. 37.
    Han X. Lipidomics for studying metabolism. Nat Rev Endocrinol. 2016;12(11):668–79.CrossRefGoogle Scholar
  38. 38.
    Ma X, Chong L, Tian R, Shi R, Hu TY, Ouyang Z, et al. Identification and quantitation of lipid C=C location isomers: a shotgun lipidomics approach enabled by photochemical reaction. Proc Natl Acad Sci. 2016;113(10):2573–8. Scholar
  39. 39.
    Wang M, Wang C, Han RH, Han X. Novel advances in shotgun lipidomics for biology and medicine. Prog Lipid Res. 2016;61:83–108.CrossRefPubMedGoogle Scholar
  40. 40.
    Yang K, Han X. Lipidomics: techniques, applications, and outcomes related to biomedical sciences. Trends Biochem Sci. 2016;41(11):954–69.CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Triebl A, Hartler J, Trotzmuller M, Kofeler HC. Lipidomics: prospects from a technological perspective. Biochim Biophys Acta. 2017;22(17):30052–5.Google Scholar
  42. 42.
    Wang C, Wang M, Han X. Comprehensive and quantitative analysis of lysophospholipid molecular species present in obese mouse liver by shotgun lipidomics. Anal Chem. 2015;87(9):4879–87. Scholar
  43. 43.
    Ejsing CS, Sampaio JL, Surendranath V, Duchoslav E, Ekroos K, Klemm RW, et al. Global analysis of the yeast lipidome by quantitative shotgun mass spectrometry. Proc Natl Acad Sci USA. 2009;106(7):2136–41.CrossRefPubMedGoogle Scholar
  44. 44.
    Merrill AH Jr, Sullards MC, Allegood JC, Kelly S, Wang E. Sphingolipidomics: high-throughput, structure-specific, and quantitative analysis of sphingolipids by liquid chromatography tandem mass spectrometry. Methods. 2005;36(2):207–24.CrossRefPubMedGoogle Scholar
  45. 45.
    Yang K, Han X. Accurate quantification of lipid species by electrospray ionization mass spectrometry meets a key challenge in lipidomics. Metabolites. 2011;1(1):21–40. Scholar
  46. 46.
    Laboureur L, Ollero M, Touboul D, Astarita G. Lipidomics by supercritical fluid chromatography. Int J Mol Sci. 2015;16(6):13868–84. Scholar
  47. 47.
    Yamada T, Uchikata T, Sakamoto S, Yokoi Y, Nishiumi S, Yoshida M, et al. Supercritical fluid chromatography/Orbitrap mass spectrometry based lipidomics platform coupled with automated lipid identification software for accurate lipid profiling. J Chromatogr A. 2013;2:237–42.CrossRefGoogle Scholar
  48. 48.
    Taki T. An approach to glycobiology from glycolipidomics: ganglioside molecular scanning in the brains of patients with Alzheimer's disease by TLC-blot/matrix assisted laser desorption/ionization-time of flight MS. Biol Pharm Bull. 2012;35(10):1642–7.CrossRefPubMedGoogle Scholar
  49. 49.
    Schwudke D, Liebisch G, Herzog R, Schmitz G, Shevchenko A. Shotgun lipidomics by tandem mass spectrometry under data-dependent acquisition control. methods in enzymology. 2007;433:175–91. Scholar
  50. 50.
    Ryan E, Reid GE. Chemical derivatization and ultrahigh resolution and accurate mass spectrometry strategies for "shotgun" lipidome analysis. Acc Chem Res. 2016;49(9):1596–604.CrossRefPubMedGoogle Scholar
  51. 51.
    Baker PRS, Armando AM, Campbell JL, Quehenberger O, Dennis EA. Three-dimensional enhanced lipidomics analysis combining UPLC, differential ion mobility spectrometry, and mass spectrometric separation strategies. J Lipid Res. 2014;55(11):2432–42. Scholar
  52. 52.
    Watson AD. Thematic review series: systems biology approaches to metabolic and cardiovascular disorders. lipidomics: a global approach to lipid analysis in biological systems. J Lipid Res. 2006;47(10):2101–11. Scholar
  53. 53.
    Poad BLJ, Zheng X, Mitchell TW, Smith RD, Baker ES, Blanksby SJ. On-line ozonolysis combined with ion mobility-mass spectrometry provides a new platform for lipid isomer analyses. Anal Chem. 2018;90(2):1292–300. Scholar
  54. 54.
    Thomas MC, Mitchell TW, Harman DG, Deeley JM, Nealon JR, Blanksby SJ. Ozone-induced dissociation: elucidation of double bond position within mass-selected lipid ions. Anal Chem. 2008;80(1):303–11. Scholar
  55. 55.
    Fahy E, Subramaniam S, Brown HA, Glass CK, Merrill AH Jr, Murphy RC, et al. A comprehensive classification system for lipids. J Lipid Res. 2005;46(5):839–61.CrossRefPubMedGoogle Scholar
  56. 56.
    Han X, Yang K, Yang J, Fikes KN, Cheng H, Gross RW. Factors influencing the electrospray intrasource separation and selective ionization of glycerophospholipids. J Am Soc Mass Spectrom. 2006;17(2):264–74.CrossRefPubMedGoogle Scholar
  57. 57.
    Hsu FF, Turk J. Electrospray ionization multiple-stage linear ion-trap mass spectrometry for structural elucidation of triacylglycerols: assignment of fatty acyl groups on the glycerol backbone and location of double bonds. J Am Soc Mass Spectrom. 2010;21(4):657–69.CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Hsu FF, Turk J. Structural determination of sphingomyelin by tandem mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom. 2000;11(5):437–49.CrossRefPubMedGoogle Scholar
  59. 59.
    Hsu FF, Turk J. Structural determination of glycosphingolipids as lithiated adducts by electrospray ionization mass spectrometry using low-energy collisional-activated dissociation on a triple stage quadrupole instrument. J Am Soc Mass Spectrom. 2001;12(1):61–79.CrossRefPubMedGoogle Scholar
  60. 60.
    Lin MH, Miner JH, Turk J, Hsu FF. Linear ion-trap MSn with high-resolution MS reveals structural diversity of 1-O-acylceramide family in mouse epidermis. J Lipid Res. 2017;58(4):772–82.CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Han X. Characterization and direct quantitation of ceramide molecular species from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal Biochem. 2002;302(2):199–212.CrossRefPubMedGoogle Scholar
  62. 62.
    Hsu FF, Turk J. Characterization of ceramides by low energy collisional-activated dissociation tandem mass spectrometry with negative-ion electrospray ionization. J Am Soc Mass Spectrom. 2002;13(5):558–70.CrossRefPubMedGoogle Scholar
  63. 63.
    Hsu FF, Turk J (2005) Tandem mass spectrometry with electrospray ionization of sulfatides. In: Caprioli R, Gross ML (Eds.) The Encyclopedia of Mass Spectrometry. Applications in Biochemistry, Biology, and Medicine, vol 3, Part A. Elsevier Science, New York, pp 473–497Google Scholar
  64. 64.
    Hsu FF, Turk J. Studies on sulfatides by quadrupole ion-trap mass spectrometry with electrospray ionization: structural characterization and the fragmentation processes that include an unusual internal galactose residue loss and the classical charge-remote fragmentation. J Am Soc Mass Spectrom. 2004;15(4):536–46.CrossRefPubMedGoogle Scholar
  65. 65.
    Hsu FF, Turk J. Characterization of phosphatidylinositol, phosphatidylinositol-4-phosphate, and phosphatidylinositol-4,5-bisphosphate by electrospray ionization tandem mass spectrometry: a mechanistic study. J Am Soc Mass Spectrom. 2000;11(11):986–99.CrossRefPubMedGoogle Scholar
  66. 66.
    Hsu FF, Turk J, Rhoades ER, Russell DG, Shi Y, Groisman EA. Structural characterization of cardiolipin by tandem quadrupole and multiple-stage quadrupole ion-trap mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom. 2005;16(4):491–504.CrossRefPubMedGoogle Scholar
  67. 67.
    Hsu FF, Turk J (2005) Tandem mass spectrometry with electrospray ionization of sphingomyelins. In: Caprioli R, Gross ML (Eds.) The Encyclopedia of Mass Spectrometry. Applications in Biochemistry, Biology, and Medicine, vol 3, Part A. Elsevier Science, New York, pp 430–447Google Scholar
  68. 68.
    Hsu FF, Turk J, Zhang K, Beverley SM. Characterization of inositol phosphorylceramides from Leishmania major by tandem mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom. 2007;18(9):1591–604.CrossRefPubMedPubMedCentralGoogle Scholar
  69. 69.
    Hsu FF, Turk J. Characterization of phosphatidylethanolamine as a lithiated adduct by triple quadrupole tandem mass spectrometry with electrospray ionization. J Mass Spectrom. 2000;35(5):595–606.CrossRefPubMedGoogle Scholar
  70. 70.
    Kamel AM, Brown PR, Munson B. Effects of Mobile-Phase Additives, Solution pH, Ionization Constant, and Analyte Concentration on the Sensitivities and Electrospray Ionization Mass Spectra of Nucleoside Antiviral Agents. Anal Chem. 1999;71(24):5481–5492. Scholar
  71. 71.
    Schuhmann K, Herzog R, Schwudke D, Metelmann-Strupat W, Bornstein SR, Shevchenko A. Bottom-up shotgun lipidomics by higher energy collisional dissociation on LTQ Orbitrap mass spectrometers. Anal Chem. 2011;83(14):5480–7.CrossRefPubMedGoogle Scholar
  72. 72.
    Liebisch G, Drobnik W, Lieser B, Schmitz G. High-throughput quantification of lysophosphatidylcholine by electrospray ionization tandem mass spectrometry. Clin Chem. 2002;48(12):2217–24.PubMedGoogle Scholar
  73. 73.
    Liebisch G, Binder M, Schifferer R, Langmann T, Schulz B, Schmitz G. High throughput quantification of cholesterol and cholesteryl ester by electrospray ionization tandem mass spectrometry (ESI-MS/MS). Biochim Biophys Acta. 2006;1:121–8.CrossRefGoogle Scholar
  74. 74.
    Liebisch G, Drobnik W, Reil M, Trumbach B, Arnecke R, Olgemoller B, et al. Quantitative measurement of different ceramide species from crude cellular extracts by electrospray ionization tandem mass spectrometry (ESI-MS/MS). J Lipid Res. 1999;40(8):1539–46.Google Scholar
  75. 75.
    Lydic TA, Busik JV, Esselman WJ, Reid GE. Complementary precursor ion and neutral loss scan mode tandem mass spectrometry for the analysis of glycerophosphatidylethanolamine lipids from whole rat retina. Anal Bioanal Chem. 2009;394(1):267–75.CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Hsu FF, Turk J. Charge-remote and charge-driven fragmentation processes in diacyl glycerophosphoethanolamine upon low-energy collisional activation: a mechanistic proposal. J Am Soc Mass Spectrom. 2000;11(10):892–9.CrossRefPubMedGoogle Scholar
  77. 77.
    Han X, Yang K, Cheng H, Fikes KN, Gross RW. Shotgun lipidomics of phosphoethanolamine-containing lipids in biological samples after one-step in situ derivatization. J Lipid Res. 2005;46(7):1548–60. Scholar
  78. 78.
    Hsu F-F, Turk J, Stewart ME, Downing DT. Structural studies on ceramides as lithiated adducts by low energy collisional-activated dissociation tandem mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom. 2002;13(6):680–95. Scholar
  79. 79.
    Gu M, Kerwin JL, Watts JD, Aebersold R. Ceramide profiling of complex lipid mixtures by electrospray ionization mass spectrometry. Anal Biochem. 1997;244(2):347–56. Scholar
  80. 80.
    Wang M, Wang C, Han X. Selection of internal standards for accurate quantification of complex lipid species in biological extracts by electrospray ionization mass spectrometry – what, how and why? Mass Spectrom Rev. 2017;36(6):693–714. Scholar
  81. 81.
    Hsu FF, Kuhlmann FM, Turk J, Beverley SM. Multiple-stage linear ion-trap with high resolution mass spectrometry towards complete structural characterization of phosphatidylethanolamines containing cyclopropane fatty acyl chain in Leishmania infantum. J Mass Spectrom. 2014;49(3):201–9.CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Hsu FF, Turk J. Studies on phosphatidylserine by tandem quadrupole and multiple stage quadrupole ion-trap mass spectrometry with electrospray ionization: structural characterization, and the fragmentation processes. J Am Soc Mass Spectrom. 2005;16(9):1510–22.CrossRefPubMedGoogle Scholar
  83. 83.
    Hsu F-F, Bohrer A, Turk J. Formation of lithiated adducts of glycerophosphocholine lipids facilitates their identification by electrospray ionization tandem mass spectrometry. J Am Soc Mass Spectrom. 1998;9(5):516–26. Scholar
  84. 84.
    Yang K, Zhao Z, Gross RW, Han X. Systematic analysis of choline-containing phospholipids using multi-dimensional mass spectrometry-based shotgun lipidomics. J Chromatogr B Analyt Technol Biomed Life Sci. 2009;877(26):2924–36.CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Yost RA, Enke CG. Triple quadrupole mass spectrometry for direct mixture analysis and structure elucidation. Anal Chem. 1979;51(12):1251–64.CrossRefPubMedGoogle Scholar
  86. 86.
    Singleton KE, Cooks RG, Wood KV. Utilization of natural isotopic abundance ratios in tandem mass spectrometry. AnalChem. 1983;55(4):762–4. Scholar
  87. 87.
    Snyder DT, Cooks RG. Single analyzer neutral loss scans in a linear quadrupole ion trap using orthogonal double resonance excitation. Anal Chem. 2017;89(15):8148–55. Scholar
  88. 88.
    Song H, Hsu FF, Ladenson J, Turk J. Algorithm for processing raw mass spectrometric data to identify and quantitate complex lipid molecular species in mixtures by data-dependent scanning and fragment ion database searching. J Am Soc Mass Spectrom. 2007;18(10):1848–58.CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Han X, Gross RW. Quantitative analysis and molecular species fingerprinting of triacylglyceride molecular species directly from lipid extracts of biological samples by electrospray ionization tandem mass spectrometry. Anal Biochem. 2001;295(1):88–100.CrossRefPubMedGoogle Scholar
  90. 90.
    Hsu FF, Turk J. Structural characterization of triacylglycerols as lithiated adducts by electrospray ionization mass spectrometry using low-energy collisionally activated dissociation on a triple stage quadrupole instrument. J Am Soc Mass Spectrom. 1999;10(7):587–99.CrossRefPubMedGoogle Scholar
  91. 91.
    Murphy RC, James PF, McAnoy AM, Krank J, Duchoslav E, Barkley RM. Detection of the abundance of diacylglycerol and triacylglycerol molecular species in cells using neutral loss mass spectrometry. Anal Biochem. 2007;366(1):59–70. Scholar
  92. 92.
    Li M, Baughman E, Roth MR, Han X, Welti R, Wang X. Quantitative profiling and pattern analysis of triacylglycerol species in Arabidopsis seeds by electrospray ionization mass spectrometry. Plant J. 2014;77(1):160–72.CrossRefPubMedGoogle Scholar
  93. 93.
    Li M, Butka E, Wang X (2014) Comprehensive quantification of triacylglycerols in soybean seeds by electrospray ionization mass spectrometry with multiple neutral loss scans. Sci Rep 4 (6581).Google Scholar
  94. 94.
    Andrikopoulos NK. Chromatographic and spectroscopic methods in the analysis of triacylglycerol species and regiospecific isomers of oils and fats. Critical Revi Food Sci Nutr. 2002;42(5):473–505. Scholar
  95. 95.
  96. 96.
    Schuhmann K, Thomas H, Ackerman JM, Nagornov KO, Tsybin YO, Shevchenko A (2017) Intensity-independent noise filtering in FT MS and FT MS/MS spectra for shotgun lipidomics. Anal Chem 1 (10).Google Scholar
  97. 97.
    Markarov A, Cousijn E, Cantebury J, Denisov E, Thoeing C, Lange O, Kreutzman A, Ayzikov K, Damoc E, Tabiwang A, Xuan Y, Sharma S, Huguet R, McAlister G, Senko M, Zabrouskov V, Harder A. Extension of Orbitrap capabilities to enable new applications. In: 65th Conference on Mass Spectrometry and Allied Topics, Indianapolis, IN, June 4 2017.Google Scholar
  98. 98.
    Wang M, Huang Y, Han X. Accurate mass searching of individual lipid species candidates from high-resolution mass spectra for shotgun lipidomics. Rapid Commun Mass Spectrom. 2014;28(20):2201–10. Scholar
  99. 99.
    Bielow C, Mastrobuoni G, Orioli M, Kempa S. On mass ambiguities in high-resolution shotgun lipidomics. Anal Chem. 2017;89(5):2986–94.CrossRefPubMedGoogle Scholar
  100. 100.
    Hsu F-F, Lodhi IJ, Turk J, Semenkovich CF. Structural distinction of diacyl-, alkylacyl, and Alk-1-enylacyl glycerophosphocholines as [M – 15]– ions by multiple-stage linear ion-trap mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom. 2014;25(8):1412–20. Scholar
  101. 101.
    Snyder DT, Szalwinski LJ, Cooks RG. Simultaneous and sequential MS/MS scan combinations and permutations in a linear quadrupole ion trap. Analy Chem. 2017;89(20):11053–60. Scholar
  102. 102.
    Fuchs B, Suss R, Schiller J. An update of MALDI-TOF mass spectrometry in lipid research. Prog Lipid Res. 2010;49(4):450–75.CrossRefGoogle Scholar
  103. 103.
    Schiller J, Suss R, Arnhold J, Fuchs B, Lessig J, Muller M, et al. Matrix-assisted laser desorption and ionization time-of-flight (MALDI-TOF) mass spectrometry in lipid and phospholipid research. Prog Lipid Res. 2004;43(5):449–88.CrossRefPubMedGoogle Scholar
  104. 104.
    Schiller J, Arnhold J, Benard S, Müller M, Reichl S, Arnold K. Lipid analysis by matrix-assisted laser desorption and ionization mass spectrometry: a methodological approach. Anal Biochem. 1999;267(1):46–56. Scholar
  105. 105.
    Li YL, Gross ML, Hsu FF. Ionic-liquid matrices for improved analysis of phospholipids by MALDI-TOF mass spectrometry. J Am Soc Mass Spectrom. 2005;16(5):679–82.CrossRefPubMedGoogle Scholar
  106. 106.
    Jackson SN, Ugarov M, Egan T, Post JD, Langlais D, Schultz JA, et al. MALDI-ion mobility-TOFMS imaging of lipids in rat brain tissue. J Mass Spectrometry: JMS. 2007;42(8):1093–8. Scholar
  107. 107.
    Rujoi M, Estrada R, Yappert MC. In situ MALDI-TOF MS regional analysis of neutral phospholipids in lens tissue. Anal Chem. 2004;76(6):1657–63.CrossRefPubMedGoogle Scholar
  108. 108.
    McDonnell LA, Heeren RM. Imaging mass spectrometry. Mass Spectrom Rev. 2007;26(4):606–43.CrossRefPubMedGoogle Scholar
  109. 109.
    Wu Q, Chu JL, Rubakhin SS, Gillette MU, Sweedler JV. Dopamine-modified TiO(2) monolith-assisted LDI MS imaging for simultaneous localization of small metabolites and lipids in mouse brain tissue with enhanced detection selectivity and sensitivity (Electronic supplementary information (ESI) available) see DOI: 10.1039/c7sc00937b for additional data file. Chem Sci. 2017;8(5):3926–38. Scholar
  110. 110.
    Petkovic M, Schiller J, Muller M, Benard S, Reichl S, Arnold K, et al. Detection of individual phospholipids in lipid mixtures by matrix-assisted laser desorption/ionization time-of-flight mass spectrometry: phosphatidylcholine prevents the detection of further species. Anal Biochem. 2001;289(2):202–16.CrossRefPubMedGoogle Scholar
  111. 111.
    Zhou P, Altman E, Perry MB, Li J. Study of matrix additives for sensitive analysis of lipid a by matrix-assisted laser desorption ionization mass spectrometry. Appl Environ Microbiol. 2010;76(11):3437–43. Scholar
  112. 112.
    Hsu F-F, Turk J, Owens RM, Rhoades ER, Russell DG. Structural characterization of phosphatidyl-myo-inositol mannosides from mycobacterium bovis Bacillus calmette guérin by multiple-stage quadrupole ion-trap mass spectrometry with electrospray ionization. I. PIMs and Lyso-PIMs. J Am Soc Mass Spectrom. 2007;18(3):466–78. Scholar
  113. 113.
    Soltwisch J, Kettling H, Vens-Cappell S, Wiegelmann M, Müthing J, Dreisewerd K. Mass spectrometry imaging with laser-induced postionization. Science. 2015;348(6231):211–5. Scholar
  114. 114.
    Ellis SR, Soltwisch J, Paine MRL, Dreisewerd K, Heeren RMA. Laser post-ionization combined with a high resolving power orbitrap mass spectrometer for enhanced MALDI-MS imaging of lipids. Chem Commun. 2017;53(53):7246–9. Scholar
  115. 115.
    Pittenauer E, Allmaier G. The renaissance of high-energy CID for structural elucidation of complex lipids: MALDI-TOF/RTOF-MS of alkali cationized triacylglycerols. J Am Soc Mass Spectrom. 2009;20(6):1037–47. Scholar
  116. 116.
    Pittenauer E, Rehulka P, Winkler W, Allmaier G. Collision-induced dissociation of aminophospholipids (PE, MMPE, DMPE, PS): an apparently known fragmentation process revisited. Anal Bioanal Chem. 2015;407(17):5079–89.CrossRefPubMedGoogle Scholar
  117. 117.
    Trimpin S, Clemmer DE, McEwen CN. Charge-remote fragmentation of lithiated fatty acids on a TOF-TOF instrument using matrix-ionization. J Am Soc Mass Spectrom. 2007;18(11):1967–72. Scholar
  118. 118.
    Spengler B. Post-source decay analysis in matrix-assisted laser desorption/ionization mass spectrometry of biomolecules. J Mass Spectrom. 1997;32:1019–36.CrossRefGoogle Scholar
  119. 119.
    Cotter RJ, Gardner BD, Iltchenko S, English RD. Tandem time-of-flight mass spectrometry with a curved field reflectron. Anal Chem. 2004;76(7):1976–81.CrossRefPubMedGoogle Scholar
  120. 120.
    Cornish TJ, Cotter RJ. A curved-field reflectron for improved energy focusing of product ions in time-of-flight mass spectrometry. Rapid Commun Mass Spectrom. 1993;7(11):1037–40.CrossRefPubMedGoogle Scholar
  121. 121.
    Belgacem O, Pittenauer E, Openshaw ME, Hart PJ, Bowdler A, Allmaier G. Axial spatial distribution focusing: improving MALDI-TOF/RTOF mass spectrometric performance for high-energy collision-induced dissociation of biomolecules. Rapid Commun Mass Spectrom. 2016;30(3):343–51. Scholar
  122. 122.
    Suckau D, Resemann A, Schuerenberg M, Hufnagel P, Franzen J, Holle A. A novel MALDI LIFT-TOF/TOF mass spectrometer for proteomics. Anal Bioanal Chem. 2003;376(7):952–65. Scholar
  123. 123.
    Frankfater C, Jiang X, Hsu FF (2018) Characterization of long-chain fatty acid as N-(4-aminomethylphenyl) pyridinium derivative by MALDI LIFT-TOF/TOF mass spectrometry J Am Soc Mass Spectrom. 2018: 29(8) 1688–99.CrossRefPubMedGoogle Scholar
  124. 124.
    Satoh T, Sato T, Kubo A, Tamura J. Tandem time-of-flight mass spectrometer with high precursor ion selectivity employing spiral ion trajectory and improved offset parabolic reflectron. J Am Soc Mass Spectrom. 2011;22(5):797–803.CrossRefPubMedGoogle Scholar
  125. 125.
    Yan Y, Ubukata M, Cody RB, Holy TE, Gross ML. High-energy collision-induced dissociation by MALDI TOF/TOF causes charge-remote fragmentation of steroid sulfates. J Am Soc Mass Spectrom. 2014;25(8):1404–11. Scholar
  126. 126.
    Shimma S, Kubo A, Satoh T, Toyoda M. Detailed structural analysis of lipids directly on tissue specimens using a MALDI-SpiralTOF-Reflectron TOF mass spectrometer. PLoS ONE. 2012;7(5):e37107. Scholar
  127. 127.
    Peršurić Ž, Osuga J, Galinac Grbac T, Peter-Katalinić J, Kraljević Pavelić S. MALDI-SpiralTOF technology for assessment of triacylglycerols in Croatian olive oils. Eur J Lipid Sci Technol. 2016; Scholar
  128. 128.
    Kubo A, Satoh T, Itoh Y, Hashimoto M, Tamura J, Cody RB. Structural analysis of triacylglycerols by using a MALDI-TOF/TOF system with monoisotopic precursor selection. J Am Soc Mass Spectrom. 2013;24(5):684–9. Scholar
  129. 129.
    Lydic TA, Goo Y-H. Lipidomics unveils the complexity of the lipidome in metabolic diseases. Clin Translational Med. 2018;7:4. Scholar
  130. 130.
    Abbassi-Ghadi N, Jones EA, Gomez-Romero M, Golf O, Kumar S, Huang J, et al. A comparison of DESI-MS and LC-MS for the lipidomic profiling of human cancer tissue. J Am Soc Mass Spectrom. 2016;27(2):255–64.CrossRefPubMedGoogle Scholar
  131. 131.
    Strittmatter N, Lovrics A, Sessler J, McKenzie JS, Bodai Z, Doria ML, et al. Shotgun lipidomic profiling of the NCI60 cell line panel using rapid evaporative ionization mass spectrometry. Anal Chem. 2016;88(15):7507–14. Scholar
  132. 132.
    Li L-H, Hsieh H-Y, Hsu C-C. Clinical application of ambient ionization mass spectrometry. Mass Spectrom. 2017;6(Special Issue):S0060. Scholar
  133. 133.
    Luptakova D, Pluhacek T, Palyzova A, Prichystal J, Balog J, Lemr K, et al. Meet interesting abbreviations in clinical mass spectrometry: from compound classification by REIMS to multimodal and mass spectrometry imaging (MSI). Acta Virol. 2017;61(3):353–60.CrossRefPubMedGoogle Scholar
  134. 134.
    Takats Z, Strittmatter N, McKenzie JS. Ambient mass spectrometry in cancer research. Adv Cancer Res. 2017;134:231–56.CrossRefPubMedGoogle Scholar
  135. 135.
    Zhang X, Reid GE. Multistage tandem mass spectrometry of anionic phosphatidylcholine lipid adducts reveals novel dissociation pathways. Int J Mass Spectrom. 2006;252(3):242–55. Scholar
  136. 136.
    Hsu F-F. Complete structural characterization of ceramides as [M – H](−) ions by multiple-stage linear ion trap mass spectrometry. Biochimie. 2016;130:63–75. Scholar
  137. 137.
    Tatituri RV, Wolf BJ, Brenner MB, Turk J, Hsu FF. Characterization of polar lipids of Listeria monocytogenes by HCD and low-energy CAD linear ion-trap mass spectrometry with electrospray ionization. Anal Bioanal Chem. 2015;407(9):2519–28.CrossRefPubMedPubMedCentralGoogle Scholar
  138. 138.
    Baba T, Campbell JL, Le Blanc JCY, Baker PRS. Distinguishing Cis and Trans isomers in intact complex lipids using electron impact excitation of ions from organics mass spectrometry. Anal Chem. 2017;89(14):7307–15.CrossRefPubMedGoogle Scholar
  139. 139.
    Poad BL, Pham HT, Thomas MC, Nealon JR, Campbell JL, Mitchell TW, et al. Ozone-induced dissociation on a modified tandem linear ion-trap: observations of different reactivity for isomeric lipids. J Am Soc Mass Spectrom. 2010;21(12):1989–99.CrossRefPubMedGoogle Scholar
  140. 140.
    Hsu FF, Turk J. Structural characterization of unsaturated glycerophospholipids by multiple-stage linear ion-trap mass spectrometry with electrospray ionization. J Am Soc Mass Spectrom. 2008;19(11):1681–91.CrossRefPubMedPubMedCentralGoogle Scholar
  141. 141.
    Yang K, Dilthey BG, Gross RW. Identification and quantitation of fatty acid double bond positional isomers: a shotgun lipidomics approach using charge-switch derivatization. Anal Chem. 2013;85(20):9742–50. Scholar
  142. 142.
    Wang M, Han RH, Han X. Fatty acidomics: global analysis of lipid species containing a carboxyl group with a charge-remote fragmentation-assisted approach. Anal Chem. 2013;85(19):9312–20. Scholar
  143. 143.
    Bollinger JG, Thompson W, Lai Y, Oslund RC, Hallstrand TS, Sadilek M, et al. Improved sensitivity mass spectrometric detection of eicosanoids by charge reversal derivatization. Anal Chem. 2010;82(16):6790–6. Scholar
  144. 144.
    Hsu F-F, Bohrer A, Wohltmann M, Ramanadham S, Ma Z, Yarasheski K, et al. Electrospray ionization mass spectrometric analyses of changes in tissue phospholipid molecular species during the evolution of hyperlipidemia and hyperglycemia in Zucker diabetic fatty rats. Lipids. 2000;35(8):839–52. Scholar
  145. 145.
    Koivusalo M, Haimi P, Heikinheimo L, Kostiainen R, Somerharju P. Quantitative determination of phospholipid compositions by ESI-MS: effects of acyl chain length, unsaturation, and lipid concentration on instrument response. J Lipid Res. 2001;42(4):663–72.PubMedGoogle Scholar
  146. 146.
    Sampaio JL, Gerl MJ, Klose C, Ejsing CS, Beug H, Simons K, et al. Membrane lipidome of an epithelial cell line. Proc Natl Acad Sci. 2011;108(5):1903–7. Scholar
  147. 147.
    Kalvodova L, Sampaio JL, Cordo S, Ejsing CS, Shevchenko A, Simons K. The lipidomes of Vesicular Stomatitis virus, Semliki Forest virus, and the host plasma membrane analyzed by quantitative shotgun mass spectrometry. J Virol. 2009;83(16):7996–8003. Scholar
  148. 148.
    Bilgin M, Nylandsted J, Jäättelä M, Maeda K (2017) Quantitative profiling of lysosomal lipidome by shotgun lipidomics. Methods Mol Biol 1594, doi: Scholar
  149. 149.
    Rolim AEH, Henrique-Araújo R, Ferraz EG, de Araújo Alves Dultra FK, Fernandez LG. Lipidomics in the study of lipid metabolism: current perspectives in the omic sciences. Gene. 2015;554(2):131–9. Scholar
  150. 150.
    Forrester JS, Milne SB, Ivanova PT, Brown HA. Computational lipidomics: a multiplexed analysis of dynamic changes in membrane lipid composition during signal transduction. Mol Pharmacol. 2004;65(4):813–21.CrossRefPubMedGoogle Scholar
  151. 151.
    Milne S, Ivanova P, Forrester J, Alex Brown H. Lipidomics: an analysis of cellular lipids by ESI-MS. Methods. 2006;39(2):92–103.CrossRefPubMedGoogle Scholar
  152. 152.
    Gross RW, Han X. Shotgun lipidomics of neutral lipids as an enabling technology for elucidation of lipid-related diseases. Am J Physiol Endocrinol Metab. 2009;297(2):6.CrossRefGoogle Scholar
  153. 153.
    Wenk MR. Lipidomics: new tools and applications. Cell. 2010;143(6):888–95. Scholar
  154. 154.
    Wenk MR. The emerging field of lipidomics. Nat Rev Drug Discov. 2005;4(7):594–610.CrossRefPubMedGoogle Scholar
  155. 155.
    Taguchi R, Ishikawa M. Precise and global identification of phospholipid molecular species by an Orbitrap mass spectrometer and automated search engine LipidSearch. J Chromatogr A. 2010;18(25):4229–39.CrossRefGoogle Scholar
  156. 156.
    Herzog R, Schuhmann K, Schwudke D, Sampaio JL, Bornstein SR, Schroeder M, et al. LipidXplorer: a software for consensual cross-platform lipidomics. PLOS ONE. 2012;7(1):17.CrossRefGoogle Scholar
  157. 157.
    Husen P, Tarasov K, Katafiasz M, Sokol E, Vogt J, Baumgart J, Nitsch R, Ekroos K, Ejsing CS (2013) Analysis of lipid experiments (ALEX): a software framework for analysis of high-resolution shotgun lipidomics data. PLOS ONE 8 (11).CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Kind T, Liu KH, Lee DY, DeFelice B, Meissen JK, Fiehn O. LipidBlast in silico tandem mass spectrometry database for lipid identification. Nat Methods. 2013;10(8):755–8.CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Mass Spectrometry Resource, Division of Endocrinology, Diabetes, Metabolism, and Lipid Research, Department of Internal MedicineWashington University School of MedicineSt. LouisUSA

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