Mass Spectrometry for Lipidomics: Methods and Applications. 2-Volume Set

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Mass Spectrometry for Lipidomics All-in-one guide to successful lipidomic analysis, combining the latest advances and best practices from academia, industry, and clinical research Mass Spectrometry for Lipidomics presents a systematic overview of lipidomic analysis, covering established standards of lipid analysis, available technology, and key lipid classes, as well as applications in basic research, medicine, pharma, and the food industry. Through connecting recent technological advances with key application areas, this unique guide bridges the gap between academia and industry by translating the vast body of knowledge that has been gained in the past decade into much-needed practical advice for novices as well as routine users. Edited by the president and vice-president of the International Lipidomics Society with contributions from the top experts in lipid analysis, Mass Spectrometry for Lipidomics covers a wide range of key topics, including: Aspects of sample preparation, separation methods, different mass spectrometry modes, as well as identification and quantitation, including the use of bioinformatics tools for data analysis Identification, quantitation and profiling of lipids in different types of biological samples Analytical approaches for all major classes of biological lipids, from fatty acids to phospholipids to sterols Novel applications in biological research, clinical diagnostics, as well as food and crop science For analytical chemists, biochemists, clinical chemists, and analytical laboratories and hospitals, Mass Spectrometry for Lipidomics presents a comprehensive and authoritative overview of the subject, with unmatched expertise from practicing professionals actively involved in the latest research. Cover Volume 1 Half Title Mass Spectrometry for Lipidomic: Methods and Applications. Volume 1 Copyright Contents Preface 1. Introduction to Lipidomics 1.1 Preface 1.2 Historical Perspective 1.3 Sampling and Preanalytics 1.4 Reference Materials and Biological Reference Ranges 1.5 Clinical Lipidomics 1.6 Identification and Annotation 1.7 Quantitation 1.8 Lipid Ontology References Part I: Analytical Methodologies in Lipidomics 2. Preanalytics for Lipidomics Analysis 2.1 Safety 2.2 Introduction 2.3 Sample Origin 2.4 Sample Collection 2.5 Tissue Homogenization 2.5.1 Mortar and Pestle 2.5.2 Rotor–Stator 2.5.3 Blender 2.5.4 Potter-Elvehjem 2.5.5 Bead Mill 2.6 Liquid–Liquid Extraction (LLE) 2.6.1 Folch Method 2.6.2 Bligh and Dyer (BD) Method 2.6.3 Modified Folch and Bligh/Dyer (BD) Methods 2.6.4 Rose and Oaklander (RO) Method 2.6.5 Matyash or Methyl-tert-Butyl Ether (MTBE) Method 2.6.6 BUME Method 2.6.7 Alshehry Method 2.6.8 Three-Phase Lipid Extraction (3PLE) 2.7 Resuspension and Solubilization 2.8 Automation 2.9 Tips and Tricks Acknowledgments References 3. Direct Infusion (Shotgun) Electrospray Mass Spectrometry 3.1 Introduction 3.2 Complexity of Crude Lipid Extracts 3.2.1 Main Lipid Classes in Mammalian Samples 3.2.2 Bond Types as Structural Features 3.2.3 Fatty Acids as the Major Building Blocks 3.2.4 Lipid Species and Double-Bond Series 3.3 Introduction to Mass Spectrometry of Lipids 3.3.1 Annotation of Lipid Structures Analyzed by MS 3.3.2 Isomers 3.3.3 Isobars and the Type-II Isotopic Overlap 3.4 Overview of Direct Infusion MS Workflows 3.5 Sample Preparation 3.5.1 Preanalytics – Sample Stability 3.5.2 Lipid Extraction 3.5.3 Solvents, Additives, and Lipid Concentration 3.5.4 Sample Derivatization 3.6 Direct Infusion 3.7 Mass Spectrometry Analysis 3.7.1 Electrospray Ionization of Lipids 3.7.2 Tandem Mass Spectrometry 3.7.3 Multidimensional MS Shotgun Lipidomics 3.7.4 High-Resolution Mass Spectrometry 3.8 Lipid Identification 3.8.1 Identification by MS/MS 3.8.2 Identification by HRMS 3.8.3 Consideration of Type-II Overlap 3.8.4 Identification Hierarchy 3.8.5 Caveats/Pitfalls 3.9 Lipid Quantification 3.9.1 Internal Standards 3.9.2 Type-I Isotopic Effect 3.9.3 Evaluation and Correction of Isotopic Overlap 3.9.4 Species Response 3.9.5 Calculation of Concentration 3.10 Data Analysis/Software 3.11 Limitations 3.12 Selected Applications 3.12.1 Analysis of Plasma 3.12.2 Analysis of Tissues and Cells 3.12.3 Analysis of Lipid Metabolism 3.13 Outlook References 4. Liquid Chromatography – and Supercritical Fluid Chromatography – Mass Spectrometry 4.1 Introduction 4.2 Lipid Class Separation 4.2.1 Normal-Phase Liquid Chromatography 4.2.2 Hydrophilic Interaction Liquid Chromatography 4.2.3 Supercritical Fluid Chromatography 4.3 Lipid Species Separation 4.3.1 Reversed-Phase Liquid Chromatography 4.3.2 Nonaqueous Reversed-Phase Liquid Chromatography 4.4 Other Separation Approaches 4.4.1 Silver Ion Chromatography 4.4.2 Chiral Chromatography 4.4.3 Multidimensional Approaches References 5. Mass Spectrometry Imaging of Lipids 5.1 Introduction 5.2 SamplePreparation for Mass Spectrometry Imaging of Lipids 5.2.1 Tissue Samples 5.2.2 Sectioning and Mounting 5.2.3 Cell Culture 5.2.4 Pre-processing 5.2.5 Handling and Storage 5.2.6 Formalin-Fixed Paraffin-Embedded Tissue 5.3 Desorption/Ionization Techniques used for MSI of Lipids 5.3.1 Matrix-Assisted Laser Desorption/Ionization (MALDI) 5.3.2 Secondary Ion Mass Spectrometry SIMS 5.3.3 MSI Methods Using Electrospray Ionization 5.3.3.1 Desorption Electrospray Ionization 5.3.3.2 Laser Ablation Electrospray Ionization and IR-Matrix-Assisted Laser Desorption-Electrospray Ionization 5.3.3.3 Nanospray Desorption Electrospray Ionization 5.4 CombiningIon Mobility of Lipids with MSI 5.5 OnTissue Chemical Derivatization for MSI 5.6 Quantificationin MSI 5.7 LipidIdentification for MSI 5.7.1 Types of Ions Generated by MSI 5.7.2 In-source Fragmentation Considerations 5.7.3 MSI Lipid Identification Using Accurate Mass 5.7.4 Deploying MS/MS for Lipid Identification in MSI 5.7.5 Isomer-Resolved MSI 5.8 Conclusions References 6. Ion Mobility Spectrometry 6.1 Ion Mobility Spectrometry 6.1.1 Introduction 6.1.2 Ion Mobility Spectrometry Techniques and Platforms 6.1.2.1 Drift Tube Ion Mobility Spectrometry (DTIMS) 6.1.2.2 Traveling-WaveIon Mobility Spectrometry (TWIMS) 6.1.2.3 Trapped Ion Mobility Spectrometry (TIMS) 6.1.2.4 Field Asymmetric Ion Mobility Spectrometry (FAIMS) 6.1.3 Ion Mobility Resolving Power (Rp) Advancements 6.1.3.1 Cyclic IMS (cIM) 6.1.3.2 Standard Lossless Ion Manipulation (SLIM) 6.1.3.3 Tandem IMS 6.1.3.4 IMS Data Deconvolution Software Strategies 6.1.3.5 Drift Gas Dopants and Modifiers 6.1.4 Benefits of IMS for Lipidomics 6.1.4.1 Chemical Space Separation with IMS 6.1.4.2 Lipid Identification and Characterization with CCS 6.1.4.3 CCS for Lipid Structural Analysis 6.1.5 Lipidomic Applications with IMS 6.1.5.1 IMS in Imaging and Shotgun Lipidomics 6.1.5.2 IMS-MS/MS and Novel Speciation Approaches 6.1.6 Conclusions and Outlook of IMS for Lipidomics References 7. Structural Characterization of Lipids Using Advanced Mass Spectrometry Approaches 7.1 Introduction 7.2 Structure and Position of Aliphatic Chains in Lipids 7.2.1 Double and Triple Bonds 7.2.1.1 Charge-Switch Derivatization of Fatty Acids 7.2.1.2 Ozone-Induced Dissociation 7.2.1.3 Paternò–Büchi Reaction 7.2.1.4 Epoxidation of Double Bonds 7.2.1.5 Acetonitrile-Related Adducts in APCI 7.2.1.6 Photodissociation of Unsaturated Lipids 7.2.1.7 Electron-Induced Dissociation of Unsaturated Lipids 7.2.2 Methyl Branching of Aliphatic Chains 7.2.3 Oxygen-Containing Functional Groups and Carbocyclic Structures 7.2.4 Stereospecific Position of Acyl Chain on Glycerol 7.3 Conclusions and Outlook References 8. Lipidomic Identification 8.1 Overview 8.2 Chromatography 8.3 Mass Spectrometry 8.3.1 Exact Mass 8.3.2 Fragment Spectra 8.3.2.1 General Considerations 8.3.2.2 Fatty Acids 8.3.2.3 Oxylipins 8.3.2.4 Phospholipids 8.3.2.5 Sphingolipids 8.3.2.6 Glycerolipids 8.3.2.7 Sterols 8.3.3 Deep Structure Determination 8.4 Ion Mobility Spectrometry 8.5 Identification Workflows References 9. Lipidomics Quantitation 9.1 Introduction to Lipidomics Quantitation 9.2 Principle of Quantitation 9.3 Internal Standards 9.4 Isotopic Correction 9.4.1 Isotopic Correction Type I 9.4.2 Isotopic Correction Type II 9.5 Common Approaches for Lipidomics Quantitation 9.5.1 Shotgun MS 9.5.2 Chromatography – MS 9.6 Validation 9.7 Quality Control (QC) References 10. The Past and Future of Lipidomics Bioinformatics 10.1 Introduction 10.2 A Modular Lipidomics Workflow 10.2.1 Data Formats 10.3 Targeted Lipidomics: Assay Design and Raw Data Analysis with LipidCreator and Skyline 10.4 Untargeted Lipidomics: Assay Design and Raw Data Analysis with LipidXplorer 10.5 Standardization of Lipidomics Data with Goslin and lxPostman 10.6 Visualization and Lipidome Comparison with LUX Score and Beyond 10.7 Storage in Lipid Databases: What Is Currently There and What Should Be There 10.8 Outlook 10.8.1 Compatible Interfaces Between Modules 10.8.2 Quality Control 10.8.3 Reusability References Index Volume 2 Half Title Mass Spectrometry for Lipidomic: Methods and Applications. Volume 2 Copyright Copyright Page Contents Preface Part II: Lipidomic Analysis According to Lipid Categories and Classes 11. Fatty Acids: Structural and Quantitative Analysis 11.1 Fatty Acids/Acyl Groups as Analytical Targets 11.1.1 Fatty Acid Classification 11.1.2 Conventional Gas Chromatography (GC)–Mass Spectrometry (MS) 11.1.2.1 High-Resolution GC 11.1.2.2 DMOX (4,4-Dimethyloxazoline) Derivatization 11.1.2.3 Picolinyl Ester (3-Pyridylcarbinol) 11.1.3 GC-Solvent-Mediated (SM) Covalent Adduct Chemical Ionization (CACI)-MS/MS 11.1.3.1 Assignment of Double-Bond Position 11.1.3.2 Geometry of Double Bonds in Conjugated Linoleic Acids 11.1.3.3 Identification of Branched-Chain FA (BCFA) 11.1.3.4 Quantitative Analysis by SM Chemical Ionization and SM-CACI-MS/MS 11.1.4 Electrospray Ionization (ESI) Methods 11.1.4.1 Conventional ESI 11.1.4.2 Ozone-Induced Dissociation (OzID) 11.1.4.3 Paternò–Büchi (PB) Reaction 11.1.4.4 Ion–Ion Chemistry 11.1.4.5 Epoxidation 11.1.4.6 Silver Ion Liquid Chromatography-ESI 11.1.5 Characterization of Deuteration in Fatty Acids 11.1.6 Conclusion References 12. Quantitation of Oxylipins in Biological Samples, Focusing on Plasma, and Urine 12.1 Introduction 12.2 Analysis of Oxylipins: Plasma, Tissues, and Cells 12.2.1 Planning of Sample Collection Preparation and Storage 12.2.2 Consideration of Experimental System, Focusing on Plasma and Serum 12.2.3 Obtaining and Handling Plasma for Oxylipin Analysis 12.2.4 Extraction of Oxylipins from Plasma 12.2.5 Setup of LC-MS/MS Analytical Method 12.2.6 Quality Assessment and Control 12.3 Challenges Presented by Oxylipin Isomers 12.3.1 Analytical Challenges of Isomers 12.3.2 Biological Considerations of Isomers 12.4 Analysis of Urine Oxylipin Metabolites 12.4.1 General Considerations 12.4.2 Prostaglandins (PGs) 12.5 Analysis of Oxylipins Attached to Phospholipids 12.6 Conclusions Funding Acknowledgment References 13. Mass Spectrometry for Analysis of Glycerolipids 13.1 Introduction 13.1.1 Gas Chromatography with Flame Ionization Detection for Fatty Acid Analysis 13.2 Monoacylglycerols (MAGs) 13.3 Diacylglycerols (DAGs) 13.3.1 Electrospray Ionization (ESI) for DGs 13.4 Triacylglycerols (TAGs) 13.4.1 Early Reports Described Structural Information that Comes from APCI-MS of TGs 13.4.2 Quantification of TGs by APCI-MS and APPI-MS 13.4.3 Covalent Adduct Chemical Ionization (CACI) 13.4.4 Quantification of TGs by ESI-MS Using Shotgun Lipidomics 13.4.5 Quantification of TGs by ESI-MS with HPLC/UHPLC Separation 13.4.6 Quantification of Regioisomers by ESI-MS 13.4.7 Ion Mobility MS for TGs 13.4.8 Oz-ID for TGs 13.4.9 Paternò–Büchi Reactions 13.4.10 Lipidomics 13.4.11 TG Quantification Using Lipidomics Software 13.4.12 Future Directions Acknowledgments References 14. Lipidomic Analysis of Glycerophospholipid Molecular Species in Biological Samples 14.1 Introduction 14.1.1 Diverse Functions and Structures of Glycerophospholipids 14.1.2 Pattern Recognition in Analysis of GPL 14.1.2.1 Recognition of a Building Block Pattern 14.1.2.2 Recognition of Fragmentation Patterns of GPL Classes 14.1.2.3 Molecular Mechanisms Underlying Fragmentation Patterns of GPL Classes 14.1.2.4 Practical Usage of Fragmentation Patterns of GPL Classes in Lipidomics 14.2 Fragmentation Patterns of GPL Classes 14.2.1 Choline Glycerophospholipid 14.2.1.1 Positive-Ion Mode 14.2.1.2 Negative-Ion Mode 14.2.1.3 Choline Lysoglycerophospholipids 14.2.2 Ethanolamine Glycerophospholipid 14.2.2.1 Positive-Ion Mode 14.2.2.2 Negative-Ion Mode 14.2.2.3 Phosphatidylinositol and Polyphosphoinositides 14.2.2.4 Phosphatidic Acid 14.2.2.5 Phosphatidylserine 14.2.2.6 Phosphatidylglycerol 14.2.2.7 Bis(Monoacylglycero)Phosphate 14.2.2.8 Cardiolipin 14.2.2.9 Anionic Lysoglycerophospholipids 14.2.2.10 Other Glycerophospholipids Acknowledgments References 15. Sphingolipids 15.1 Introduction 15.2 Sphingolipid Nomenclature 15.3 General Aspects of Sphingolipids in Mass Spectrometry 15.4 Sphingolipids in Vertebrates 15.4.1 Sphingoid Bases 15.4.2 Phosphorylated Sphingoid Bases 15.4.3 Ceramides Including Omega-Esterified Ceramides and 1-O-Acylceramides 15.4.3.1 Ceramides with Long and Very Long Acyl Chains 15.4.3.2 Skin Omega-Hydroxy Ceramides, Free, Esterified, and Protein-Bound 15.4.3.3 1-O-Acylceramides in Skin and Other Tissues 15.4.4 Ceramide 1-Phosphates 15.4.5 Sphingomyelins 15.4.6 Hexosylceramides 15.4.7 Neutral Complex Glycosphingolipids 15.4.8 Gangliosides 15.4.9 Sulfatides (Incl. Complex Sulfatides) 15.5 Stable Isotope Labeling 15.6 Imaging Mass Spectrometry (IMS) of Sphingolipids 15.7 Plants, Yeast, Fungi, Bacteria, Marine Organisms, and Sponges References 16. Sterol Lipids 16.1 Introduction 16.1.1 Sterol in Cells 16.1.2 Oxysterols 16.1.3 Precursors of Cholesterol 16.1.4 Sterols and Oxysterol in Blood Plasma and Serum 16.1.5 Analytical Challenges 16.2 Analytical Methods 16.2.1 Classical GC-MS Methods for Sterol and Oxysterol Analysis 16.2.2 LC-MS/MS Analysis of Sterols and Oxysterols 16.2.3 LC-MS/MS Analysis of Sterols and Oxysterols Incorporating Derivatization 16.2.3.1 Derivatization to Picolinyl and Nicotinyl Esters 16.2.3.2 Derivatization to Dimethylglycyl Esters 16.2.3.3 Derivatization with Girard Hydrazine Reagents 16.2.3.4 Derivatization with 4-Phenyl-1,2,4-triazoline-3,5-dione (PTAD) 16.2.4 Mass Spectrometry Imaging of Cholesterol and Oxysterols in Tissue 16.2.5 Analysis of Steryl Esters 16.3 Conclusions Acknowledgments Conflict of Interest Statement References 17. Bile Acids 17.1 Introduction 17.2 Analytical Methods and Applications 17.2.1 Gas Chromatography–Mass Spectrometry (GC-MS) 17.2.2 Liquid Chromatography–Mass Spectrometry (LC-MS) 17.2.2.1 Early Technologies and ESI-Quadrupole MS 17.2.2.2 High-Resolution Mass Spectrometry (HR-MS) 17.2.3 Supercritical Fluid Chromatography (SFC) 17.3 Conclusions and Outlook References Part III: Lipidomic Applications 18. Lipidomic Profiling in a Large-Scale Cohort 18.1 Lipidomic Profiling in a Large-Scale Cohort Project 18.2 Sample Collection 18.3 Sample Preparation 18.3.1 Analytical Platform 18.3.2 Data Acquisition 18.3.3 Data Processing 18.3.4 Database Creation 18.3.5 Combination of Genome-Wide Association Studies 18.4 Conclusion References 19. Cancer Lipidomics – From the Perspective of Analytical Chemists 19.1 Introduction 19.2 Investigating Dysregulated Lipids in Biological Samples 19.3 Samples 19.4 Preanalytical Considerations 19.5 Sample Preparation 19.6 Method Requirements 19.7 Validation and Quality Control 19.8 Data Processing, Statistical Analysis, and Data Reporting 19.9 Lipidomic Analysis in Cancer Research References 20. Lipidomics in Clinical Diagnostics 20.1 What Do We Mean by “Clinical Diagnostics”? 20.2 Mass Spectrometry as an Enabler for Lipid-Based Clinical Tests 20.2.1 Vitamin D and Its Metabolites 20.2.2 The Trailblazing Ceramides 20.3 Bringing Lipidomics to the Clinic: Overcoming Current Challenges and Barriers 20.3.1 Raison D’être for Lipidomics in Patient Care: What Is the Clinical Utility? 20.3.2 The Reproducibility Issue: Is It Time to Harmonize? 20.3.3 From Consensus Values to Reference Intervals and True Values 20.4 Examples of Currently Existing Diagnostic Applications 20.4.1 Mitochondrial Fatty Acid -Oxidation and Organic Acid Metabolism 20.4.2 Fabry Disease 20.4.3 Gaucher Disease 20.4.4 Minimally Invasive Diagnostic Testing for NAFLD/NASH 20.4.5 Intrahepatic Cholestasis of Pregnancy 20.4.6 Steroid Hormone Measurements for CAH and Vitamin D Deficiency 20.4.6.1 Congenital Adrenal Hyperplasia 20.4.6.2 Vitamin D Deficiency 20.4.7 F2-Isoprostanes as Markers of Oxidative Stress 20.5 Final Comments References 21. Lipidomics in Food Industry and Nutrition 21.1 Introduction 21.2 Lipids in Nutrition and Human Health 21.3 Fish, Shellfish, and Algae: Main Food Sources of Omega-3 21.4 Edible Plants and Vegetable Oils: Main Food Sources of Omega-6 21.5 Concluding Remarks References 22. Lipidomics in Plant Science 22.1 Introduction 22.2 The Role of Phosphatidic Acid in Plant Response to Nutrients and Stress 22.3 The Roles of Phospholipids in Flowering and Diurnal Metabolism 22.4 Sphingolipid Analysis Has Facilitated the Discovery of Pathways Regulating Important Plant Cell Functions 22.5 Identification of a New Lipid Class in Plants Under Phosphate Stress 22.6 Oxidation and Head-Group Acylation of Membrane Lipids in Plant Stress 22.7 Triacylglycerols in Seeds and Leaves 22.8 Lipidomics to Monitor the Progress of Genetic Engineering to Alter Plant TG Level or Composition 22.9 The Future of Lipidomics in Plant Science Acknowledgments References 23. Lipidomics in Multi-Omics Studies 23.1 Introduction 23.2 Lipidomics in Multi-Omics Studies 23.3 Planning and Conducting Multi-Omics Studies 23.4 Analyzing Multi-Omics Data 23.5 Current Challenges 23.6 Conclusions and Outlook References 24. Tracer Lipidomics 24.1 Flux Analysis and Stable Isotope Labeling Patterns 24.2 Experimental Conditions and Selecting the Right Tracer 24.3 Targeted Tracer Analysis 24.3.1 Fatty Acids 24.3.2 Phospholipids 24.4 Toward Untargeted Lipidome-Wide Tracer Analysis 24.4.1 Isotopic Effects and the Complexity of Tracer Analysis Mass Spectra 24.4.2 Technical Considerations 24.5 MS/MS Analysis as a Unique Approach to Study Fluxes at the Molecular Species Level 24.6 Concluding Remarks References 25. Mass Spectrometry for Lipidomics: Methods and Applications – Aging and Alzheimer’s Disease 25.1 Introduction 25.2 Diversity in the Aging Process 25.3 Using Lipidomics as a Tool to Examine the Diversity in Aging 25.4 Age-Related Changes to the Plasma Lipidome 25.5 Age Is the Biggest Risk Factor for Alzheimer’s Disease 25.6 Interplay Between Lipids and Alzheimer’s Disease 25.7 Concept of Chronological and Metabolic Age 25.8 Development and Application of a Lipidomic Metabolic Age Score: The Next Steps 25.9 Conclusion References 26. Lipidomics in Cell Biology 26.1 Lipid Composition of Organelles 26.1.1 Metabolic Bias Depending Upon Subcellular Location 26.1.2 Correlation Between Lipid Composition and Membrane Biophysical Properties 26.2 Lipid Composition Dictates Mechanisms of Intracellular Trafficking 26.2.1 The Endocytic Pathway 26.2.2 The Early Secretory Pathway 26.3 Multiomic Approaches to Investigate Cell Biology 26.4 Perspectives References 27. Microbial Lipidomics 27.1 Introduction 27.2 Diversity of Lipid Structures in Intestinal Bacteria and Analytical Methods Using Mass Spectrometry 27.2.1 Fatty Acids 27.2.2 Glycerophospholipids 27.2.3 Sphingolipids 27.2.4 Bile Acids 27.2.5 Saccharolipids 27.3 New MS Technology 27.3.1 Chromatography Technology 27.3.2 Fragmentation 27.3.3 Identification Method for Unknown Structural Molecules 27.4 Conclusion and Future Perspective References Index