Mass Spectrometry

Rolf Ekman, PhD, is a Professor of Neurochemistry at University of Gothenburg in Sweden. JERZY SILBERRING, PhD, is the Head of the Department of Neurobiochemistry in the Department of Chemistry and the former deputy head of the Regional Laboratory of Physicochemical Analyses at Jagiellonian University in Krakow, Poland.Ann M. Westman-Brinkmalm, PhD, is a Junior Research Fellow at the Sahlgrenska Academy at University of Gothenburg in Sweden.Agnieszka Kraj, PhD, is an Assistant Professor in the Department of Neurobiochemistry, Faculty of Chemistry at Jagiellonian University in Krakow, Poland.

• Foreword xiiiContributors xvPart I Instrumentation 11 Definitions and Explanations 3Ann Westman-Brinkmalm and Gunnar BrinkmalmReferences 132 A Mass Spectrometer’s Building Blocks 15Ann Westman-Brinkmalm and Gunnar Brinkmalm2.1. Ion Sources 152.1.1. Gas Discharge 162.1.2. Thermal Ionization 162.1.3. Spark Source 192.1.4. Glow Discharge 202.1.5. Inductively Coupled Plasma 212.1.6. Electron Ionization 232.1.7. Chemical Ionization 242.1.8. Atmospheric Pressure Chemical Ionization 242.1.9. Photoionization 252.1.10. Multiphoton Ionization 252.1.11. Atmospheric Pressure Photoionization 262.1.12. Field Ionization 262.1.13. Field Desorption 272.1.14. Thermospray Ionization 272.1.15. Electrospray Ionization 272.1.16. Desorption Electrospray Ionization 292.1.17. Direct Analysis in Real Time 302.1.18. Secondary Ion Mass Spectrometry 312.1.19. Fast Atom Bombardment 332.1.20. Plasma Desorption 342.1.21. Laser Desorption/Ionization 342.1.22. Matrix-Assisted Laser Desorption/Ionization 352.1.23. Atmospheric Pressure Matrix-Assisted Laser Desorption/Ionization 372.2. Mass Analyzers 382.2.1. Time-of-Flight 402.2.2. Magnetic/Electric Sector 452.2.3. Quadrupole Mass Filter 492.2.4. Quadrupole Ion Trap 512.2.5. Orbitrap 552.2.6. Fourier Transform Ion Cyclotron Resonance 582.2.7. Accelerator Mass Spectrometry 622.3. Detectors 652.3.1. Photoplate Detector 652.3.2. Faraday Detector 672.3.3. Electron Multipliers 672.3.4. Focal Plane Detector 692.3.5. Scintillation Detector 692.3.6. Cryogenic Detector 702.3.7. Solid-State Detector 702.3.8. Image Current Detection 70References 713 Tandem Mass Spectrometry 89Ann Westman-Brinkmalm and Gunnar Brinkmalm3.1. Tandem MS Analyzer Combinations 913.1.1. Tandem-in-Space 913.1.2. Tandem-in-Time 953.1.3. Other Tandem MS Configurations 973.2. Ion Activation Methods 973.2.1. In-Source Decay 973.2.2. Post-Source Decay 983.2.3. Collision Induced/Activated Dissociation 983.2.4. Photodissociation 1003.2.5. Blackbody Infrared Radiative Dissociation 1003.2.6. Electron Capture Dissociation 1013.2.7. Electron Transfer Dissociation 1013.2.8. Surface-Induced Dissociation 101References 1024 Separation Methods 105Ann Westman-Brinkmalm, Jerzy Silberring, and Gunnar Brinkmalm4.1. Chromatography 1064.1.1. Gas Chromatography 1064.1.2. Liquid Chromatography 1074.1.3. Supercritical Fluid Chromatography 1094.2. Electric-Field Driven Separations 1104.2.1. Ion Mobility 1104.2.2. Electrophoresis 111References 113Part II Interpretation 1175 Introduction to Mass Spectra Interpretation: Organic Chemistry 119Albert T. Lebedev5.1. Basic Concepts 1195.2. Inlet Systems 1215.2.1. Direct Inlet 1215.2.2. Chromatography-Mass Spectrometry 1215.3. Physical Bases of Mass Spectrometry 1285.3.1. Electron Ionization 1295.3.2. Basics of Fragmentation Processes in Mass Spectrometry 1305.3.3. Metastable Ions 1355.4. Theoretical Rules and Approaches to Interpret Mass Spectra 1375.4.1. Stability of Charged and Neutral Particles 1375.4.2. The Concept of Charge and Unpaired Electron Localization 1485.4.3. Charge Remote Fragmentation 1515.5. Practical Approaches to Interpret Mass Spectra 1525.5.1. Molecular Ion 1525.5.2. High Resolution Mass Spectrometry 1555.5.3. Determination of the Elemental Composition of Ions on the Basis of Isotopic Peaks 1585.5.4. The Nitrogen Rule 1645.5.5. Establishing the 13 C Isotope Content in Natural Samples 1665.5.6. Calculation of the Isotopic Purity of Samples 1665.5.7. Fragment Ions 1685.5.8. Mass Spectral Libraries 1735.5.9. Additional Mass Spectral Information 1735.5.10. Fragmentation Scheme 175References 1776 Sequencing of Peptides and Proteins 179Marek Noga, Tomasz Dylag, and Jerzy Silberring6.1. Basic Concepts 1796.2. Tandem Mass Spectrometry of Peptides and Proteins 1816.3. Peptide Fragmentation Nomenclature 1836.3.1. Roepstorff’s Nomenclature 1836.3.2. Biemann’s Nomenclature 1856.3.3. Cyclic Peptides 1876.4. Technical Aspects and Fragmentation Rules 1886.5. Why Peptide Sequencing? 1906.6. De Novo Sequencing 1926.6.1. Data Acquisition 1936.6.2. Sequencing Procedure Examples 1946.6.3. Tips and Tricks 2056.7. Peptide Derivatization Prior to Fragmentation 2076.7.1. Simplification of Fragmentation Patterns 2086.7.2. Stable Isotopes Labeling 209Acknowledgments 210References 210Online Tutorials 2107 Optimizing Sensitivity and Specificity in Mass Spectrometric Proteome Analysis 211Jan Eriksson and David Fenyö7.1. Quantitation 2127.2. Peptide and Protein Identification 2137.3. Success Rate and Relative Dynamic Range 2187.4. Summary 220References 220Part III Applications 2238 Doping Control 225Graham TroutReferences 2339 Oceanography 235R. Timothy Short, Robert H. Byrne, David Hollander, Johan Schijf, Strawn K. Toler, and Edward S. VanVleetReferences 24110 “omics” Applications 243Simone König10.1. Introduction 24310.2. Genomics and Transcriptomics 24610.3. Proteomics 24810.4. Metabolomics 25111 Space Sciences 253Robert Sheldon11.1. Introduction 25311.2. Origins 25411.3. Dynamics 25611.4. The Space MS Paradox 25711.5. A Brief History of Space MS 25911.5.1. Beginnings 25911.5.2. Linear TOF-MS 26011.5.3. Isochronous TOF-MS 26211.6. GENESIS and the Future 264References 26412 Bioterrorism 267Vito G. DelVecchio and Cesar V. Mujer12.1. What is Bioterrorism? 26712.2. Some Historical Accounts of Bioterrorism 26712.3. Geneva Protocol of 1925 and Biological Weapons Convention of 1972 26812.4. Categories of Biothreat Agents 26812.5. Challenges 26912.6. MS Identification of Biomarker Proteins 27012.7. Development of New Therapeutics and Vaccines Using Immunoproteomics 271References 27213 Imaging of Small Molecules 275Małgorzata Iwona Szynkowska13.1. SIMS Imaging 27713.2. Biological Applications (Cells, Tissues, and Pharmaceuticals) 27813.3. Catalysis 28013.4. Forensics 28113.5. Semiconductors 28213.6. The Future 283References 28514 Utilization of Mass Spectrometry In Clinical Chemistry 287Donald H. Chace14.1. Introduction 28714.2. Where are Mass Spectrometers Utilized in Clinical Applications? 28814.3. Most Common Analytes Detected by Mass Spectrometers 28814.4. Multianalyte Detection of Clinical Biomarkers, The Real Success Story 28914.5. Quantitative Profiling 29114.6. A Clinical Example of the Use of Mass Spectrometry 29214.7. Demonstrations of Concepts of Quantification in Clinical Chemistry 29414.7.1. Tandem Mass Spectrometry and Sorting (Pocket Change) 29414.7.2. Isotope Dilution and Quantification (the Jelly Bean Experiment) 29515 Polymers 299Maurizio S. Montaudo15.1. Introduction 29915.2. Instrumentation, Sample Preparation, and Matrices 30015.3. Analysis of Ultrapure Polymer Samples 30115.4. Analysis of Polymer Samples in which all Chains Possess the Same Backbone 30115.5. Analysis of Polymer Mixtures with Different Backbones 30315.6. Determination of Average Molar Masses 303References 30616 Forensic Sciences 309Maria Kala16.1. Introduction 30916.2. Materials Examined and Goals of Analysis 31116.3. Sample Preparation 31216.4. Systematic Toxicological Analysis 31216.4.1. GC-MS Procedures 31516.4.2. LC-MS Procedures 31516.5. Quantitative Analysis 31716.6. Identification of Arsons 319References 31917 New Approaches to Neurochemistry 321Jonas Bergquist, Jerzy Silberring, and Rolf Ekman17.1. Introduction 32117.2. Why is there so Little Research in this Area? 32217.3. Proteomics and Neurochemistry 32317.3.1. The Synapse 32417.3.2. Learning and Memory 32417.3.3. The Brain and the Immune System 32517.3.4. Stress and Anxiety 32717.3.5. Psychiatric Diseases and Disorders 32917.3.6. Chronic Fatigue Syndrome 32917.3.7. Addiction 33017.3.8. Pain 33117.3.9. Neurodegenerative Diseases 33117.4. Conclusions 333Acknowledgments 333References 334Part IV Appendix 337Index 353

"It was my great pleasure to read this clearly written and well organized mass spectrometry (MS) book. In view, it can serve as an excellent textbook for both undergraduate and graduate students who major in analytical, biological, forensic, or environmental chemistry, as well as a valuable resource to those researchers who are interested in the MS-based chemical analysis." (J Am Soc Mass Spectrom, 2011) "The book is particularly designed for graduate students, with the assumption being made that most of them will not become mass spectrometry specialists. Instead, it focuses on how they can use the technique to support and advance research across a broad range of disciplines." (Chemistry Journals, 11 April 2011)