Fundamentals of Contemporary Mass Spectrometry

ISBN-13: 9780471682295 / Angielski / Twarda / 2007 / 608 str.

Chhabil Dass

Opis

Modern mass spectrometry - the instrumentation and applications in diverse fields Mass spectrometry has played a pivotal role in a variety of scientific disciplines. Today it is an integral part of proteomics and drug discovery process. Fundamentals of Contemporary Mass Spectrometry gives readers a concise and authoritative overview of modern mass spectrometry instrumentation, techniques, and applications, including the latest developments. After an introduction to the history of mass spectrometry and the basic underlying concepts, it covers:

• Instrumentation, including modes of ionization, condensed phase ionization techniques, mass analysis and ion detection, tandem mass spectrometry, and hyphenated separation techniques
• Organic and inorganic mass spectrometry
• Biological mass spectrometry, including the analysis of proteins and peptides, oligosaccharides, lipids, oligonucleotides, and other biological materials
• Applications to quantitative analysis

Based on proven teaching principles, each chapter is complete with a concise overview, highlighted key points, practice exercises, and references to additional resources. Hints and solutions to the exercises are provided in an appendix. To facilitate learning and improve problem-solving skills, several worked-out examples are included. This is a great textbook for graduate students in chemistry, and a robust, practical resource for researchers and scientists, professors, laboratory managers, technicians, and others. It gives scientists in diverse disciplines a practical foundation in modern mass spectrometry.

Recenzje

It presents a well written, informative, and welcome addition to the selection of textbooks on the topic. ( Analytical Science and Bioanalytical Chemistry, August 2007)

"The book will be a good teaching tool of the principles of mass spectrometry to undergraduates and graduates." (International Journal of Environmental and Analytical Chemistry, 2008)

Spis treści

PART 1: INSTRUMENTATION. 1. BASICS OF MASS SPECTROMETRY. 1.1. A BRIEF HISTORY OF MASS SPECTROMETRY. 1.2. UNIQUE FEATURES OF MASS SPECTROMETRY. 1.3. BASIC PRINCIPLES OF MASS SPECTROMETRY. 1.4. ANATOMY OF A MASS SPECTRUM. 1.5. ATOMIC AND MOLECULAR MASSES. 1.5.1. Mass–to–charge Ratio. 1.6. GENERAL APPLICATIONS. 1.7. OVERVIEW OF THE CHAPTER. 1.8. EXCERCISES. 1.9. REFERENCES. 2. MODES OF IONIZATION. 2.1. WHY IONIZATION IS REQUIRED? 2.2. GENERAL CONSTRUCTION OF THE ION SOURCE. GAS–PHASE IONIZATION TECHNIQUES. 2.3. ELECTRON IONIZATION. 2.4. CHEMICAL IONIZATION. 2.4.1. Charge–exchange Chemical Ionization. 2.4.2. Negative–Ion Chemical Ionization. 2.5. PHOTOIONIZATION. 2.6. FIELD IONIZTION. 2.7. METASTABLE ATOM BOMBARDMENT IONIZATION. CONDENSED–PHASE IONIZATION TECHNIQUES: IONIZATION OF SOLID–STATE SAMPLES. 2.8. FIELD DESORPTION. 2.9. PLASMA DESORPTION IONIZATION. 2.10. SECONDARY–ION MASS SPECTROMETRY . 2.11. FAST ATOM BOMBARDMENT. 2.12. LASER DESORPTION/IONIZATION. 2.13. MATRIX–ASSISTED LASER DESORPTION/IONIZATION. 2.13.1. Analysis of Low Molecular Mass Compounds by MALDI . 2.13.2. Atmospheric Pressure–MALDI. 2.13.3. Surface–enhanced Laser Desorption/Ionization. CONDENSED–PHASE IONIZATION TECHNIQUES: IONIZATION OF LIQUID–STATE SAMPLES . 2.14. THERMOSPRAY IONIZATION. 2.15. ATMOSPHERIC PRESSURE CHEMICAL IONIZATION. 2.16. ATMOSPHERIC PRESSURE PHOTOIONIZATION. 2.17. ELECTROSPRAY IONIZATION. 2.17.1. Mechanism of Electrospray Ionization . 2.17.2. Sample Consideration . 2.17.3. Nanoelectrospray Ionization . 2.18. DESORPTION ELECTROSPRAY IONIZATION. 2.18.1. DART Ion Source. 2.19. OVERVIEW OF THE CHAPTER. 2.19. EXERCISES. 2.20. ADDITIONAL READING. 2.21. REFERENCES. 3. MASS ANALYSIS AND ION DETECTION. 3.1. MASS RESOLUTION. 3.2. KINETIC ENERGY OF IONS. MASS ANALYZERS. 3.3. MAGNETIC SECTOR MASS SPECTROMETERS. 3.3.1. Working Principle of a Magnetic Analyzer. 3.3.2. Working Principle of an Electrostatic Analyzer. 3.3.3. Working Principle of Double–Focusing Magnetic Sector Mass Spectrometers. 3.3.4. Performance Characteristics . 3.4. QUADRUPOLE MASS SPCETROMETERS. 3.4.1. Working Principle. 3.4.2. Performance Characteristics . 3.4.3. RF–only quadrupole . 3.5. TIME–OF–FLIGHT MASS SPECTROMETERS. 3.5.1. Working Principle. 3.5.2. Delayed Extraction of Ions . 3.5.3. Reflectron TOF Instrument . 3.5.4. Orthogonal Acceleration TOF Mass Spectrometer. 3.5.5. Performance Characteristics. 3.6. QUADRUPOLE ION TRAP MASS SPECTROMETERS. 3.6.1. Working Principle. 3.6.2. Operational Modes. 3.6.3. Performance Characteristics . 3.7. LINEAR ION TRAP MASS SPECTROMETERS. 3.7.1. Rectilinear Ion Trap. 3.8. FOURIER–TRANSFORM ION CYCLOTRON RESONANCE MASS SPECTROMETERS. 3.8.1. Working Principle. 3.8.2. Performance Characteristics. 3.9. ORBITRAP MASS ANALYZER. 3.10. ION MOBILITY MASS SPECTROMETERS. 3.11. DETECTORS. 3.11.1. Faraday Cup Detector. 3.11.2. Electron Multipliers. 3.11.3. Photomultiplier detectors. 3.11.4. Post–acceleration Detectors. 3.11.5. Low–temperature Calorimetric Detectors for High Mass Ions. 3.11.6. Focal–plane Detectors. 3.12. OVERVIEW OF THE CHAPTER. 3. 13. EXCERCISES. 3. 14. ADDITIONAL READING. 3.15. REFERENCES. 4. TANDEM MASS SPECTROMETRY. 4.1. BASIC PRINCIPLES OF TANDEM MASS SPECTROMETRY. 4.2. TYPES OF SCAN FUNCTIONS. 4.3. ION ACTIVATION AND DISSOCIATION. 4.3.1. Collision–induced Dissociation. 4.3.2. Surface–induced Dissociation. 4.3.3. Absorption of Electromagnetic Radiations. 4.3.4. Electron–capture Dissociation. 4.4. REACTIONS IN TANDEM MASS SPECTROMETRY. 4.5. TANDEM MASS SPECTROMETRY INSTRUMENTATION. 4.5.1. Magnetic Sector Tandem Mass Spectrometers. 4.5.2. Tandem Mass Spectrometry with Multiple Quadrupole Devices. 4.5.3. Tandem Mass Spectrometry with Time–of–Flight Instruments . 4.5.4. Tandem Mass Spectrometry with a Quadrupole Ion Trap Mass Spectrometer. 4.5.5. Tandem Mass Spectrometry with an FT–ICR Mass Spectrometer. 4.5.6. Tandem Mass Spectrometry with Hybrid Instruments. 4.6. OVERVIEW OF THE CHAPTER. 4.7. EXCERCISES. 4.7. ADDITIONAL READING. 4.8. REFERENCES. 5. HYPHENATED SEPARATION TECHNIQUES. 5.1. BENEFITS OF THE COUPLING OF SEPARATION DEVICES WITH MASS SPECTROMETRY. 5.2. GENERAL CONSIDERATIONS. 5.2.1. Characteristics of an Interface. 5.2.2. Mass Spectral Data Acquisition. 5.2.3. Characteristics of Mass Spectrometers. 5.3. CHROMATOGRAPHIC PROPERTIES. 5.4. GAS CHROMATOGRAPHY/MASS SPCTROMETRY. 5.4.1 Basic Principles of Gas Chromatography. 5.4.2 Interfaces for the Coupling of Gas Chromatography with Mass Spectrometry. 5.5. LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY. 5.5.1. Basic Principle of HPLC Separation . 5.5.2 Fast–Flow Liquid Chromatography. 5.6. INTERFACES FOR THE COUPLING OF LIQUID CHROMATO–GRAPHY WITH MASS SPECTROMETRY. 5.6.1. The Moving–belt Interface. 5.6.2. The Direct–Liquid Introduction Probe . 5.6.3. The Continuous–Flow Fast Atom Bombardment Interface. 5.6.4. The Thermospray Interface. 5.6.5. The Particle–beam Interface. 5.6.6. The Electrospray Ionization Interface. 5.6.7. The Atmospheric Pressure Chemical Ionization Interface. 5.6.8. The Atmospheric Pressure Photoionization (APPI) Interface. 5.6.9. The Coupling of LC with TOF–MS. 5.6.10. The Coupling of LC with MALDI–MS. 5.7. MULTI–DIMENSIONAL LC/MS. 5.8. CAPILLARY ELECTROPHORESIS/MASS SPECTROMETRY. 5.8.1. The Basic Principles of Capillary Electrophoresis. 5.8.2. Interfaces for the Coupling of Capillary Electrophoresis with Mass Spectrometry. 5.9. AFFINITY CHROMATOGRAPHY/MASS SPECTROMETRY . 5.10. SUPERCRITICAL–FLUID CHROMATOGRAPHY/MASS SPECTROMETRY. 5.11. THE COUPLING OF PLANAR CHROMATOGRAPHY WITH MASS SPECTROMETRY. 5.12. OVERVIEW OF THE CHAPTER. 5.13. EXCERCISES. 5.14. ADDITIONAL READING. 5.15. REFERENCES. PART 2: ORGANIC AND INORGAANIC MASS SPECTROMETRY . 6. ORGANIC MASS SPECTROMETRY. 6.1. DETERMINATION OF MOLECULAR MASS. 6.1.1. Molecular Mass Measurements at Low–mass Resolving Power. 6.1.2. Molecular Mass Measurements at High–mass Resolving Power . 6.1.3. Molecular Mass Measurements by ESI and MALDI. 6.1.4. Mass Calibration Standards. 6.2. MOLECULAR FORMULA FROM ACCURATE MASS VALUES . 6.3. MOLECULAR FORMULA FROM ISOTOPIC PEAKS. 6.4. GENERAL GUIDELINES FOR THE INTERPRETATION OF A MASS SPECTRUM . 6.4.1. Odd– and Even–electron Ions. 6.4.2. Recognize the Molecular Ion. 6.4.3. The Nitrogen Rule . 6.4.4. The Rings Plus Double Bonds (R + DB) Value . 6.4.5. Systematic Steps to Interpret a Mass Spectrum. 6.4.6. Mass Spectral Compilations. 6.5. FRAGMENTATION PROCESSES. 6.5.1. Simple Bond–cleavage Reactions. 6.5.2. Rearrangement Reactions. 6.5.3. Fragmentation of Cyclic Structures. 6.5.4. Differentiation of Isomeric Structures. 6.5.5. Structurally Diagnostic Fragment Ions. 6.6. FRAGMENTATION REACTIONS OF SPECIFIC CLASSES OF COMPOUNDS. 6.6.1. Hydrocarbons. 6.6. FRAGMENTATION REACTIONS OF SPECIFIC CLASSES OF COMPOUNDS. 6.6.1. Hydrocarbons. 6.6. FRAGMENTATION REACTIONS OF SPECIFIC CLASSES OF COMPOUNDS. 6.6.1. Hydrocarbons. 6.6.2. Alcohols. 6.6.3. Ethers. 6.6.4. Aldehydes and Ketones. 6.6.5. Carboxylic Acids. 6.6.6. Esters. 6.6.7. Nitrogen–containing Compounds6.6.8. Sulfur–containing Compounds. 6.6.8. Sulfur–containing Compounds. 6.6.9. Halogen–containing Compounds. 6.7. THEORY OF ION DISSOCIATION. 6.8. STRUCTURE DETERMINATION OF GAS–PHASE ORGANIC IONS. 6.9. OVERVIEW OF THE CHAPTER. 6. 10. EXCERCISES. 6.11. ADDITIONAL READING. 6.12. REFERENCES. 7. INORGANIC MASS SPECTROMETRY. 7.1. IONIZTION OF INORGANIC COMPOUNDS. 7.2. THERMAL IONIZATION MASS SPECTROMETRY. 7.3. SPARK–SOURCE MASS SPECTROMETRY (SSMS). 7.4. GLOW DISCHARGE IONIZATION MASS SPECTROMETRY. 7.5. INDUCTIVELY COUPLED PLASMA MASS SPECTROMETRY. 7.5.1. Inductively Coupled Plasma Ion Source . 7.5.2. Coupling of the ICP Source with Mass Spectrometry . 7.5.3. Sample Introduction Systems for the ICP Source. 7.5.4. Spectral Interferences. 7.5.5. Laser Ablation–ICPMS. 7.6. RESONANCE IONIZATION MASS SPCTROMETRY. 7.7. ISOTOPE RATIO MASS SPCTROMETRY. 7.7.1. Isotope Ratio MS Systems . 7.8. ACCELERATOR MASS SPECTROMETRY. 7.9. ISOTOPE DILUTION MASS SPECTROMETRY. 7.10. OVERVIEW OF THE CHAPTER. 7.11. EXCERCISES. 7.12. ADDITIONAL READING. 7.13. REFERENCES. PART 3: BIOLOGICAL MASS SPECTROMETRY. 8. PROTEINS AND PEPTIDES: STRUCTURE DETERMINATION. 8.1. INTRODUCTION . 8.1.1. Structure of Proteins . 8.2. DETERMINATION OF THE SEQUENCE OF A PROTEIN. 8.3. GENERAL PROTOCOL FOR THE AMINO ACID SEQUENCE DETERMINATION OF PROTEINS . 8.3.1. Homogenization and Subcellular Fractionation. 8.3.2. Enrichment and Purification of Proteins. 8.4. MOLECULAR MASS MEASUREMENT OF PROTEINS. 8.5. PEPTIDE MASS MAPPING. 8.5.1. Reduction and Carboxymethylation. 8.5.2. Cleavage of Proteins. 8.5.3. Mass Spectrometry Analysis of Peptide Maps . 8.6. PROTEOMICS. 8.6.1. Strategies for Proteomics. 8.7. QUANTITATIVE PROTEOMICS. 8.8. BIOMARKER DISCOVERY. 8.9. DE NOVO PROTEIN SEQUENCING . 8.9. DETERMINATION OF THE AMINO ACID SEQUENCE OF PEPTIDES. 8.9.1. Peptide Fragmentation Rules . 8.9.2. Mass Spectrometry Techniques for Sequence Determination of Peptides. 8.9.3. Guidelines to Obtain the Amino Acid Sequence from a Mass Spectrum. 8.10. OVERVIEW OF THE CHAPTER. 8.11. EXCERCISES. 8.12. ADDITIONAL READING. 8.13. REFERENCES. 9. Proteins and Peptides: Post–Translational Modifications Disulfide Bonds in Proteins. 9.1. TRADITIONAL APPROACHES TO IDENTIFY DISULFIDE BONDS . 9.2. MASS SPECTROMETRY–BASED METHODS TO IDENTIFY DISULFIDE BONDS. 9.2.1. Determination of the Number of Disulfide Bonds . 9.2.2. Generation of the Disulfide–containing Peptides . 9.2.3. Identification of Disulfide–containing Peptides by FAB–MS . 9.2.4. Identification of the Disulfide–containing Peptides by MALDI–MS . 9.2.5. Identification of the Disulfide–containing Peptides by Electron–capture Dissociation (ECD) . 9.2.6. Identification of Disulfide–containing Peptides by Tandem MS . ANALYSIS OF PHOPHOPROTEINS AND PHOSPHO–PROTEOMICS. 9.3. 32[P]–Labeling for the Analysis of Phosphoproteins. 9.4. MASS SPECTROMETRY PROTOCOL FOR THE ANALYSIS OF PHOSPHOPROTEINS. 9.4.1. Cleavage of Purified Phosphoproteins . 9.4.2. Fractionation of Peptide Fragments in the Digest . 9.4.3. Determination of the Average Number of Phosphate Groups . 9.4.4. Identification of Phosphopeptides . 9.4.5. Identification of Phosphorylation Sites . ANALYSIS OF GLYCOPROTEINS. 9.5. STRUCTURAL DIVERSITY OF GLYCOPROTEINS. 9.6. ANALYSIS OF GLYCOPROTEINS. 9.6.1. Molecular Mass Determination of Glycoproteins. 9.6.2. Identification of Glycosylation. 9.6.3. Site of Glycosylation . 9.7. OVERVIEW OF THE CHAPTER. 9.8. EXCERCISES. 9.9. REFERENCES. 10. Proteins and Peptides: Higher–Order Structures. 10.1. CHARGE–STATE DISTRIBUTION. 10.2. HYDROGEN/DEUTERIUM EXCHANGE TO STUDY CONFORMATIONAL STATES OF PROTEINS. 10.2.1. Folding/Unfolding Dynamics of Proteins. 10.2.2. Experimental Measurements of the Amide Hydrogen Isotopic Exchange . 10.3. CHEMICAL CROSS–LINKING AS A PROBE FOR THE 3–D STRUCTURE OF PROTEINS. 10.4. ION MOBILITY MEASUREMENTS TO STUDY PROTEIN CONFORMATIONAL CHANGES. 10.5. OVERVIEW OF THE CHAPTER. 10.6. EXCERCISES. 10.7. ADDITIONAL READING. 10.8. REFERENCES. 11. Characterization of Oligosaccharides. 11.1. STRUCTURAL DIVERSITY IN OLIGOSACCHARIDES. 11.2. CLASSES OF GLYCANS. 11.3. MASS SPECTROMETRIC METHODS FOR COMPLETE STRCUTURE ELUCIDATION OF OLIGOSACCHARIDES. 11.3.1. Release of Glycans. 11.3.2. Derivatization of Carbohydrate chains. 11.3.3. Composition Analysis by GC/MS. 11.3.4. Linkage Analysis by GC/MS. 11.3.5. Rapid Identification by a Precursor–ion Scan . 11.3.6. Composition Analysis by Direct Mass Measurement. 11.3.7. Structure Determination of Oligosaccharides by Sequential Digestion. 11.3.8. Tandem Mass Spectrometry for Structural Analysis of Carbohydrates. 11.4. OVERVIEW OF THE CHAPTER. 11.5. EXCERCISES. 11.6. REFERENCES. 12. Characterization of Lipids. 12.1. CLASSIFICATION AND STRUCTURES OF LIPIDS. 12.2. MASS SPECTROMETRY OF FATTY ACIDS AND ACYLGLYCEROLS. 12.2.1. Analysis of Fatty Acids. 12.2.2. Analysis of Acylglycerols. 12.3. MASS SPECTROMETRY OF PHOSPHOLIPIDS. 12.4. MASS SPECTROMETRY OF GLYCOLIPIDS. 12.5. ANALYSIS OF BILE ACIDS AND STEROIDS. 12.6. ANALYSIS OF EICOSANOIDS. 12.7. LIPIDOMICS. 12.8. OVERVIEW OF THE CHAPTER. 12.9. EXCERCISES . 12.10. REFERENCES. 13. Structure Determination of Oligonucleotides. 13.1. STRUCTURES OF NUCLEOTIDES AND OLIGONUCLEOTIDES. 13.2. MASS SPECTROMETRY ANALYSIS OF NUCLEOSIDES AND NUCLEOTIDES. 13.3. CLEAVAGE OF OLIGONUCLEOTIDES. 13.4. MOLECULAR MASS DETERMINATION OF OLIGONUCLEOTIDES. 13.4.1. Electrospray Ionization for the Molecular Mass Determination . 13.4.2. Matrix–assisted Laser Desorption/Ionization for Molecular Mass Determination. 13.4.3. Base Composition from an Accurate Mass Measurement. 13.5. MASS SPECTROMETRY SEQUENCING OF OLIGONUCLEAOTIDES. 13.5.1. Gas–phase Fragmentation for Oligonucleotide Sequencing. 13.5.2. Solution–phase Techniques for Oligonucleotide Sequencing . 13.6. OVERVIEW OF THE CHAPTER. 13.7. EXCERCISES. 13.8. REFERENCES. 14. Quantitative Analysis. 14.1. ADVANTAGES OF MASS SPECTROMETRY. 14.2. DATA ACQUISITION. 14.2.1. Selected–ion Monitoring. 14.2.2. Selected–reaction Monitoring. 14.3. CALIBRATION. 14.3.1. External Standard Method. 14.3.2. Standard Addition Method. 14.3.3. Internal Standard Method . 14.4 VALIDATION OF A QUANTITATIVE METHOD. 14.5. SELECTED EXAMPLES. 14.5.1. Applications of Gas Chromatography/Mass Spectrometry. 14.5.2. Applications of Liquid Chromatography/Mass Spectrometry . 14.5.3. Applications of MALDI–MS. 14.6. OVERVIW OF THE CHAPTER. 14.7. EXCERCISES. 14.8. ADDITIONAL READING. 14.9. REFERENCES. 15. Misclaneous Topics. 15.1. ENZYME KINETICS. 15.1.1. Theory. 15.1.2. Reaction Monitoring. 15.2. IMAGING MASS SPECTROMETRY. 15.2.2. Imaging with SIMS. 15.2.2. Imaging with MALDI–MS. 15.3. ANALYSIS OF MICROORGANISMS. 15.3.1. Bacterial Identification. 15.3.2. Analysis of Viruses. 15.4. CLINICAL MASS SPECTROMETRY. 15.4.1. Low Molecular Mass Compounds as Biomarkers of Disease. 15.4.2. Analysis of DNA to diagnose Genetic Disorders. 15.4.3. Proteins as Biomarkers of Disease . 15.5. METABOLOMICS. 15.6. FORENSIC MASS SPECTROMETRY. 15.6.1. Analysis of Banned Substances of Abuse. 15.6.2 Analysis of Explosives. 15.6.3. Analysis of Glass and Paints. 15.6.4. Authenticity of Questioned Documents. 15.6.5. Mass spectrometry in Bioterror Defense. 15.7. SCREENING COMBINATORIAL LIBRARIES. 15.7.1. Combinatorial Synthetic Procedures. 15.7.2. Screening Methods. 15.8. ADDITIONAL READING. 15.9. REFERENCES . Appendix A: Abbreviations. Appendix B: Physical Constants, Units, and Conversion Factors . Appendix C: Isotopes of Naturally Occurring Elements and their Abundances. Appendix D: Reference Ions and Their Exact Masses. Appendix E: Internet Resources. Appendix F. Answers and Hints to Exercises. Index.

O autorze

Chhabil Dass, PhD, is an Associate Professor in the Department of Chemistry at The University of Memphis. He is the author of Principles and Practice of Biological Mass Spectrometry (Wiley–Interscience).