Mass Spectrometry

Edmond de Hoffmann, Université Catholique de Louvain, Belgium & Ludwig Institute for Cancer Research, Brussels, Belgium.Vincent Stroobant, Ludwig Institute for Cancer Research, Brussels, Belgium.

• Preface xiIntroduction 1Principles 1Diagram of a Mass Spectrometer 4History 5             Ion Free Path 101 Ion Sources 151.1 Electron Ionization 151.2 Chemical Ionization 171.2.1 Proton transfer 191.2.2 Adduct formation 211.2.3 Charge-transfer chemical ionization 211.2.4 Reagent gas 221.2.5 Negative ion formation 251.2.6 Desorption chemical ionization 271.3 Field Ionization 281.4 Fast Atom Bombardment and Liquid Secondary Ion Mass Spectrometry 291.5 Field Desorption 311.6 Plasma Desorption 321.7 Laser Desorption 331.8 Matrix-Assisted Laser Desorption Ionization 331.8.1 Principle of MALDI 331.8.2 Practical considerations 361.8.3 Fragmentations 391.8.4 Atmospheric pressure matrix-assisted laser desorption ionization 391.9 Thermospray 411.10 Atmospheric Pressure Ionization 421.11 Electrospray 431.11.1 Multiply charged ions 461.11.2 Electrochemistry and electric field as origins of multiply charged ions 481.11.3 Sensitivity to concentration 501.11.4 Limitation of ion current from the source by the electrochemical process 511.11.5 Practical considerations 541.12 Atmospheric Pressure Chemical Ionization 551.13 Atmospheric Pressure Photoionization 561.14 Atmospheric Pressure Secondary Ion Mass Spectrometry 611.14.1 Desorption electrospray ionization 611.14.2 Direct analysis in real time 621.15 Inorganic Ionization Sources 651.15.1 Thermal ionization source 651.15.2 Spark source 671.15.3 Glow discharge source 681.15.4 Inductively coupled plasma source 691.15.5 Practical considerations 711.16 Gas-Phase Ion-Molecule Reactions 721.17 Formation and Fragmentation of Ions: Basic Rules 761.17.1 Electron ionization and photoionization under vacuum 771.17.2 Ionization at low pressure or at atmospheric pressure 771.17.3 Proton transfer 771.17.4 Adduct formation 781.17.5 Formation of aggregates or clusters 791.17.6 Reactions at the interface between source and analyser 792 Mass Analysers 852.1 Quadrupole Analysers 882.1.1 Description 882.1.2 Equations of motion 912.1.3 Ion guide and collision cell 962.1.4 Spectrometers with several quadrupoles in tandem 982.2 Ion Trap Analysers 1002.2.1 The 3D ion trap 1002.2.2 The 2D ion trap 1172.3 The Electrostatic Trap or ‘Orbitrap’ 1222.4 Time-of-Flight Analysers 1262.4.1 Linear time-of-flight mass spectrometer 1262.4.2 Delayed pulsed extraction 1292.4.3 Reflectrons 1312.4.4 Tandem mass spectrometry with time-of-flight analyser 1342.4.5 Orthogonal acceleration time-of-flight instruments 1392.5 Magnetic and Electromagnetic Analysers 1432.5.1 Action of the magnetic field 1432.5.2 Electrostatic field 1442.5.3 Dispersion and resolution 1452.5.4 Practical considerations 1462.5.5 Tandem mass spectrometry in electromagnetic analysers 1492.6 Ion Cyclotron Resonance and Fourier Transform Mass Spectrometry 1572.6.1 General principle 1572.6.2 Ion cyclotron resonance 1592.6.3 Fourier transform mass spectrometry 1592.6.4 MSn in ICR/FTMS instruments 1642.7 Hybrid Instruments 1642.7.1 Electromagnetic analysers coupled to quadrupoles or ion trap 1652.7.2 Ion trap analyser combined with time-of-flight or ion cyclotron resonance 1662.7.3 Hybrids including time-of-flight with orthogonal acceleration 1673 Detectors and Computers 1753.1 Detectors 1753.1.1 Photographic plate 1763.1.2 Faraday cup 1763.1.3 Electron multipliers 1773.1.4 Electro-optical ion detectors 1813.2 Computers 1823.2.1 Functions 1833.2.2 Instrumentation 1833.2.3 Data acquisition 1833.2.4 Data conversion 1863.2.5 Data reduction 1863.2.6 Library search 1864 Tandem Mass Spectrometry 1894.1 Tandem Mass Spectrometry in Space or in Time 1894.2 Tandem Mass Spectrometry Scan Modes 1924.3 Collision-Activated Decomposition or Collision-Induced Dissociation 1954.3.1 Collision energy conversion to internal energy 1964.3.2 High-energy collision (keV) 1984.3.3 Low-energy collision (between 1 and 100 eV) 1994.4 Other Methods of Ion Activation 1994.5 Reactions Studied in MS/MS 2024.6 Tandem Mass Spectrometry Applications 2044.6.1 Structure elucidation 2054.6.2 Selective detection of target compound class 2074.6.3 Ion–molecule reaction 2104.6.4 The kinetic method 2115 Mass Spectrometry/Chromatography Coupling 2175.1 Elution Chromatography Coupling Techniques 2185.1.1 Gas chromatography/mass spectrometry 2195.1.2 Liquid chromatography/mass spectrometry 2215.1.3 Capillary electrophoresis/mass spectrometry 2285.2 Chromatography Data Acquisition Modes 2285.3 Data Recording and Treatment 2305.3.1 Data recording 2305.3.2 Instrument control and treatment of results 2326 Analytical Information 2436.1 Mass Spectrometry Spectral Collections 2436.2 High Resolution 2456.2.1 Information at different resolving powers 2496.2.2 Determination of the elemental composition 2516.3 Isotopic Abundances 2516.4 Low-mass Fragments and Lost Neutrals 2576.5 Number of Rings or Unsaturations 2586.6 Mass and Electron Parities, Closed-shell Ions and Open-shell Ions 2596.6.1 Electron parity 2596.6.2 Mass parity 2596.6.3 Relationship between mass and electron parity 2606.7 Quantitative Data 2606.7.1 Specificity 2606.7.2 Sensitivity and detection limit 2626.7.3 External standard method 2646.7.4 Sources of error 2656.7.5 Internal standard method 2666.7.6 Isotopic dilution method 2687 Fragmentation Reactions 2737.1 Electron Ionization and Fragmentation Rates 2737.2 Quasi-Equilibrium and RRKM Theory 2757.3 Ionization and Appearance Energies 2797.4 Fragmentation Reactions of Positive Ions 2807.4.1 Fragmentation of odd-electron cations or radical cations (OE•+) 2807.4.2 Fragmentation of cations with an even number of electrons (EE+) 2867.4.3 Fragmentations obeying the parity rule 2887.4.4 Fragmentations not obeying the parity rule 2917.5 Fragmentation Reactions of Negative Ions 2917.5.1 Fragmentation mechanisms of even electron anions (EE–) 2927.5.2 Fragmentation mechanisms of radical anions (OE•−) 2937.6 Charge Remote Fragmentation 2937.7 Spectrum Interpretation 2947.7.1 Typical ions 2967.7.2 Presence of the molecular ion 2967.7.3 Typical neutrals 2967.7.4 A few examples of the interpretation of mass spectra 2988 Analysis of Biomolecules 3058.1 Biomolecules and Mass Spectrometry 3058.2 Proteins and Peptides 3068.2.1 ESI and MALDI 3078.2.2 Structure and sequence determination using fragmentation 3098.2.3 Applications 3248.3 Oligonucleotides 3428.3.1 Mass spectra of oligonucleotides 3438.3.2 Applications of mass spectrometry to oligonucleotides 3468.3.3 Fragmentation of oligonucleotides 3518.3.4 Characterization of modified oligonucleotides 3558.4 Oligosaccharides 3578.4.1 Mass spectra of oligosaccharides 3588.4.2 Fragmentation of oligosaccharides 3608.4.3 Degradation of oligosaccharides coupled with mass spectrometry 3678.5 Lipids 3718.5.1 Fatty acids 3738.5.2 Acylglycerols 3768.5.3 Bile acids 3828.6 Metabolomics 3868.6.1 Mass spectrometry in metabolomics 3878.6.2 Applications 3889 Exercises 403Questions 403Answers 415Appendices 4371 Nomenclature 4371.1 Units 4371.2 Definitions 4371.3 Analysers 4381.4 Detection 4391.5 Ionization 4401.6 Ion types 4411.7 Ion–molecule reaction 4421.8 Fragmentation 4422 Acronyms and abbreviations 4423 Fundamental Physical Constants 4464A Table of Isotopes in Ascending Mass Order 4474B Table of Isotopes in Alphabetical Order 4525 Isotopic Abundances (in %) for Various Elemental Compositions CHON 4576 Gas-Phase Ion Thermochemical Data of Molecules 4677 Gas-Phase Ion Thermochemical Data of Radicals 4698 Literature on Mass Spectrometry 4709 Mass Spectrometry on Internet 476Index 479

"This is a great book for everyone in the field to keep handy." (CHOICE, April 2008)  "Overview of the principles, theories, and key applications of modern mass spectrometry." (Materials and Corrosion, November 2007)