Preface ........................................................ xi
Introduction .................................................... 1
Principles ................................................... 1
Diagram of a Mass Spectrometer ............................... 4
History ...................................................... 5
Ion Free Path ............................................... 10
1. Ion Sources ................................................. 15
1.1. Electron Ionization ................................... 15
1.2. Chemical Ionization ................................... 17
1.2.1. Proton transfer ............................... 19
1.2.2. Adduct formation .............................. 21
1.2.3. Charge-transfer chemical ionization ........... 21
1.2.4. Reagent gas ................................... 22
1.2.5. Negative ion formation ........................ 25
1.2.6. Desorption chemical ionization ................ 27
1.3. Field Ionization ...................................... 28
1.4. Fast Atom Bombardment and Liquid Secondary Ion Mass
Spectrometry .......................................... 29
1.5. Field Desorption ...................................... 31
1.6. Plasma Desorption ..................................... 32
1.7. Laser Desorption ...................................... 33
1.8. Matrix-Assisted Laser Desorption Ionization ........... 33
1.8.1. Principle of MALDI ............................ 33
1.8.2. Practical considerations ...................... 36
1.8.3. Fragmentations ................................ 39
1.8.4. Atmospheric pressure matrix-assisted laser
desorption ionization ......................... 39
1.9. Thermospray ........................................... 41
1.10. Atmospheric Pressure Ionization ....................... 42
1.11. Electrospray .......................................... 43
1.11.1. Multiply charged ions ......................... 46
1.11.2. Electrochemistry and electric field as
origins of multiply charged ions .............. 48
1.11.3. Sensitivity to concentration .................. 50
1.11.4. Limitation of ion current from the source by
the electrochemical process ................... 51
1.11.5. Practical considerations ...................... 54
1.12. Atmospheric Pressure Chemical Ionization .............. 55
1.13. Atmospheric Pressure Photoionization .................. 56
1.14. Atmospheric Pressure Secondary Ion Mass
Spectrometry .......................................... 61
1.14.1. Desorption electrospray ionization ............ 61
1.14.2. Direct analysis in real time .................. 62
1.15. Inorganic Ionization Sources .......................... 65
1.15.1. Thermal ionization source ..................... 65
1.15.2. Spark source .................................. 67
1.15.3. Glow discharge source ......................... 68
1.15.4. Inductively coupled plasma source ............. 69
1.15.5. Practical considerations ...................... 71
1.16. Gas-Phase Ion-Molecule Reactions ...................... 72
1.17. Formation and Fragmentation of Ions: Basic Rules ...... 76
1.17.1. Electron ionization and photoionization
under vacuum .................................. 77
1.17.2. Ionization at low pressure or at
atmospheric pressure .......................... 77
1.17.3. Proton transfer ............................... 77
1.17.4. Adduct formation .............................. 78
1.17.5. Formation of aggregates or clusters ........... 79
1.17.6. Reactions at the interface between source
and analyser .................................. 79
2. Mass Analysers .............................................. 85
2.1. Quadrupole Analysers .................................. 88
2.1.1. Description ................................... 88
2.1.2. Equations of motion ........................... 91
2.1.3. Ion guide and collision cell .................. 96
2.1.4. Spectrometers with several quadrupoles in
tandem ........................................ 98
2.2. Ion Trap Analysers ................................... 100
2.2.1. The 3D ion trap .............................. 100
2.2.2. The 2D ion trap .............................. 117
2.3. The Electrostatic Trap or 'Orbitrap' ................. 122
2.4. Time-of-Flight Analysers ............................. 126
2.4.1. Linear time-of-flight mass spectrometer ...... 126
2.4.2. Delayed pulsed extraction .................... 129
2.4.3. Reflectrons .................................. 131
2.4.4. Tandem mass spectrometry with time-of-
flight analyser .............................. 134
2.4.5. Orthogonal acceleration time-of-flight
instruments .................................. 139
2.5. Magnetic and Electromagnetic Analysers ............... 143
2.5.1. Action of the magnetic field ................. 143
2.5.2. Electrostatic field .......................... 144
2.5.3. Dispersion and resolution .................... 145
2.5.4. Practical considerations ..................... 146
2.5.5. Tandem mass spectrometry in electromagnetic
analysers .................................... 149
2.6. Ion Cyclotron Resonance and Fourier Transform Mass
Spectrometry ......................................... 157
2.6.1. General principle ............................ 157
2.6.2. Ion cyclotron resonance ...................... 159
2.6.3. Fourier transform mass spectrometry .......... 159
2.6.4. MSn in ICR/FTMS instruments .................. 164
2.7. Hybrid Instruments ................................... 164
2.7.1. Electromagnetic analysers coupled to
quadrupoles or ion trap ...................... 165
2.7.2. Ion trap analyser combined with time-of-
flight or ion cyclotron resonance ............ 166
2.7.3. Hybrids including time-of-flight with
orthogonal acceleration ...................... 167
3. Detectors and Computers ................................... 175
3.1. Detectors ............................................ 175
3.1.1. Photographic plate ........................... 176
3.1.2. Faraday cup .................................. 176
3.1.3. Electron multipliers ......................... 177
3.1.4. Electro-optical ion detectors ................ 181
3.2. Computers ............................................ 182
3.2.1. Functions .................................... 183
3.2.2. Instrumentation .............................. 183
3.2.3. Data acquisition ............................. 183
3.2.4. Data conversion .............................. 186
3.2.5. Data reduction ............................... 186
3.2.6. Library search ............................... 186
4. Tandem Mass Spectrometry ................................... 189
4.1. Tandem Mass Spectrometry in Space or in Time ......... 189
4.2. Tandem Mass Spectrometry Scan Modes .................. 192
4.3. Collision-Activated Decomposition or Collision-
Induced Dissociation ................................. 195
4.3.1. Collision energy conversion to internal
energy ....................................... 196
4.3.2. High-energy collision (keV) .................. 198
4.3.3. Low-energy collision (between 1 and
100 eV) ...................................... 199
4.4. Other Methods of Ion Activation ...................... 199
4.5. Reactions Studied in MS/MS ........................... 202
4.6. Tandem Mass Spectrometry Applications ................ 204
4.6.1. Structure elucidation ........................ 205
4.6.2. Selective detection of target compound
class ........................................ 207
4.6.3. Ion-molecule reaction ........................ 210
4.6.4. The kinetic method ........................... 211
5. Mass Spectrometry/Chromatography Coupling .................. 217
5.1. Elution Chromatography Coupling Techniques ........... 218
5.1.1. Gas chromatography/mass spectrometry ......... 219
5.1.2. Liquid chromatography/mass spectrometry ...... 221
5.1.3. Capillary electrophoresis/mass
spectrometry ................................. 228
5.2. Chromatography Data Acquisition Modes ................ 228
5.3. Data Recording and Treatment ......................... 230
5.3.1. Data recording ............................... 230
5.3.2. Instrument control and treatment of
results ...................................... 232
6. Analytical Information ..................................... 243
6.1. Mass Spectrometry Spectral Collections ............... 243
6.2. High Resolution ...................................... 245
6.2.1. Information at different resolving powers .... 249
6.2.2. Determination of the elemental composition ... 251
6.3. Isotopic Abundances .................................. 251
6.4. Low-mass Fragments and Lost Neutrals ................. 257
6.5. Number of Rings or Unsaturations ..................... 258
6.6. Mass and Electron Parities, Closed-shell Ions and
Open-shell Ions ...................................... 259
6.6.1. Electron parity .............................. 259
6.6.2. Mass parity .................................. 259
6.6.3. Relationship between mass and electron
parity ....................................... 260
6.7. Quantitative Data .................................... 260
6.7.1. Specificity .................................. 260
6.7.2. Sensitivity and detection limit .............. 262
6.7.3. External standard method ..................... 264
6.7.4. Sources of error ............................. 265
6.7.5. Internal standard method ..................... 266
6.7.6. Isotopic dilution method ..................... 268
7. Fragmentation Reactions .................................... 273
7.1. Electron Ionization and Fragmentation Rates .......... 273
7.2. Quasi-Equilibrium and RRKM Theory .................... 275
7.3. Ionization and Appearance Energies ................... 279
7.4. Fragmentation Reactions of Positive Ions ............. 280
7.4.1. Fragmentation of odd-electron cations
or radical cations (OE•+) .................... 280
7.4.2. Fragmentation of cations with an even
number of electrons (EE+) .................... 286
7.4.3. Fragmentations obeying the parity rule ....... 288
7.4.4. Fragmentations not obeying the parity rule ... 291
7.5. Fragmentation Reactions of Negative Ions ............. 291
7.5.1. Fragmentation mechanisms of even electron
anions (EE-) ................................. 292
7.5.2. Fragmentation mechanisms of radical
anions (OE•-) ................................ 293
7.6. Charge Remote Fragmentation .......................... 293
7.7. Spectrum Interpretation .............................. 294
7.7.1. Typical ions ................................. 296
7.7.2. Presence of the molecular ion ................ 296
7.7.3. Typical neutrals ............................. 296
7.7.4. A few examples of the interpretation of
mass spectra ................................. 298
8. Analysis of Biomolecules ................................... 305
8.1. Biomolecules and Mass Spectrometry ................... 305
8.2. Proteins and Peptides ................................ 306
8.2.1. ESIandMALDI .................................. 307
8.2.2. Structure and sequence determination using
fragmentation ................................ 309
8.2.3. Applications ................................. 324
8.3. Oligonucleotides ..................................... 342
8.3.1. Mass spectra of oligonucleotides ............. 343
8.3.2. Applications of mass spectrometry to
oligonucleotides ............................. 346
8.3.3. Fragmentation of oligonucleotides ............ 351
8.3.4. Characterization of modified
oligonucleotides ............................. 355
8.4. Oligosaccharides ..................................... 357
8.4.1. Mass spectra of oligosaccharides ............. 358
8.4.2. Fragmentation of oligosaccharides ............ 360
8.4.3. Degradation of oligosaccharides coupled
with mass spectrometry ....................... 367
8.5. Lipids ............................................... 371
8.5.1. Fatty acids .................................. 373
8.5.2. Acylglycerols ................................ 376
8.5.3. Bile acids ................................... 382
8.6. Metabolomics ......................................... 386
8.6.1. Mass spectrometry in metabolomics ............ 387
8.6.2. Applications ................................. 388
9. Exercises .................................................. 403
Questions .................................................. 403
Answers .................................................... 415
Appendices .................................................... 437
1. Nomenclature ........................................... 437
1.1. Units ............................................. 437
1.2. Definitions ....................................... 437
1.3. Analysers ......................................... 438
1.4. Detection ......................................... 439
1.5. Ionization ........................................ 440
1.6. Ion types ......................................... 441
1.7. Ion-molecule reaction ............................. 442
1.8. Fragmentation ..................................... 442
2. Acronyms and abbreviations ............................. 442
3. Fundamental Physical Constants ......................... 446
4A. Table of Isotopes in Ascending Mass Order .............. 447
4B. Table of Isotopes in Alphabetical Order ................ 452
5. Isotopic Abundances (in %) for Various Elemental
Compositions CHON ...................................... 457
6. Gas-Phase Ion Thermochemical Data of Molecules ......... 467
7. Gas-Phase Ion Thermochemical Data of Radicals .......... 469
8. Literature on Mass Spectrometry ........................ 470
9. Mass Spectrometry on Internet .......................... 476
Index ......................................................... 479
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