Mass Spectrometry Principles and Applications

502 Pages·2007·10.18 MB·English

JWBK172-FM JWBK172-Hoffmann August17,2007 15:26
Mass Spectrometry
Third Edition
i
JWBK172-FM JWBK172-Hoffmann August17,2007 15:26
ii
JWBK172-FM JWBK172-Hoffmann August17,2007 15:26
Mass Spectrometry
Principles and Applications
Third Edition
Edmond de Hoffmann
Universite´ Catholique de Louvain, Belgium & Ludwig Institute for
Cancer Research, Brussels, Belgium
Vincent Stroobant
Ludwig Institute for Cancer Research, Brussels, Belgium
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JWBK172-FM JWBK172-Hoffmann August17,2007 15:26
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LibraryofCongressCataloging-in-PublicationData
Hoffmann,Edmondde.
[Spectrome´triedemasse.English]
Massspectrometry:principlesandapplications.–3rded./EdmonddeHoffmann,VincentStroobant.
p.cm.
Includesbibliographicalreferencesandindex.
ISBN978-0-470-03310-4
1.Massspectrometry. I.Stroobant,Vincent. II.Title.
QD96.M3 H6413 2007
573(cid:3).65—dc22
2007021691
BritishLibraryCataloguinginPublicationData
AcataloguerecordforthisbookisavailablefromtheBritishLibrary
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iv
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Contents
Preface xi
Introduction 1
Principles 1
DiagramofaMassSpectrometer 4
History 5
IonFreePath 10
1 Ion Sources 15
1.1 ElectronIonization 15
1.2 ChemicalIonization 17
1.2.1 Protontransfer 19
1.2.2 Adductformation 21
1.2.3 Charge-transferchemicalionization 21
1.2.4 Reagentgas 22
1.2.5 Negativeionformation 25
1.2.6 Desorptionchemicalionization 27
1.3 FieldIonization 28
1.4 FastAtomBombardmentandLiquidSecondaryIonMassSpectrometry 29
1.5 FieldDesorption 31
1.6 PlasmaDesorption 32
1.7 LaserDesorption 33
1.8 Matrix-AssistedLaserDesorptionIonization 33
1.8.1 PrincipleofMALDI 33
1.8.2 Practicalconsiderations 36
1.8.3 Fragmentations 39
1.8.4 Atmosphericpressurematrix-assistedlaserdesorptionionization 39
1.9 Thermospray 41
1.10 AtmosphericPressureIonization 42
1.11 Electrospray 43
1.11.1 Multiplychargedions 46
1.11.2 Electrochemistryandelectricfieldasoriginsofmultiplychargedions 48
1.11.3 Sensitivitytoconcentration 50
1.11.4 Limitationofioncurrentfromthesourcebytheelectrochemicalprocess 51
1.11.5 Practicalconsiderations 54
1.12 AtmosphericPressureChemicalIonization 55
1.13 AtmosphericPressurePhotoionization 56
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vi CONTENTS
1.14 AtmosphericPressureSecondaryIonMassSpectrometry 61
1.14.1 Desorptionelectrosprayionization 61
1.14.2 Directanalysisinrealtime 62
1.15 InorganicIonizationSources 65
1.15.1 Thermalionizationsource 65
1.15.2 Sparksource 67
1.15.3 Glowdischargesource 68
1.15.4 Inductivelycoupledplasmasource 69
1.15.5 Practicalconsiderations 71
1.16 Gas-PhaseIon-MoleculeReactions 72
1.17 FormationandFragmentationofIons:BasicRules 76
1.17.1 Electronionizationandphotoionizationundervacuum 77
1.17.2 Ionizationatlowpressureoratatmosphericpressure 77
1.17.3 Protontransfer 77
1.17.4 Adductformation 78
1.17.5 Formationofaggregatesorclusters 79
1.17.6 Reactionsattheinterfacebetweensourceandanalyser 79
2 Mass Analysers 85
2.1 QuadrupoleAnalysers 88
2.1.1 Description 88
2.1.2 Equationsofmotion 91
2.1.3 Ionguideandcollisioncell 96
2.1.4 Spectrometerswithseveralquadrupolesintandem 98
2.2 IonTrapAnalysers 100
2.2.1 The3Diontrap 100
2.2.2 The2Diontrap 117
2.3 TheElectrostaticTrapor‘Orbitrap’ 122
2.4 Time-of-FlightAnalysers 126
2.4.1 Lineartime-of-flightmassspectrometer 126
2.4.2 Delayedpulsedextraction 129
2.4.3 Reflectrons 131
2.4.4 Tandemmassspectrometrywithtime-of-flightanalyser 134
2.4.5 Orthogonalaccelerationtime-of-flightinstruments 139
2.5 MagneticandElectromagneticAnalysers 143
2.5.1 Actionofthemagneticfield 143
2.5.2 Electrostaticfield 144
2.5.3 Dispersionandresolution 145
2.5.4 Practicalconsiderations 146
2.5.5 Tandemmassspectrometryinelectromagneticanalysers 149
2.6 IonCyclotronResonanceandFourierTransformMassSpectrometry 157
2.6.1 Generalprinciple 157
2.6.2 Ioncyclotronresonance 159
2.6.3 Fouriertransformmassspectrometry 159
2.6.4 MSn inICR/FTMSinstruments 164
2.7 HybridInstruments 164
2.7.1 Electromagneticanalyserscoupledtoquadrupolesoriontrap 165
2.7.2 Iontrapanalysercombinedwithtime-of-flightorioncyclotron
resonance 166
2.7.3 Hybridsincludingtime-of-flightwithorthogonalacceleration 167
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CONTENTS vii
3 Detectors and Computers 175
3.1 Detectors 175
3.1.1 Photographicplate 176
3.1.2 Faradaycup 176
3.1.3 Electronmultipliers 177
3.1.4 Electro-opticaliondetectors 181
3.2 Computers 182
3.2.1 Functions 183
3.2.2 Instrumentation 183
3.2.3 Dataacquisition 183
3.2.4 Dataconversion 186
3.2.5 Datareduction 186
3.2.6 Librarysearch 186
4 Tandem Mass Spectrometry 189
4.1 TandemMassSpectrometryinSpaceorinTime 189
4.2 TandemMassSpectrometryScanModes 192
4.3 Collision-ActivatedDecompositionorCollision-InducedDissociation 195
4.3.1 Collisionenergyconversiontointernalenergy 196
4.3.2 High-energycollision(keV) 198
4.3.3 Low-energycollision(between1and100eV) 199
4.4 OtherMethodsofIonActivation 199
4.5 ReactionsStudiedinMS/MS 202
4.6 TandemMassSpectrometryApplications 204
4.6.1 Structureelucidation 205
4.6.2 Selectivedetectionoftargetcompoundclass 207
4.6.3 Ion–moleculereaction 210
4.6.4 Thekineticmethod 211
5 Mass Spectrometry/Chromatography Coupling 217
5.1 ElutionChromatographyCouplingTechniques 218
5.1.1 Gaschromatography/massspectrometry 219
5.1.2 Liquidchromatography/massspectrometry 221
5.1.3 Capillaryelectrophoresis/massspectrometry 228
5.2 ChromatographyDataAcquisitionModes 228
5.3 DataRecordingandTreatment 230
5.3.1 Datarecording 230
5.3.2 Instrumentcontrolandtreatmentofresults 232
6 Analytical Information 243
6.1 MassSpectrometrySpectralCollections 243
6.2 HighResolution 245
6.2.1 Informationatdifferentresolvingpowers 249
6.2.2 Determinationoftheelementalcomposition 251
6.3 IsotopicAbundances 251
6.4 Low-massFragmentsandLostNeutrals 257
6.5 NumberofRingsorUnsaturations 258
6.6 MassandElectronParities,Closed-shellIonsandOpen-shellIons 259
6.6.1 Electronparity 259
6.6.2 Massparity 259
6.6.3 Relationshipbetweenmassandelectronparity 260
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viii CONTENTS
6.7 QuantitativeData 260
6.7.1 Specificity 260
6.7.2 Sensitivityanddetectionlimit 262
6.7.3 Externalstandardmethod 264
6.7.4 Sourcesoferror 265
6.7.5 Internalstandardmethod 266
6.7.6 Isotopicdilutionmethod 268
7 Fragmentation Reactions 273
7.1 ElectronIonizationandFragmentationRates 273
7.2 Quasi-EquilibriumandRRKMTheory 275
7.3 IonizationandAppearanceEnergies 279
7.4 FragmentationReactionsofPositiveIons 280
7.4.1 Fragmentationofodd-electroncationsorradicalcations(OE•+) 280
7.4.2 Fragmentationofcationswithanevennumberofelectrons(EE+) 286
7.4.3 Fragmentationsobeyingtheparityrule 288
7.4.4 Fragmentationsnotobeyingtheparityrule 291
7.5 FragmentationReactionsofNegativeIons 291
7.5.1 Fragmentationmechanismsofevenelectronanions(EE–) 292
7.5.2 Fragmentationmechanismsofradicalanions(OE•−) 293
7.6 ChargeRemoteFragmentation 293
7.7 SpectrumInterpretation 294
7.7.1 Typicalions 296
7.7.2 Presenceofthemolecularion 296
7.7.3 Typicalneutrals 296
7.7.4 Afewexamplesoftheinterpretationofmassspectra 298
8 Analysis of Biomolecules 305
8.1 BiomoleculesandMassSpectrometry 305
8.2 ProteinsandPeptides 306
8.2.1 ESIandMALDI 307
8.2.2 Structureandsequencedeterminationusingfragmentation 309
8.2.3 Applications 324
8.3 Oligonucleotides 342
8.3.1 Massspectraofoligonucleotides 343
8.3.2 Applicationsofmassspectrometrytooligonucleotides 346
8.3.3 Fragmentationofoligonucleotides 351
8.3.4 Characterizationofmodifiedoligonucleotides 355
8.4 Oligosaccharides 357
8.4.1 Massspectraofoligosaccharides 358
8.4.2 Fragmentationofoligosaccharides 360
8.4.3 Degradationofoligosaccharidescoupledwithmassspectrometry 367
8.5 Lipids 371
8.5.1 Fattyacids 373
8.5.2 Acylglycerols 376
8.5.3 Bileacids 382
8.6 Metabolomics 386
8.6.1 Massspectrometryinmetabolomics 387
8.6.2 Applications 388
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CONTENTS ix
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 Iontypes 441
1.7 Ion–moleculereaction 442
1.8 Fragmentation 442
2 Acronymsandabbreviations 442
3 FundamentalPhysicalConstants 446
4A TableofIsotopesinAscendingMassOrder 447
4B TableofIsotopesinAlphabeticalOrder 452
5 IsotopicAbundances(in%)forVariousElementalCompositionsCHON 457
6 Gas-PhaseIonThermochemicalDataofMolecules 467
7 Gas-PhaseIonThermochemicalDataofRadicals 469
8 LiteratureonMassSpectrometry 470
9 MassSpectrometryonInternet 476
Index 479