Mass Spectrometry/ Mass Spectrometry:

Techniques and Applications of Tandem

Mass Spectrometry

Kenneth L Busch Department of Chemistry, Indiana University, Bloomington, IN 47405

Gary L. Clish and Scott A. McLuckey Analytical Chemistry Division, Oak Ridge National Laboratory, Oak Ridge, TN 37831

VCH

Table of Contents

Acknowledgments v

Preface vii

1. Introduction to Mass Spectrometry/Mass Spectrometry 1 1.1. History of mass spectrometry/mass spectrometry 1 1.2. Concepts and principles 3 1.3. Nomenclature 12

2. MS/MS Instrumentation 15 2.1. Introduction 15 2.2. Principles of charged-particle analysis 16

2.2.1. Electric sectors 17 2.2.2. Magnetic sectors 17 2.2.3. Quadrupole mass filters 18 2.2.4. Time-of-fiight analysis 19 2.2.5. The Wien filter 19 2.2.6. Fourier transform-ion cyclotron resonance 20 2.2.7. Ion trap mass spectrometers 21

2.3. Sector-based MS/MS instruments 22 2.3.1. One-sector instruments 22 2.3.2. Two-sector MS/MS instruments 23 2.3.3. Three- and four-sector MS/MS instruments 30

2.4. Quadrupole instruments 34 2.5. Hybrid instruments 36 2.6. MS/MS with ion-trapping techniques 45

2.6.1. MS/MS with an FT-ICR 45 2.6.2. MS/MS with an ITMS 48

2.7. Reaction regions 50 2.7.1. Kiloelectron-volt ion kinetic energy reaction regions 50 2.7.2. Electron-volt ion energy reaction regions 51

3. Reactions in MS/MS 53 3.1, Introduction 53 3.2. Unimolecular dissociation 54

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3.3. Activation reactions 63 3.3.1. Collisional activation 64

3.3.1.1. Kinematics 66 3.3.1.2. Dynamics 70 3.3.1.3. Kiloelectron-volt collision energy collisional activation 75 3.3.1.4. Electron-volt collision energy collisional activation 78 3.3.1.5. Target gas effects 83

3.3.2. Photodissociation 86 3.3.3. Electron excitation 90 3.3.4. Surface-induced dissociation 93

3.4. Reactive collisions 95 3.5. Charge permutation reactions 99

3.5.1. Charge exchange reactions 99 3.5.1.1. m^+N->mp + N+- 99 3.5.1.2. m-'+N-*mp + N- 100 3.5.1.3. m]+ + N-+ m+

p'+ N+' 101 3.5.2. Collisional ionization reactions 102

3.5.2.1. mp-+N->mf+N+2e- 102 3.5.2.2. mp"+N-+mP

+ + N+e- 103 3.5.2.3. mp + N^m+'+N+e- 105

4. Applications of MS/MS to Fundamental Studies 107 4.1. Introduction 107 4.2. Ion structures 107

4.2.1. Unimolecular chemistry 108 4.2.1.1. Metastable ions 110 4.2.1.2. Activated ions 112

4.2.2. Bimolecular chemistry 120 4.2.3. Neutral structures 122

4.3. Reaction mechanisms 123 4.3.1. Unimolecular reactions in the ion source 124 4.3.2. Unimolecular reactions in reaction regions 126 4.3.3. Bimolecular reactions in the ion source 131 4.3.4. Bimolecular reactions in a reaction region 132

4.4. Thermochemistry 137 4.4.1. Energy gain/loss measurements 137 4.4.2. Kinetic energy release measurements 144 4.4.3. Relative product ion abundances 145

4.4.3.1. Thermochemical information from ion-bound dimers 145 4.4.3.2. Ion internal energies from ion abundances 149

5. Characteristics of MS/MS for Analytical Applications 153 5.1. Sample considerations 153

5.1.1. Sample collection 153 5.1.2. Sample contamination 155 5.1.3. Sample derivatization 155

5.2. Choice of ionization method 157 5.2.1. Review of ionization methods 157 5.2.2. Analytical requirements for sample ionization 159

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5.2.2.1. Molecular and ionic structural correspondence 159 5.2.2.2. Ionflux 160

5.2.3. Matrix effects 161 5.3. Interpretation of MS/MS spectra 162

5.3.1. High-energy MS/MS spectra 163 5.3.2. Low-energy MS/MS spectra 167 5.3.3. Automated Systems 169

Analytical Applications 173 6.1. Environmental applications 173

6.1.1. Priority pollutant analysis 174 6.1.2. Polyhalogenated Compounds 175 6.1.3. Atmospheric pollutants 178 6.1.4. Water pollutants 179 6.1.5. Indoor air pollution 179

6.2. Natural products applications 180 6.2.1. Alkaloids, lipids, and other naturally occurring Compounds 180 6.2.2. Toxic natural Compounds 187

6.3. Industrial products applications 191 6.3.1. Dyes 192 6.3.2. Surfactants 193 6.3.3. Polymers 194 6.3.4. Rubber and rubber additives 198 6.3.5. Agricultural products 199

6.4. Foods and flavors applications 199 6.4.1. Food components 201 6.4.2. Food additives 205

6.5. Forensic chemistry applications 206 6.6. Petroleum and petroleum products applications 209

6.6.1. Geochemical applications 210 6.6.2. Fuel characterization 212 6.6.3. Dating techniques with accelerator mass spectrometry 216

6.7. Bioorganic applications 216 6.7.1. Biological Compound classes 217

6.7.1.1. Carbohydrates and saccharides 217 6.7.1.2. Nucleosides and nucleotides 224 6.7.1.3. Fatty acids and lipids 232 6.7.1.4. Steroids 235 6.7.1.5. Bioamines 246 6.7.1.6. Peptides 248

6.8. Pharmaceutical applications 265 6.8.1. Drag assays and drug structures 266 6.8.2. Drug residues 270 6.8.3. Drag metabolites 273 6.8.4. Diagnosis and metabolic profiling 276

6.9. Applications to continuous flow samples and processes 277

Conclusions and Outlook 279 7.1. Instrumentation in MS/MS 279

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7.2. Outlook for advanced applications 280 7.3. Interpretation of MS/MS data 282 7.4. Conclusions 283

References 285

Appendix A: MS/MS Scan Modes on Various Instrument Configurations 311

Appendix B: Frequently Used Symbols and Acronyms 317

Index 321