Medical Applications of Mass Spectrometry (eBook)

Cover 1
Contents 4
List of Contributors 16
Preface 20
Part I: Motivation and Essentials 24
Chapter 1. Introduction 26
Chapter 2. Basics of analytical chemistry and mass spectrometry for medical professionals 30
1. Introduction 30
2. Terms and definitions 32
3. The analytical procedure 34
4. A case study: analysis of plasma sterol profile 37
5. Mass spectrometry 39
Reference 41
Chapter 3. Ethical, legal, safety, and scientific aspects of medical research 42
1. Ethical aspects 43
2. Legal aspects 45
3. Safety aspects 45
4. Handling biological materials 48
5. Clinical trials and protocols 51
6. Administrative procedures 56
References 57
Part II: Tools of the Trade 58
Chapter 4. Biomedical sampling 60
1. Sampling 60
2. Sample preparation 63
3. Extraction techniques 69
4. Automation and high throughput 80
5. Outlook 81
References 82
Chapter 5. Separation methods 84
1. Introduction 84
2. Gas chromatography 95
3. High-performance liquid chromatography 100
4. Electrophoretic techniques 108
5. Future trends 111
References 112
Chapter 6. Mass spectrometry instrumentation and techniques 116
1. Introduction 117
2. General questions about mass measurement and mass spectrometry 119
3. Separation techniques: gas chromatography (GC), and high-performance liquid chromatography (HPLC) 123
4. Ionization methods 125
5. Mass analyzers 142
6. Tandem mass spectrometry (MS/MS) 153
7. Selected terms for clarification 158
Acknowledgment 160
References 160
Chapter 7. Chemoinformatics„multivariate mathematical.statistical methods for data evaluation 164
1. Introduction 164
2. Data types and data pretreatment 166
3. Multivariate methods 169
4. Selected applications of chemometrics 185
Terms and terminology 187
References 189
Part III: Biomolecules 194
Chapter 8. Mass spectrometry in proteomics 196
1. Introduction 196
2. Methods in proteomics 199
3. Outlook 213
References 214
Chapter 9. De novo sequencing of peptides 218
Chapter 10. Protein bioinformatics 226
1. Highlights for medical professionals 226
2. Introduction 228
3. Methodology 229
4. Discussion 237
5. Future trends 238
6. Conclusions 242
Acknowledgments 243
References 243
Chapter 11. Analysis of complex lipidomes 246
1. Introduction 247
2. Methodology 249
3. Phospholipids 253
4. Acylglycerols 257
5. Sphingolipids 258
6. Sterols 260
7. Medical applications of MS-lipidomics 261
8. Future trends 263
9. Conclusions 263
References 263
Part IV: Selected Medical Applications 274
Chapter 12. Medical laboratory practice„possibilities for mass spectrometry 276
1. Introduction 276
2. Quality management 277
3. Inborn errors of metabolism 277
4. Assessment of in vivo metabolism using stable isotope techniques 281
5. Conclusions 282
References 282
Chapter 13. Therapeutic drug monitoring and measurement of drug concentrations using mass spectrometry 286
1. Introduction 286
2. Antiinfection drugs 290
3. Drugs acting on the central nervous system (CNS) 294
4. Cardiovascular drugs 296
5. Anticancer agents 299
6. Analgesics 303
7. Miscellaneous drug classes 306
References 308
Chapter 14. Mass spectrometry of infectious pathogens 314
1. Introduction 314
2. Methodology 318
3. Future trends and prospects 328
References 328
Chapter 15. Proteomics of viruses 332
1. Introduction 333
2. Virus–host interactions 340
3. Diagnostics 348
4. Discussion 354
5. Future trends 357
6. Conclusions 358
Acknowledgments 359
References 359
Chapter 16. Neonatal research 368
1. Introduction 369
2. Principle of the methodology 371
3. Quick reference for practical implementation of the methodology 372
4. Key points of the methodology 379
5. Ongoing extensions of NBS 389
6. Conclusions 397
Acknowledgments 399
References 399
Chapter 17. Applications of mass spectrometry in oncology 402
1. Introduction 403
2. New methodology„SELDI.TOF.MS 404
3. Other relevant methodological challenges 407
4. Diagnostic oncoproteomics based on SELDI–TOF–MS 409
5. Representative other applications 416
References 421
Chapter 18. Application of mass spectrometry in brain research: neurotransmitters, neuropeptides, and brain proteins 430
1. Introduction 430
2. Methodology 431
3. Discussion 440
4. Future trends 443
5. Conclusions 444
Acknowledgments 444
References 444
Chapter 19. The human pituitary proteome: clinical applications 448
1. Introduction 449
2. The pituitary gland and mass spectrometry: an endocrinologist’s perspective 453
3. Methodology 455
4. Discussion 469
5. Future trends 475
6. Conclusions 477
Acknowledgments 478
References 478
Chapter 20. Mass spectrometry of proteinous allergens inducing human diseases 482
1. Introduction 482
2. Methodology 488
3. Mass spectrometric identification of proteinous allergens 492
4. Future trends 500
5. Conclusions 502
References 503
Chapter 21. Mass spectrometry in clinical treatment 510
1. Introduction 510
2. Pediatrics 513
3. Oncology 516
References 522
Part V: Emerging Areas 526
Chapter 22. Biomarker discovery 528
1. Introduction 529
2. Biomarkers in medicine 531
3. Important definitions 532
4. Biomarkers discovery and complexity of biological systems 533
5. Biomarker discovery and omicsŽ 535
6. The biomarker discovery project 535
7. Challenges in the biomarker discovery pathway 539
8. Technical issues in experimental design 545
9. The discovery process overview 549
10. Conclusions 553
References 554
Chapter 23. Molecular imaging by mass spectrometry 556
1. Introduction 556
2. Methods 558
3. Discussion 570
4. Future trends 572
5. Conclusion 573
Acknowledgments 574
References 574
Chapter 24. Brief outlook 578
1. Trends in instrumentation 579
2. Emerging systems approach 581
3. Mass spectrometry in translational medicine 582
Index 584