Abstract
| I. | Introduction | 370 |
| II. | Techniques That Are Usually Employed in the Study of Bioorganic Macromolecules | 371 |
| | A. Proteins and Peptides | 371 |
| | B. Oligonucleotides | 374 |
| | C. Oligosaccharides and Glycoconjugates | 375 |
| | D. Various Complexes (DNA–Protein, Antigen–Antibody, Macromolecules–Metals) | 377 |
| III. | Common Problems and Developments in the Analysis of Bioorganic Macromolecules by Mass Spectrometry | 377 |
| | A. Ionization Source Problems and Developments | 377 |
| | 1. Sensitivity | 377 |
| | 2. Problems with Buffers | 379 |
| | 3. Multicharge Effect | 381 |
| | B. Mass Analyzer Problems and Developments | 381 |
| | 1. Linear Dynamic Range | 381 |
| | 2. Tandem Mass Spectrometry | 382 |
| | 3. Sensitivity | 382 |
| | 4. Resolution | 383 |
| | 5. Mass Accuracy | 383 |
| IV. | New Promising Technologies | 384 |
| | A. Interfaces and Ionization Sources | 384 |
| | 1. Improvements in the Coupling of Liquid‐Phase Separation Systems to Mass Spectrometry | 384 |
| | 2. AP‐MALDI | 384 |
| | 3. Deprotonant Agents | 385 |
| | 4. Sonic Spray Ionization | 388 |
| | 5. APCI without Corona Discharge | 391 |
| | B. Mass Analyzers | 393 |
| | 1. Linear Quadrupole Ion Trap | 394 |
| | 2. TOF Analyzers with New Detectors | 395 |
| | 3. Multiple Mass Analyzers | 396 |
| V. | Software for Data Treatment | 397 |
| VI. | Conclusions and Future Developments | 399 |
| Acknowledgments | | 400 |
| References | | 400 |
In recent years, mass spectrometry has been increasingly used for the analysis of various macromolecules of biological, biomedical, and biochemical interest. This increase has been made possible by two key developments: the advent of electrospray ionization (ESI) and matrix‐assisted laser desorption ionization (MALDI) sources. The two new techniques produce a significant increase in mass range and in sensitivity that led to the development of new applications and of new analyzer designs, software, and robotics. This review, apart from the description of the status of mass spectrometry in the analysis of bioorganic macromolecules, is mainly devoted to the illustration of the more recent promising techniques and on their possible future evolution. © 2003
Wiley Periodicals, Inc., Mass Spec Rev 22:369–406, 2003; Published online in Wiley InterScience (www.interscience.wiley.com). DOI 10.1002/mas.10062