电子书:《Applied Electrospray Mass Spectrometry》
History, Theory, and Instrumentation
Robert B. Cody
JEOL USA, Peabody, Massachusetts
In the last decade, electrospray ionization mass spectrometry (ESI–MS) has
become the most universally applied mass spectrometric technique for nonvolatile,
thermal-labile molecules ranging in size from small compounds
(300–1000 Da) to large biomolecules with molecular weights in excess of 150
kDa. Electrospray ionization emerged from the pioneering experiments of J.
Zeleny (1917) and later those of Malcolm Dole (late 1960s), who performed a
series of experiments defining the parameters required for introducing large
molecules as ions into the gas phase of a mass spectrometer. In 1984, John
Fenn and his coworker M. Yamashita in the United States and M. L.
Aleksandrov and his coworkers in the U.S.S.R. first reported the successful
coupling of ESI with quadrupole and magnetic sector mass analyzers, respectively.
Because ESI is relatively simple and works at atmospheric pressure, it
can be easily coupled to both high-performance liquid chromatography, allowing
the analysis of complex mixtures, and devices for automated sample analysis
— satisfying the quest among mass spectrometrists to provide an interface
to liquid separation methods. From the beginning, ESI showed signs that it
would become the primary MS tool in pharmaceutical and biomedical
research, especially in high-throughput screening of large chemical libraries,
impurity analysis, pharmacokinetics and metabolite identification, and protein
characterization.
This book brings together the work of contributors from academia and
industry who have played important roles in the continuing development of
this technique. Our goal is to present a compilation of the latest applications
of ESI to practitioners of mass spectrometry, as well as to other scientists interested
in applying this technique to their areas of research. The principal theme
of the book is mass spectrometric analysis in the areas of pharmaceutical, peptide,
and protein chemistry.
The book begins with a historical review of the ESI technique — its principles
and instrumentation (Chapter 1), followed by a description of nanospray
development and applications in macromolecules (Chapter 2). The remaining
chapters cover applications of small molecules (Chapters 3, 4, and 5), peptides/
proteins (Chapters 6, 7, and 8), noncovalent complexes (Chapter 9), special
topics in protein folding/unfolding (Chapter 10), and clinical/biomedical
applications (Chapter 11). Topics such as the structural elucidation of complex
natural products (Chapter 3), analysis of libraries of compounds prepared
using combinatorial chemistry (Chapter 4), and the application of ESI-MS in
the field of pharmacokinetics and drug metabolism studies (Chapter 5) are of
great importance to scientists in the pharmaceutical industries and are
described in great detail. Chapters 6, 7, and 8 explore the critical role of the
ESI technique in structural characterization of peptides/proteins, especially in
the rapidly evolving area of proteomics and in identifying gene-expressed proteins
in a high-throughput process (Chapter 8). Dynamic structures of proteins,
such as noncovalent interactions and folding/unfolding, are further covered in
Chapters 9 and 10. Finally, Chapter 11 deals with the application of microflow
ESI–MS in problems in the field of clinical and biomedical research.
We acknowledge the special efforts of all the authors, who have made
great contributions to this book. We also thank the Schering-Plough Research
Institute, Washington University, and the National Center for Research
Resources of the National Institutes of Health for their support. Special thanks
go to the acquisitions and production editors at Marcel Dekker, Inc., for their
assistance.
Birendra N. Pramanik
A. K. Ganguly
Michael L. Gross