book review

Mass Spectrometry Books
Reviewed by: T.J. Nelson

Most advanced mass spectrometry books are collections of articles by various researchers. Typically, this means: repetition, spotty coverage of the subject, and considerable overlap with every other book on the subject. On the other hand, textbook-style books tend to be too elementary. A mass spec book that balances these two extremes is still waiting to be written.

Mass Spectrometry of Proteins and Peptides
(Methods in Molecular Biology Vol. 146)
John R. Chapman, ed.

C ontains detailed step-by-step protocols for beginning researchers on how to perform specific, narrowly-defined procedures. Although this collection of articles by various authors is over ten years old, most of the procedures are still useful. Even has a couple chapters on protein interactions.

Mass Spectrometry of Protein Interactions
Kevin M Downard, ed.

T his book is only 137 pages long, so when the authors drift away from the topic, as is understandable for a topic in which most of the existing methods don't work very well, it hurts. It has some useful information on how to use a mass spectrometer to analyze protein interactions, but a lot more useful information has been left out.

Principles and Practice of Biological Mass Spectrometry
Chhabil Dass

T his an introduction to the instrumentation and principles for analyzing proteins and other biomolecules by mass spectrometry. The first few chapters discuss and compare equipment and ionization methods, including MALDI TOF, ESI, tandem MS/MS, and FT-ICR (Fourier transform ion cyclotron resonance) mass spectrometry. The remainder of the book gives advice on sample treatment and a practical overview on the considerations for performing MS on phosphoproteins, glycoproteins, peptides, lipids, and oligonucleotides, and for analyzing non-covalent interactions. These sections review the literature of their respective fields, and give a clear understanding of what mass spectrometry can accomplish.

This book would be an invaluable starting point for someone interested in becoming familiar with mass spectrometry, or for chemists or biochemists who wish to obtain a broad overview of protein MS. The advantages and disadvantages of each type of spectrometer are clearly discussed, and the author tries to give an unbiased appraisal; however, he is clearly more familiar with ESI and MALDI than other types, such as magnetic sector or FT-ICR MS. There are few details on interpreting mass spectra, and no detailed protocols; the book concentrates on its task of painting the broad outlines of its subject, which it does very well.

However, the writing style is a bit dull, contains many careless mistakes and typos, and is confusing in places. For example, on page 249 the author says that fast atom bombardment (FAB) MS is practically useless for glycoproteins because glycopeptides rarely give a signal; but 5 pages later, after a detour through ESI and MALDI, the author returns to FAB and says that it is customary to derivatize glycopeptides before FAB-MS, and that FAB-MS analysis of glycoproteins provides a wealth of information, including compositions, heterogeneity, and oligosaccharide sequences. Figure 9.1, which illustrates the principal ion fragmentation patterns of peptides, is hopelessly screwed up, and the book contains a number of awkward sentences that require prior knowledge before their meaning can be disambiguated. Despite the many points of comparison of the different types of mass spectrometry throughout the book, it is not until page 289 that the author gets around to saying that MALDI is at least 10 times more sensitive than ESI. Nonetheless, the book is highly recommended to anyone interested in understanding mass spectrometers.

Interpreting Protein Mass Spectra
A. Peter Snyder
Oxford, 522 pp, hardcover, 2000

A lthough it starts out at a leisurely pace, Interpreting Protein Mass Spectra eventually gathers up enough courage to dive into its main topic: how to interpret protein mass spectra. The book is a clear and detailed exposition of interpreting mass fragmentation spectra of proteins, concentrating exclusively on patterns created by electrospray ionization (ESI). No detail of this incredibly boring but important subject is left to the imagination. The book contains numerous examples and exercises (even in the appendix), and has long chapters on interpretation of phosphoprotein spectra and glycoprotein spectra. Full of diagrams and illustrations.

LC/MS: A Practical User's Guide
Marvin C. McMaster

N ot everyone is in the situation of having a liquid chromatograph / mass spectrometer turn up in their lab. But if you do, there's a lot of basic stuff you need to learn fast. This short and vastly overpriced book, written by an LC/MS tech support guy, is designed to teach users rudimentary information they need to know before they're allowed to go near the mass spec. That way, they know precisely what part they're about to break. This is the book to read if you know nothing about HPLC or mass spectrometry, before you start on the operating manuals.

While there's some practical information in this book, it will be mostly review for anyone with any experience with HPLC or mass spec. The comments about HPLC are useful for those running 4.6-mm i.d. columns, but most people using mass spectrometry have probably switched to nano-LC and nanospray. Nanospray uses 50- or 75-micron silica capillaries, and doesn't require splitters which throw most of your sample away at the detector. Most of the suggestions in this book, like filtering your sample, simply won't work on these more modern systems, where your sample is often only a couple of microliters.

The discussion of mass spectrometers is fairly general and of limited use even for beginners. McMaster tends to drift into the uses of different types of mass spectrometry, and in so doing misses an opportunity to explain how to really maintain the mass spec. That would have made this a truly useful book.

The book also comes with a CD that contains a PowerPoint presentation.

Electrospray Ionization Mass Spectrometry
Fundamentals, Instrumentation & Applications
Richard B. Cole, ed.

T his collection of articles is divided into four equal sections: fundamental aspects of ESI, coupling of ESI to mass analyzers, coupling to LC&capillary electrophoresis, and applications. Covers droplet formation, fragmentation patterns of various types of biomolecules, and some specialized topics like nucleic acids and glycoconjugates. Too general for those with a practical problem, and too scattershot for those seeking in-depth knowledge, but a good way to get oriented to the capabilities of ESI.

Practical Aspects of Trapped Ion Mass Spectrometry
Vol. IV: Theory and Instrumentation
Raymond E. March, John F.J. Todd, eds.

T his book is a collection of articles describing, for the most part, design features of ion trap mass spectrometers. While the information is presented at a fairly sophisticated level, the title is somewhat misleading. The only chapter that is of practical use to experimenters is the one on glycoprotein fragmentation. The remainder is only “practical” if you're designing mass specs. If you are, then you have to have this book.

Quantitative Proteomics by Mass Spectrometry
(Methods in Molecular Biology Vol. 359)
Salvatore Sechi, ed.

T his book goes to the opposite extreme, giving practical and detailed step-by-step protocols for isotopic labeling of proteins for quantitative measurement. Short but useful if you just want to learn how to do it, and don't care how it works.

Proteome Research: Mass Spectrometry
Principles and Practice
Peter James, ed.

B asic procedures for identifying proteins by MALDI and microspray mass spectrometry. Unlike Quantitative Proteomics by Mass Spectrometry, this book is not a collection of protocols--it teaches the principles you need to know for routine analysis of proteins. About half the book is dedicated to the software (Sequest, homology searching, and databases). There are also chapters on identifying phosphoproteins and glycoproteins. Very good for anyone just starting out.

A Practical Guide to Instrumentation, Methods, and Applications
Franz Hillenkamp and Jasna Peter Katalinic, eds.

M ALDI (matrix-assisted laser desorption ionization) is a technique that uses laser ablation of a sample-coated target to vaporize molecules for injection into a mass spectrometer. The advantages of MALDI are its gentleness compared to electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), and the fact that MALDI produces mostly singly-charged ions. This means that fragile biomolecules such as proteins can produce a single peak without being fragmented.

Although MALDI can be used on ion traps, it's a bad match because of their limited mass range: ion traps can't detect ions with m/z above 2000 Da or so, while masses below 500 Da are not detectable because of saturation by MALDI matrix ions. MALDI is better suited for TOF mass spectrometers. However, most current-generation TOF machines have a limited dynamic range. They typically use only 8-bit A/D converters, which means that only 256 possible peak intensities are possible. Coupled with the inherent variability of laser desorption, signal suppression caused by other sample components, and the huge variabilities (up to 1000×) in the ionization efficiency of different molecules, this means that MALDI mass spectrometry is almost exclusively a qualitative tool, even when isotopic coding is used. As one author points out, no MALDI-MS protein profiling method has yet been validated for clinical studies. This is probably because of the great difficulty in obtaining reliable quantitative results with such machines. Even so, MALDI can be useful in molecule identification and structural studies, where accurate measurements aren't so important.

MALDI MS: A Practical Guide is a collection of nine comprehensive chapters, each written by a different expert in the field. It provides a good basic understanding of the technology for researchers contemplating the use of MALDI in their experiments. Chapters give overviews of the uses of MALDI for analyzing proteins, nucleic acids, glycans, lipids, small molecules, and synthetic polymers. The publication quality is excellent, with clear diagrams and color photos throughout. However, except in the chapter on nucleic acids, most of the authors are too optimistic about the usefulness of MALDI. Like mass spec salesmen, the authors give glowing descriptions of the benefits of MALDI MS while downplaying the many problems and disadvantages. Purchasing a MALDI-ion trap or even a MALDI-FT-ICR machine would be a big mistake for most protein laboratories, yet the reader would have to read carefully between the lines to recognize this.

Another problem with mass spectrometers, including those that use MALDI, is the low level of certainty of identification of biomolecules, especially in real-world biological samples, which may contain hundreds or thousands of other molecules, each accompanied by numerous fragmentation peaks. This is a particular problem for low-resolution instruments like ion traps. Unlike ESI, MALDI cannot be coupled to an LC to assist such overburdened machines in analyzing complex samples. Although this critical fact is mentioned, once again it's glossed over.

Another problem with this book is that specific instruments are only mentioned in passing. This may be understandable, considering that the current crop of instruments will probably be consigned to the scrap heap within a few years, but most readers would expect more specifics in a book with the phrase "practical guide to instrumentation" in the title. This is also not a methods book. Specific procedures for using or calibrating a MALDI mass spectrometer are not discussed. Special techniques, such as ion loss, post-source decay and mass spec imaging, are only mentioned in passing or in brief chapters. Therefore, this book won't be much help to someone already struggling to learn how to use a MALDI mass spectrometer. However, it gives a pretty good executive overview of the capabilities of MALDI for someone trying to decide whether MALDI is worth investing in. The only caveat is, you have to supply your own skepticism.

Handbook of GC/MS: Fundamentals and Applications, 2nd ed.
Hans-Joachim Hübshmann

G as chromatography/mass spectrometry (GC/MS) is the highest-resolution analytical system so far invented: up to 15,000 substances can be measured in a single sample using the latest GC×GC methods. Even UHPLC can't match this resolution. Combined with a high-resolution mass spectrometer, the power of such instruments to analyze volatile molecules is almost astronomical.

Handbook of GC/MS is an up-to-date (as of 2009) discussion of GC/MS. Unlike some other books, this one is not written by a roomful of random authors who are all talking about the same thing, but by a single authoritative expert. This book is similar to Gas Chromatography and Mass Spectrometry: A Practical Guide, which is due out in a new edition in early 2011, but gives more information on the equipment as well as a large section with detailed conditions for analyzing specific types of molecules. Thanks to the translation from German, the writing style is a little stiff, but readers with some background in GC, chromatography, or mass spec will learn a great deal about how to improve the performance of their instrument while bankrupting their institution at the same time. Does not cover ion mobility spectrometry or MRM (multiple reaction monitoring). The author has a pronounced bias toward Thermo.