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Mass Spectrometry in Drug Discovery
XI
trends in analytical chemistry, vol. 21, no. 6+7, 2002
book reviews Mass Spectrometry in Drug Discovery Mass Spectrometry in Drug Discovery, edited by David T. Rossi and Michael W. Sinz, Marcel Dekker, Inc., New York, USA, 2002, viii + 420 pages, $165.00, ISBN 0-82470607-2 PII: S0165-9936(02)00607-6
This book is somewhat more limited in scope than the title might imply. As the editors state in their Preface, the focus of the book is on the pervasive use of liquid chromatography/mass spectrometry (LC/MS) in the field of drug discovery. They are enthusiastic about this development, characterizing it as a revolutionary change, being second only to combinatorial chemistry in its effects on this field. As a consequence, the majority of the references to drug-discovery applications of mass spectrometry involve LC/MS interfaced via either atmospheric ionization (API) or electrospray ionization (ESI), which, for reasons that are not explained, is referred to as ESP throughout the book. Most of the chapters are written by authors employed by pharmaceutical companies, ensuring that the focus on drug-discovery issues is maintained. Part I includes two chapters by the editors, establishing the context for the rest of the book. Chapter 2 contains an interesting chart outlining the parallel development of LC/MS and pharmaceutical drug discovery over the last century. Next, Part II covers mass-spectrometry instrumentation, with a single chapter appropriately titled ‘‘A Mass Spectrometry Primer’’. Part III is devoted to experimental strategies
and includes a chapter on relevant ion chemistry and fragmentation, followed by chapters on the LC/MS experiment and sample preparation for the drug-discovery applications of interest. The remainder of this book, Part IV – Applications, contains seven chapters, including several on drug-discovery approaches with minimal mass-spectrometry content. Overall, this is a high-quality volume that will well serve the intended audience, which would appear to be primarily industrial scientists involved in drug discovery. There are a few minor points that can be criticized, ranging from the trivial mistake of using the word ‘‘effected’’ on p. 1, where ‘‘affected’’ is meant, to the use of ESP, rather than the accepted acronym, ESI, for electrospray ionization. Similarly, the need for definitions on p. 13 of ‘‘in cerebro’’ and ‘‘in silico’’ is questionable, as is the too narrow definition of ‘‘proteomics’’. Because the mass-spectrometry instrumentation chapter is likely to be the only introduction that many readers will have to mass spectrometry, it is critical that this chapter be accurate. Therefore, it is slightly disconcerting to see what is commonly called ‘‘resolving power’’ m/m defined as resolution (its inverse) in equation (1). Another minor error, which could be confusing, is the discussion headed ‘‘Magnetic Sector Mass Analyzers’’ (p. 47), where the author has apparently equated such instruments, which are low-resolution devices, to doublefocusing magnetic/electric sector instruments, which are the highperformance instruments described.
When the discussion moves on to MS/MS, the older ‘‘daughter ion’’ terminology is used, rather what has come to be the preferred term, ‘‘product ion’’, to describe such species. The brief discussion of ion cyclotron resonance (ICR) and Fourier transform mass analyzers (FTMS) is somewhat confused. Contrary to the description here, scanning ICR spectrometers generally operate at a fixed frequency and scan the magnetic field to produce a spectrum, rather that scanning the frequency at a fixed field. Also, the explanation of why a high vacuum is needed to obtain high mass resolution in FTMS is confusing and should have more simply stated that collisional damping of the signal (a function of pressure) is limiting. However, these are minor problems with a well-written chapter, which does a good job of getting the essential points across. Throughout, the chapters are well documented with references to the primary literature, mostly extending through the year 2000, for readers interested in consulting those sources for more detail. On the other hand, the five-page index is minimal. In summary, although a few errors appear, overall this is an excellent book, which does a good job of bringing together LC/MS developments and theory in a way that will serve well those involved in the field of drug discovery. Therefore, I can recommend ‘‘Mass Spectrometry in Drug Discovery’’ as an excellent introduction to this important topic. CHARLES L. WILKINS University of Arkansas, Fayetteville, Arkansas, 72701, USA.
trends in analytical chemistry, vol. 21, no. 6+7, 2002
book reviews Mass Spectrometry in Drug Discovery Mass Spectrometry in Drug Discovery, edited by David T. Rossi and Michael W. Sinz, Marcel Dekker, Inc., New York, USA, 2002, viii + 420 pages, $165.00, ISBN 0-82470607-2 PII: S0165-9936(02)00607-6
This book is somewhat more limited in scope than the title might imply. As the editors state in their Preface, the focus of the book is on the pervasive use of liquid chromatography/mass spectrometry (LC/MS) in the field of drug discovery. They are enthusiastic about this development, characterizing it as a revolutionary change, being second only to combinatorial chemistry in its effects on this field. As a consequence, the majority of the references to drug-discovery applications of mass spectrometry involve LC/MS interfaced via either atmospheric ionization (API) or electrospray ionization (ESI), which, for reasons that are not explained, is referred to as ESP throughout the book. Most of the chapters are written by authors employed by pharmaceutical companies, ensuring that the focus on drug-discovery issues is maintained. Part I includes two chapters by the editors, establishing the context for the rest of the book. Chapter 2 contains an interesting chart outlining the parallel development of LC/MS and pharmaceutical drug discovery over the last century. Next, Part II covers mass-spectrometry instrumentation, with a single chapter appropriately titled ‘‘A Mass Spectrometry Primer’’. Part III is devoted to experimental strategies
and includes a chapter on relevant ion chemistry and fragmentation, followed by chapters on the LC/MS experiment and sample preparation for the drug-discovery applications of interest. The remainder of this book, Part IV – Applications, contains seven chapters, including several on drug-discovery approaches with minimal mass-spectrometry content. Overall, this is a high-quality volume that will well serve the intended audience, which would appear to be primarily industrial scientists involved in drug discovery. There are a few minor points that can be criticized, ranging from the trivial mistake of using the word ‘‘effected’’ on p. 1, where ‘‘affected’’ is meant, to the use of ESP, rather than the accepted acronym, ESI, for electrospray ionization. Similarly, the need for definitions on p. 13 of ‘‘in cerebro’’ and ‘‘in silico’’ is questionable, as is the too narrow definition of ‘‘proteomics’’. Because the mass-spectrometry instrumentation chapter is likely to be the only introduction that many readers will have to mass spectrometry, it is critical that this chapter be accurate. Therefore, it is slightly disconcerting to see what is commonly called ‘‘resolving power’’ m/m defined as resolution (its inverse) in equation (1). Another minor error, which could be confusing, is the discussion headed ‘‘Magnetic Sector Mass Analyzers’’ (p. 47), where the author has apparently equated such instruments, which are low-resolution devices, to doublefocusing magnetic/electric sector instruments, which are the highperformance instruments described.
When the discussion moves on to MS/MS, the older ‘‘daughter ion’’ terminology is used, rather what has come to be the preferred term, ‘‘product ion’’, to describe such species. The brief discussion of ion cyclotron resonance (ICR) and Fourier transform mass analyzers (FTMS) is somewhat confused. Contrary to the description here, scanning ICR spectrometers generally operate at a fixed frequency and scan the magnetic field to produce a spectrum, rather that scanning the frequency at a fixed field. Also, the explanation of why a high vacuum is needed to obtain high mass resolution in FTMS is confusing and should have more simply stated that collisional damping of the signal (a function of pressure) is limiting. However, these are minor problems with a well-written chapter, which does a good job of getting the essential points across. Throughout, the chapters are well documented with references to the primary literature, mostly extending through the year 2000, for readers interested in consulting those sources for more detail. On the other hand, the five-page index is minimal. In summary, although a few errors appear, overall this is an excellent book, which does a good job of bringing together LC/MS developments and theory in a way that will serve well those involved in the field of drug discovery. Therefore, I can recommend ‘‘Mass Spectrometry in Drug Discovery’’ as an excellent introduction to this important topic. CHARLES L. WILKINS University of Arkansas, Fayetteville, Arkansas, 72701, USA.