A Mass Spectrometry Primer: Part I - - Chromatography Online
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A Mass Spectrometry Primer: Part I


LCGC North America




Technological changes affecting how we access information — both in the depth of knowledge we can access and the speed — leads to some observations about electronic versus print media. First, anything committed to public view must be of high scholarly order, often serving as a prime resource for equations and things we can't or won't remember. Second, once words have been printed, the value of the meaning they impart decreases as new understanding takes shape.

The electronic communication marvels still fall short of resolving all of the static shortcomings of print: increasingly ubiquitous blogs typically are narrowly focused, being written by a single individual, and the benefit of an interactive conversation developing deeper understanding is still on the horizon.

Therein lays the premise for this project. Primers in various forms can be found from a variety of authors and many of them are referenced for further reading in this one. What makes this one different is its continually self-validating existence residing on the web. Thousands of elite programmers at Google have developed uncanny heuristic algorithms to categorize and rate sites for quality. That is, searching for a mass spectrometry (MS)-related term will not turn up a site deemed "commercial" as a very high "hit."


Who Uses MS?
Readers of this column are familiar with the extent to which the editors go to ensure the technology is examined in an open "vendor neutral" fashion. The electronic primer, unfolding in print over the remainder of 2008, will reside on the Waters website and will be updated as readers' comments and suggestions come in either from readers in the U.S. and Europe or after visiting the Waters website (see "Resource Library," "Primers" at http://www.waters.com/).

This primer covers a wide range of topics related to modern MS practices and answers some frequently asked questions about the use and capabilities of mass spectrometers. Links also are provided to articles written for nonspecialists for more in-depth reading. The first section examines who uses mass spectrometers followed by how compounds are ionized in the source to be analyzed by mass spectrometers. A description of the various types of mass spectrometers is next and a discussion of the important topics of mass accuracy and resolution — or how well we can tell differences between closely related compounds. Chemistry, sample preparation, and data handling are considered, as well as the definition of some terms commonly in use in the most prevalent forms of MS practice today.

Before considering MS, you should consider the types of analyses you perform and the kind of results you expect from them:

  • Do you want to analyze large molecules, like proteins and peptides, or acquire small, aqueous-molecule data?
  • Do you look for target compounds at a determined level of detail, or do you want to characterize unknown samples?
  • Are your current separations robust, or must you develop methods from complex matrixes?
  • Do you require unit mass accuracy — say, 400 MW — or accuracy to 5?ppm, as in 400.0125 MW (or 2 mDa at mass 400)?
  • Do you process hundreds of samples a day? Thousands? Tens of thousands?

Who Uses MS?

Researchers and practitioners from various disciplines and subdisciplines within chemistry, biochemistry, and physics regularly depend upon MS analysis. Pharmaceutical industry workers involved in drug discovery and development rely on the specificity, dynamic range, and sensitivity of MS to differentiate closely related metabolites in a complex matrix and, thus, identify and quantify metabolites. Particularly in drug discovery, where compound identification and purity from synthesis and early pharmacokinetics are determined, MS has proved indispensable.


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