Tandem mass spectrometry techniques, generally

This section deals with some general principles of tandem mass spectrometry and its applicability to quantitative analysis. The MS/MS acronym is used in this book as a general term for aU tandem mass spectrometry techniques. More detailed descriptions of how the principles are exploited in practice for the various instrumental types are given in later sections of this chapter. The general concept of tandem mass spectrometry in qualitative (structural) analysis is that additional chemical information, over and above that contained in a conventional onedimensional mass spectrum, can be obtained by examining the connectivity relationships among some or all of the ions in that mass spectrum. The connectivities arise as a result of the dissociation reactions that lead to the fragment ions in a mass spectrum, e.g. ... 

Until 1981, mass spectrometry was limited, generally, to the analysis of volatile, relatively low-molecular-mass samples and was difficult to apply to nonvolatile peptides and proteins without first cutting them chemically into smaller volatile segments. During the past decade, the situation has changed radically with the advent of new ionization techniques and the development of tandem mass spectrometry. Now, the mass spectrometer has a well-deserved place in any laboratory interested in the analysis of peptides and proteins. 

A general overview of each of these steps is given below. This is followed by a specific example involving an increasingly powerful quantitation technique, liquid chromatography/tandem mass spectrometry (LC/MS/MS). 

If we consider only a few of the general requirements for the ideal polymer/additive analysis techniques (e.g. no matrix interferences, quantitative), then it is obvious that the choice is much restricted. Elements of the ideal method might include LD and MS, with reference to CRMs. Laser desorption and REMPI-MS are moving closest to direct selective sampling tandem mass spectrometry is supreme in identification. Direct-probe MS may yield accurate masses and concentrations of the components contained in the polymeric material. Selective sample preparation, efficient separation, selective detection, mass spectrometry and chemometric deconvolution techniques are complementary rather than competitive techniques. For elemental analysis, LA-ICP-ToFMS scores high. 

Tandem mass spectrometry H6,i46) both stationary 116> and flowing afterglow-methods 118,147) and drift tube techniques U6> have also been applied to some of the clustering reactions. Results for the gas-phase solvation of H+ by H2O and NH3 generally agree well with the values obtained by high pressure mass spectro-metric observations 148). 

Natural products and natural-like compounds, generally coming from microbes, plants, sponges and animals [2, 3] may be fully identified and quantified by means of modem and advanced analytical techniques, such as high-performance liquid chromatography (HPLC) coupled to various detectors - from the most common UV/Vis to mass spectrometry and tandem mass spectrometry (HPLC-MS and HPLC-MS/MS). The role of MS is to provide quantitative and qualitative information about mixtures separated by liquid chromatography [4],... 

In subsection 7.2.1, it was discussed that the neutral clusters generated from the beam source have a wide range of cluster sizes. Although there is no single, easily available technique which allows the size specific detection of neutral clusters, it is now well accepted that the cluster size distribution can be manipulated, to a certain extent, by careful control of the various experimental parameters. Mass spectrometric detection of clusters in general and tandem mass spectrometry in particular offer the inherent advantage of enabling size specific studies of the cluster ions. 

To benefit general readers, the discussion has been limited to methodologies that are accessible to nonspecialists and that can be carried out on commercially available spectrometers without special modifications. The chapter illustrates the principles of mass spectrometry by demonstrating how various techniques [MALDI, ESI, Fourier transform ion cyclotron resonance (FT-ICR), ion traps, and tandem mass spectrometry (MS-MS)] work. It also provides examples of utilizing mass spectrometry to solve biological and biochemical problems in the field of protein analysis, protein folding, and noncovalent interactions of protein-DNA complexes. 

Since 2000, a myriad of LC-MS techniques have been reported to detect an array of NMBAs. These methods are valuable because they are generally more sensitive and more practical because they can measure a number of NMBAs simultaneously. Likewise, pharmacokinetic studies of neuromuscular blockers require low detection limits (sensitive chromatographic techniques such as tandem mass spectrometry with electrospray ionization combined with liquid chromatographic separation (LC-ESI-MS-MS) are better suited for these types of clinical applications.Brief descriptions of representative LC-MS methods follow. 

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