Analyte mass spectrometry

Budde, W.L., Analytical Mass Spectrometry Strategies for Environmental and Related Applications, American Chemical Society, Washington, D.C., 2001. 

For many years, electron ionization, then more usually known as electron impact, was the only ionization method used in analytical mass spectrometry and the spectra encountered showed exclusively the positively charged species produced during this process. Electron ionization also produces negatively charged ions although these are not usually of interest as they have almost no structural significance. Other ionization techniques, such as Cl, FAB, thermospray, electrospray and APCI, however, can be made to yield negative ions which are of analytical utility. 

The first systematic measurements of the reactions of ions with molecules in the gas phase were initiated largely by workers associated with analytical mass spectrometry.4-6 It was the rapidly expanding area of ion-molecule reactions which led to the origin of Gas-Phase Ion Chemistry as a distinct field.7 The discovery that ion-molecule equilibria in the gas phase can be determined by mass spectrometric techniques8 led to an explosion of thermochemical measurements based on determination of equilibria by a variety of techniques.9 Significantly, for the first time, information could be obtained on the thermochemistry of reactions which had solution counterparts of paramount importance such as acidities and basicities. These were obtained from proton transfer equilibria such as,... 

We have discussed above some of the applications of gas-phase ion thermochemical data to ionic reactions in solution. However the new analytical ion-transfer from solution to the gas-phase techniques have also created an application for these data in the new analytical mass spectrometry. In fact, much of the background knowledge required for this new analytical mass spectrometry, and particularly MALDI and electrospray, is the gas-phase ion chemistry developed for applications... 

The extension of analytical mass spectrometry from electron ionization (El) to chemical ionization (Cl) and then to the ion desorption (probably more correctly ion desolvation ) techniques terminating with ES, represents not only an increase of analytical capabilities, but also a broadening of the chemical horizon for the analytical mass spectrometrist. While Cl introduced the necessity for understanding ion—molecule reactions, such as proton transfer and acidities and basicities, the desolvation techniques bring the mass spectrometrist in touch with ions in solution, ion-ligand complexes, and intermediate states of ion solvation in the gas phase. Gas-phase ion chemistry can play a key role in this new interdisciplinary integration. 

J.J. Boon, and T. Learner, Analytical Mass Spectrometry of Artists Acrylic Emulsion Paints by Direct Temperature Resolved Mass Spectrometry and Laser Desorption Ionisation Mass Spectrometry, J. Anal. Appl. Pyrol., 64, 327 344 (2002). 

Crawford, L. R., Morrison, J. D. Anal. Chem. 40, 1968, 1469-1474. Computer methods in analytical mass spectrometry. Empirical identification of molecular class. 

From its very beginnings to the present almost any physical principle ranging from time-of-flight to cyclotron motion has been employed to construct mass-analyzing devices (Fig 4.1). Some of them became extremely successful at the time they were invented, for others it took decades until their potential had fully been recognized. The basic types of mass analyzers employed for analytical mass spectrometry are summarized below (Tab. 4.1). 

Guilhaus, M. The Return of Time-of-Flight to Analytical Mass Spectrometry. Adv. Mass Spectrom. 1995,13, 213-226. 

Nonetheless, during the first decades of analytical mass spectrometry low energy El spectra have been the only way to minimize fragmentation, and thereby to increase the relative intensity of a weak molecular ion peak. Nowadays, El mass spectra are preferably complemented with spectra obtained from so-called soft ionization methods (Chaps. 7-11). 

Koontz, S.L. Denton, M.B. A Very High Yield Electron Impact Ion Source for Analytical Mass Spectrometry. Int. J. Mass Spectrom. Ion Phys. 1981, 57, 227-239. 

Budde, W.L. Analytical Mass Spectrometry ACS and Oxford University Press Washington, D.C. and Oxford, 2001. Current Practice of Liquid Chromatography-Mass Spectrometry Niessen,... 

FAB and PD have been replaced by electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI) in the analytical mass spectrometry laboratory, because both of these newer techniques have a wider mass range of analysis and have lower detection limits. ESI and MALDI have become invaluable ionization techniques for nonvolatile components. This is particularly true for a wide range of biological molecules including proteins, peptides, nucleic acids, etc. Samples can be analyzed by ESI using either direct injection or introduction through liquid chromatography. 

Although well designed LC-MS/MS assays generally outperform immunoassays due to their accuracy, sensitivity, precision, and inherent multiplexing capability, they are not free from analytical problems. Besides limitations in selectivity— isobaric analytes cannot be distinguished—sudden and unpredictable ion yield attenuations, often known as ion suppression effect, have to be considered the Achilles heel of quantitative bio-analytical mass spectrometry. Ion yield attenuation is compromising both the accuracy of an assay and its precision. It can easily lead to gross errors in analyte quantification. 

Expansion in the field of analytical mass spectrometry has taken place in recent years in particular, the applicability of TLC-MS in the field of chemical and biochemical science has been significantly broadened. This technique can now be used for the analysis of macromolecules such as peptides, proteins, oligosaccharides, and oligonucleotides, etc. (Refer to Fig. 2.)... 

The electron-impact source is the work horse of analytical mass spectrometry. It is efficient, durable, and capable of producing a steady, intense beam of positive ions. Like all instruments, it must be periodically disassembled and cleaned, in addition to being equipped with a new filament. However, a well cared-for source may operate for 6 months or more. 

Budde W. L., Analytical mass spectrometry of herbicides. Mass. Spectrom. Rev., 23(1), 1-24, 2004. 

The 1970s and 1980s saw the advent of several new "soft" desorption/ ionization methods, many of which are now well-established in analytical mass spectrometry. The term "desorption/ionization" refers to a method in which the desorption (vaporization) and ionization steps occur essentially simultaneously. MALDI and several other techniques listed in Table 1 have important applications in polymer analysis. 

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