Derivatization, in mass spectrometry

Zaikin VG, Halket JM. Derivatization in mass spectrometry—8. Soft ionization mass spectrometry of small molecules. Eur J Mass Spectrom 2006 12 79—115. 

Zalkin VG, HaUcet JM. Derivatization in mass spectrometry, 4. Formation of cyclic derivatives. Eur J Mass Spectrom 2004 10 555-68. 

Zaikin, V.G. Halket, J.M. Derivatization in Mass Spectrometry 4. Formation of Cyclic Derivatives. Eur. Mass Spectrom. 2004,10, 555-568. 

Anderegg, R.J. Derivatization in Mass Spectrometry Strategies for Controlling Fragmentation. Mass Spectrom. Rev. 1988, 7, 395-424. 

Halket, J.M. and Zaikin, V.G., Derivatization in mass spectrometry—5. Specific derivatization of monofunctional compounds. Eur. J. Mass Spectrom., 11, 127-160 (2005). 

Generally, the structure of fatty compounds offers two possibilities for performing derivatization reactions with the objective of improved fragmentation patterns in mass spectrometry. The first possibility is derivatization at the carboxylic acid moiety (C-1 remote-site derivatization ) the second possibility is derivatization of functional groups in the main fatty acid chain. Often both kinds of derivatization are carried out on one sample to facilitate analysis. 

This chapter has concentrated on only the major derivative classes employed in GC-MS, and only a few examples of each could be mentioned. However, the literature, including the other chapters of the present handbook, contains an abundance of references and descriptions of other derivative types, many of which will have hidden mass spectrometric potential for particular applications. Trace analyses have been covered in depth for steroids [202] and cannabinoids [203] and in the application of NICI to drugs [204] and neurotransmitters [205]. A recent volume [206] includes a number of specialist chapters devoted to the application of mass spectrometry in different areas of biomedical research. It can be consulted for more in-depth information of work done with particular analyte classes, and contains a short overview of chemical derivatization for mass spectrometry, including some GC-MS examples [207], Comprehensive reviews by Evershed, covering developments and new applications of GC-MS, contain many references to derivati-... 

One of the main, but not sole, purposes of derivatization is the transformation of non-volatile compounds into volatile derivatives. Each chromatographic method [GC, GC/ mass spectrometry (MS), high-performance liquid chromatography (HPLC), capillary electrophoresis (CE), etc.] being supplemented by derivatization of analytes permits us to solve some specific problems. The principal among them are summarized briefly in Table 1 more detailed comments follow. Some of the derivatization methods mentioned can also be used in mass spectrometry, which includes no preliminary chromatographic separation of analytes, but there are special derivatization techniques... 

The recent innovations in mass spectrometry involve methods for enhancing the vaporization, more accurately termed desorption, of relatively nonvolatile samples without derivatization. Even more significant are those advances that now allow for direct ionization of the sample to occur on the probe with subsequent desorption of the ions. As the efficiency of these new techniques improves, arguments begin to arise as to whether ionization of the sample components actually occurs prior to or subsequent to desorption (34, 35, 153, 154). Such arguments, however, need not concern us here. 

Liquid Ghromatography/Mass Spectrometry. Increased use of Hquid chromatography/mass spectrometry (Ic/ms) for stmctural identification and trace analysis has become apparent. Thermospray Ic/ms has been used to identify by-products in phenyl isocyanate precolumn derivatization reactions (74). Five compounds resulting from the reaction of phenyUsocyanate and the reaction medium were identified two from a reaction between phenyl isocyanate and methanol, two from the reaction between phenyl isocyanate and water, and one from the polymerisation of phenyl isocyanate. There were also two reports of derivatisation to enhance either the response or stmctural information from thermospray Ic/ms for linoleic acid hpoxygenase metabohtes (75) and for cortisol (76). 

The recent development and comparative application of modern separation techniques with regard to determination of alkylphosphonic acids and lewisite derivatives have been demonstrated. This report highlights advantages and shortcomings of GC equipped with mass spectrometry detector and HPLC as well as CE with UV-Vis detector. The comparison was made from the sampling point of view and separation/detection ability. The derivatization procedure for GC of main degradation products of nerve agents to determine in water samples was applied. Direct determination of lewisite derivatives by HPLC-UV was shown. Also optimization of indirect determination of alkylphosphonic acids in CE-UV was developed. Finally, the new instrumental development and future trends will be discussed. 

A large number of silylating agents exist for the introduction of the trimethylsilyl group onto a variety of alcohols. In general, the sterically least hindered alcohols are the most readily silylated, but are also the most labile to hydrolysis with either acid or base. Trimethylsilylation is used extensively for the derivatization of most functional groups to increase their volatility for gas chromatography and mass spectrometry. 

Figure 15.8 Multidimensional GC-MS separation of urinary acids after derivatization with methyl chloroformate (a) pre-column cliromatogram after splitless injection (h) Main-column selected ion monitoring cliromatogram (mass 84) of pyroglutamic acid methyl ester. Adapted from Journal of Chromatography, B 714, M. Heil et ai, Enantioselective multidimensional gas chromatography-mass spectrometry in the analysis of urinary organic acids , pp. 119-126, copyright 1998, with permission from Elsevier Science.

Maximum benefit from Gas Chromatography and Mass Spectrometry will be obtained if the user is aware of the information contained in the book. That is, Part I should be read to gain a practical understanding of GC/MS technology. In Part II, the reader will discover the nature of the material contained in each chapter. GC conditions for separating specific compounds are found under the appropriate chapter headings. The compounds for each GC separation are listed in order of elution, but more important, conditions that are likely to separate similar compound types are shown. Part II also contains information on derivatization, as well as on mass spectral interpretation for derivatized and underivatized compounds. Part III, combined with information from a library search, provides a list of ion masses and neutral losses for interpreting unknown compounds. The appendices in Part IV contain a wealth of information of value to the practice of GC and MS. 

Mizutani and coworkers57a confirmed the presence of polychloro(methylsulfonyl)biphenyls (159-170) as sulfur-containing metabolites of chlorobiphenyls (Cl-BP) in the feces of mice based on both GLC-mass spectrometry and chemical derivatization. In some cases comparison with authentic samples (161 and 162) was also made. When preparing 161 and 162,2,5-dichloro-3-(methylsulfonyl)aniline, 2,5-dichloro-l-iodo-3-(methylsulfonyl)benzene and 2,2, 5,5 -tetrachloro-3,3 -bis(methyl-sulfonyl)biphenyl were also obtained and their four peak El mass spectra reported572. Similar data were given for the corresponding 4-substituted intermediates, which were involved in the preparation of 162. Also 2,4, 5-trichloro-2 -(methylsulfonyl)-biphenyl was prepared and its four peak mass spectra given. Metabolites 163 and 164 were also identified by comparison with the authentic standards. 

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