John M. Halket

This is the first of two reviews devoted to derivatization approaches for “soft” ionization mass spectrometry (fast atom bombardment, matrix assisted laser desorption/ionization, electrospray ionization and atmospheric pressure chemical ionization) and deals, in particular, with small molecules. The principles of the main “soft” ionization mass spectrometric methods as well as the reasons for derivatizing small molecules are briefly described. Derivatization methods for modification of amines, carboxylic acids, amino acids, alcohols, carbonyl compounds, monosaccharides, thiols, unsaturated and aromatic compounds etc. to improve their ionizability and to enhance structure information content are discussed. The use of “fixed”-charge bearing derivatization reagents is especially emphasized. Chemical aspects of derivatization and “soft” ionization mass spectrometric properties of derivatives are considered.

The review describes on-line derivatization/degradation methods employed in mass spectrometry to solve some structural and analytical problems. Advantages and applications of various positions of reaction systems connected mainly to a mass spectrometer or a gas chromatograph/mass spectrometer are considered. Among these are reaction systems connected directly to the mass spectrometer (reaction mass spectrometry, pyrolysis-mass spectrometry or direct pyrolysis-mass spectrometry); flash-heaters as reactors in gas chromatography/mass spectrometry (GC/MS); in-line chemical reactors located before the chromatographic column [pre-column derivatization/degradation with the use of catalytic reactions, pyrolysis (pyrolysis-GC/MS), degradation in elemental analyzers-isotope ratio mass pectrometry (EA-IRMS)]; on-column derivatization and deuteration; reactor located between the chromatographic column and a mass spectrometer [post-column catalytic derivatization, gas chromatograph-combustion-isotope ratio mass spectrometer (GC-c-IRMS)]. Post-column derivatization in high performance liquid chromatography/mass spectrometry is briefly mentioned. Application of such on-line methodology to structure elucidation of low molecular mass compounds and polymers, to the determination of isotope ratios of the most common elements, to the investigation of catalytic reactions is discussed.

The review describes chemical transformations of multi-functional compounds (amino acids and peptides, amino alcohols, amino thiols, hydroxy acids, oxo acids, oxo alcohols, compounds containing simultaneously three or more different groups etc.) by using step-wise or one-step modification or protection of functional groups. Some chemical aspects of mixed derivatization performed for improving the physical–chemical properties and mass spectral characteristics are discussed. Application of mixed derivatization to qualitative and quantitative analysis of various multifunctional compounds mainly in biological fluids and other matrices by gas chromatography/mass spectrometry in electron ionization, chemical ionization, negative-ion chemical ionization and selected ion monitoring modes is considered.

The present paper is complementary to the foregoing reviews and describes some additional methods of the derivatization of particular functional groups mainly to enhance the structural information content of electron ionization and chemical ionization mass spectra. Derivatization approaches for the modification of unsaturated compounds, alcoholic, carboxylic, carbonyl, amine and other functional groups, are discussed. Derivatization for separation and quantitative determination of chiral enantiomeric compounds is also considered. Preliminary chemical and physical–chemical degradation for structure elucidation of high molecular weight compounds (biopolymers, synthetic polymers) is mentioned. Chemical aspects of derivatizations and characteristic mass spectral features of derivatives are described briefly. Some particular applications of chemical modification, in conjunction with mass spectral measurements for the analysis of various important bioorganic compounds and compounds in biological fluids, air, environmental etc., are considered.

This fourth in a series of reviews describes a further common derivatization approach, namely, the formation of cyclic derivatives (cyclic acetals and ketals, boronates, siliconides, carbonates and other miscellaneous derivatives) that can be used to increase volatility and to improve chromatographic and, if possible, the mass spectral properties of various di- and polyfunctional compounds. Some chemical aspects of this type of derivatization are briefly discussed. Characteristic mass spectral features of various cyclic derivatives that are helpful in the structure determination, profiling and quantitation of multifunctional organic compounds are presented. Some recent analytical applications of mass spectrometry, in conjunction with preliminary cyclic derivative formation, are given.

The review is devoted to alkylation (arylation) as a widely employed derivatization procedure for the protection of OH (carboxylic acids, phosphoric acids, sulfonic acids, alcohols, polyols, phenols, enols), SH (thiols) and NH (amines, amides) groups in order to increase volatility, to improve the chromatographic properties and, if possible, mass spectral properties of derivatives. Chemical aspects of derivatization and various alkylation (arylation) reagents and reaction procedures are described. Specific mass spectral (electron ionization, chemical ionization) features of derivatives helpful in identification, structure elucidation, profiling and quantitative determination of the above-mentioned polar compounds by coupled gas chromatography or high-performance liquid chromatography are discussed. Some common analytical applications of the procedures in organic chemistry, clinical chemistry, environmental chemistry etc. are briefly summarized.

The present review is devoted to acylation as a widely employed derivatization procedure for protection of OH (alcohols, polyols, phenols, enols), SH (thiols) and NH (amines, amides) groups in order to increase volatility, improve chromatographic properties and, if possible, improve mass spectral properties of derivatives. Chemical aspects of derivatization and various acylating agents are characterized. Mass spectral [electron ionization (EI), chemical ionization (CI) and negative-ion (NI) CI] properties of derivatives that are helpful in identification, structure elucidation and quantitative determination of the analyzed compounds are discussed. Some recent analytical applications of the procedure in synthetic organic chemistry, clinical chemistry, environmental chemistry etc. are summarized.

This is the first of a series of reviews on the application of derivatization in mass spectrometry. A description is given of advances in silylation as a powerful tool used for increasing the volatility, thermal and thermo-catalytic stability, and chromatographic mobility of polar and unstable organic compounds. In addition to chemical aspects of silylation, mass spectral properties of silyl derivatives useful for structure determination and quantitation of various organic and biologically-active compounds, mainly by GC/MS, are described. Practically all tested and widely used silylating agents are described. The role of comprehensive libraries containing reference mass spectra for various silyl derivatives and search systems in structure determination is emphasized. Applications of silylation for particular analyses are summarised.