Gas-Phase Ionization Techniques

Gas phase ionization techniques ionize the molecules that are in the gas phase. It is possible to bring molecules to the gas phase only of compounds that are volatile. To fulfil this requirement, a molecule must be nonpolar, not too big (molecular weight <1000 Da) and thermally stable, i.e. it must not decompose when heated. Although these are harsh... 

The most important gas phase ionization techniques are electron ionization and chemical ionization. The latter will be described in Section 2.6.2. 

APCI is a gas-phase ionization technique, which requires that a sample is completely evaporated before ionization can take place. Thus, APCI can be applied to samples that do not decompose upon heating during evaporation. 

Since most solvents used in reversed-phase LC have ionization energies above 10.0 eV, while many organic molecules of interest have an ionization energy below 10.0 eV, it is possible, in principle, to selectively ionize a sample. Atmospheric pressure photoionization (APPI) is a new technique first published in 2000, but has already been developed into a commercial product. APPI is a gas-phase ionization technique, which requires that a sample is completely evaporated before ionization can take place. Thus, APPI can be applied to samples that do not decompose upon heating during evaporation. 

The next gas-phase ionization technique for LC-MS is APPI. It is a relatively new method, and its strengths and weaknesses will become clear as the number of applications grows over time. Thus far APPI appears to work best at flow rates of 100-200 pi min At higher flow rates ionization efficiency is reduced. To increase sensitivity a dopant such as acetone, toluene, or anisole is introduced into the ionization region. First, the dopant is ionized by photons and next the dopant ions undergo ion-molecule reactions with ultimate ionization of the sample. Solvent components can have a major influence on the cascade of ion-molecule reactions, and should be selected with care. 

Electrospray ionization (ESI) is a soft ionization technique that accomplishes the transfer of ions from solution to the gas phase. The technique is extremely useful for the analysis of large, non-volatile, chargeable molecules such as proteins and nucleic acid polymers. [1] Different from fast atom bombardment (FAB, Chap. 9) the solution is composed of a volatile solvent and the ionic analyte at very low concentration, typically M. In addition, the transfer of ions... 

In atmospheric pressure chemical ionization (APCI) a similar interface to that used for ESI is used. A corona discharge is used to ionize the analyte in the atmospheric pressure region. The gas-phase ionization in APCI is more effective than ESI for analyzing less polar species. Both ESI and APCI are complementary methods that are well-suited for LC/MS techniques. 

Another procedure for sulfur isotope measurements has been developed where samples are converted to solid arsenic sulfide, AS0S3 (s), and measured by thermal ionization mass spectrometry (TIMS) (22). This technique offers several advantages over the gaseous methods in that both memory and isotope effects are eliminated, and the chemical procedure is simpler. A precision of 1 0/00, and the capability of making measurements on small samples, makes the TIMS technique competitive with gas phase MS techniques. 

At the opposite extreme of molecular size from DNA, small molecules and free atoms can be ionized and subjected to electrophoresis in the gas phase. The technique, named ion mobility spectroscopy (IMS) or plasma chromatography, would better be called gaseous electrophoresis for consistency. The uses and theory of this method can be found in the literature [31,32]. 

MS has been used for a number of years as a powerful tool for the study of drug biodeposition and metabolism [83-87]. These types of studies have traditionally been carried out by gas chromatography-MS techniques. However, the use of LC-MS has been growing, especially since the introduction of the thermospray interface. With the advent of liquid-phase ionization techniques, such as electrospray, it has become possible to use LC-MS for the structural characterization of highly polar molecules at very low concentrations. 

In the ion sources, the analysed samples are ionized prior to analysis in the mass spectrometer. A variety of ionization techniques are used for mass spectrometry. The most important considerations are the internal energy transferred during the ionization process and the physico-chemical properties of the analyte that can be ionized. Some ionization techniques are very energetic and cause extensive fragmentation. Other techniques are softer and only produce ions of the molecular species. Electron ionization, chemical ionization and field ionization are only suitable for gas-phase ionization and thus their use is limited to compounds sufficiently volatile and thermally stable. However, a large number of compounds are thermally labile or do not have sufficient vapour pressure. Molecules of these compounds must be directly extracted from the condensed to the gas phase. 

Field ionization (FI) is a method that uses very strong electric fields to produce ions from gas-phase molecules. Its use as a soft ionization method in organic mass spectrometry is principally due to Beckey [8], Like El or Cl, FI is only suitable for gas-phase ionization. Therefore, the sample is introduced into the FI source by the same techniques that are commonly used in El and Cl sources, for example using a direct probe that can be heated or the eluent from a gas chromatograph. 

Recently, there has been a surge in applying gas phase spectroscopic techniques for studies of biologically relevant species [1-9]. Laser desorption with supersonic cooling has fundamentally solved the problem of vaporization of non-volatile species [5, 7], Electrospray ionization coupled with ion trapping and cooling has... 

GC/MS analyses most often employ one of two complementary ionization processes, electron ionization (El) or chemical ionization (Cl). This is because both El and Cl are gas phase ionization phenomena and are therefore well suited to interface with a separation technique (GC) that is also accomplished in the gas phase. The extractables profiles shown in Figs. 3-5 along with the Abietic Acid GC/MS analysis shown in Fig. 1, were acquired using GC/MS with El. The El ionization process is based on the interaction of an energetic electron beam (70 eV) with neutral analyte molecules in the gas phase, producing a radical cation, or molecular ion (M+ ) that can undergo fragmentation in the gas phase after redistribution of excess... 

Mass Spectrometric Detection for SFC. The advantages of coupling a chromatographic technique with mass spectrometry are considerable, as evidenced by the major role of GC-MS in mixture analysis. However, in contrast to GC, where the effluent is compatible with classical gas phase ionization methods, the ideal approach to interfacing SFC or HFLC with mass spectrometry is not immediately obvious. 

Because of the advances in the gas-phase ionization of biomacromolecules, such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), mass spectrometry (MS) has become a powerful tool for detection, identification, and structural analysis of proteins, peptides, and polynucleotides. The molecules ionized in a gas phase by these methods are subsequently analyzed by sector, quadrupole, ion-trap, or time-of-flight mass spectrometers. In particular, the MS systems consisting of ESI and triple-stage quadrupole (ESI/TSQ) or ion-trap (IT) mass spectrometry and MALDI time-of-flight (MALDl/TOF) mass spectrometry have been most widely applied to the field of protein chemistry for the accurate determination of molecular mass of proteins and peptides, determination of amino acid sequence, identification of proteins by peptide mass databases, and analysis of posttranslational modifications such as phosphorylation and glycosylation. In general, current techniques allow detenni-... 

Soft ionization can be achieved in the gas phase, from the liquid phase, or from the solid phase. Gas-phase cationization techniques have been discussed in previous chapters, especially in Chaps. 5 and 6. Typical examples of liquid-phase ionization techniques are thermospray ionization (TSI) and electrospray ionization (ESI), which are especially important in combining liquid chromatography and mass spectrometry (LC-MS). A wide variety of solid-phase ionization or desorp-tion/ionization techniques have been developed over the years, including field... 

Sputtering by kilovolt ion beams produces far more neutral species than ions. When static methods are employed, one can assume that a large percentage of these sputtered neutrals will be intact molecules. Thus, there is the very real possibility for improving detection limits (sensitivity) if these neutrals can be observed by post-ionization in the gas phase. Such techniques are known as secondary neutral mass spectrometry (SNMS). ... 

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