The ionization process in mass spectrometry (MS) creates ions from neutral molecules or extracts preformed ions from the sample. Additionally, the ionization source must facilitate the efficient transport of ions into the mass analyzer of the instrument for mass analysis. In the nearly 100 years of MS, and in 75 years of MS as a method of instrumental analysis, a great breadth and variety of ionization methods have been developed. The applications of these methods reflect the nature of the sample molecule (its volatility and thermal stability), the complexity of its environment (solid, liquid, or gas, and whether it is a mixture or purified), and the requisite flux and persistence of the ions created from the sample. The final four ionization methods in modern MS are electron ionization (EI) and chemical ionization (CI) for volatile samples, and electrospray ionization (ESI) and matrix-assisted laser desorption–ionization (MALDI) for nonvolatile samples. Of the many other distinct ionization methods available (as contrasted with commercial variants of the final four), some are no longer used, a few remain useful in specialized research, and several are used in successful commercial implementations of modern MS. In this installment, we describe the basics of a few "less often seen" ionization methods.
In the last two installments of this column, we discussed the basics of models that relate the extent of dissociations of isolated ions to their internal energies. The validity of these models is tested by comparison of the predicted results with experimental measurements. For example, an ionization method could create a molecular ion with different amounts of known internal energy, and then the extent of dissociation to fragment ions could be assessed as a function of the internal energy.
Charge-Exchange IonizationOne method used to create molecular ions of known internal energy is charge-exchange ionization. Tedder and Vidaud (1) provide an overview of this method. The basic charge-exchange reaction is
X+ + M → X + M+ 
where X represents the ionizing agent and M represents the sample molecule to be ionized. In the collision between these two species, the charge is transferred from the agent X to the molecule M. The collision should be at a low relative kinetic energy so that none of the kinetic energy is transformed into internal energy of the ion M+. The center-of-mass collision energy is usually held to less than 10 eV. The ionization potential of X is known. If it exceeds the ionization potential of M, then M+ is created with an internal energy that equals the difference between the ionization potentials.
Charge-exchange ionization can be used to create mass spectra that resemble electron ionization (EI) mass spectra (2) when the source conditions preclude the usual EI process. The selectivity inherent in charge exchange can be used as an advantage when only certain components of a mixture should be ionized. In these applications, the agent X is chosen so that some components are ionized and others are not, and therefore no separation is necessary. Praun and Villinger (3) describe such an application in the analysis of exhaled breath. An off-line analysis is most often used, but the system is simple enough that it also could be used on-line, although the cost of this dedicated analysis would be high. Because no separation is necessary, analysis is rapid, even when 114 different volatile compounds (distinguished by their mass) were monitored (samples included acetaldehyde, acetone, acetonitrile, ammonia, benzene, ethanol, methane, acetic acid, isoprene, and compounds directly related to administered drugs). Why would one want to monitor so many different compounds? Individual organ function in humans has been linked to approximately 60 different compounds found in varying concentrations in exhaled breath (4,5). The comprehensive and quantitative analysis provided by charge-exchange mass spectrometry (MS) may be useful for diagnostic and evaluation purposes.