Chemical ionization and APCI
Chemical ionization (CI)   is a complementary method of electron ionization (IE). Since the ion source electron ionization is too energetic, causing too much fragmentation of molecular ions, therefore, the information of the molecular weight may be missing. The basic principle of chemical ionization is to ionize neutral molecules (methane, butane, ammonia …) by electron impact ionization. Once the molecules are ionized, they exchange the charge with the analytes. In this way, the analytes are protected from the electron beam, so chemical ionization is a gentle method compared to the electron ionization. CI ion sources are very similar to IE source, in fact, modern ion sources are built by combining EI/CI and can switch easily.
Positive ion formation
Positive mode charge exchanges produced in the chemical ionization source are generally :
Proton transfer ; M + [B+H]+ → [M+H]+ + B
Adduct formation ; M +X+ → [M+X]+
Echange de charge ; M + X+● → X + M+●
Energy of protonation
Chemical ionization is an acid-base reaction, in this reaction a molecule is a proton donor and the other one is a proton receptor. The ability of a B molecule to accept a proton is quantitatively described by its proton affinity (PA). The protonation process can be described as follows:
Bg + Hg+ → [BH]g+ ; – ΔHro = PA(B)
The proton affinity of the molecule B is the amount of energy produced by proton capture, it is expressed in joules / mol.
The collision of the molecule B with the protonated reactant gas makes it possible to approach the molecules and instantly forms an adduct.
Three situations can occur, either PA (B)> PA (G), molecule B carries the charge (the proton) after the degradation of the adduct, or PA (B) <PA (G), the molecule B is not protonated and it will not be observed in the mass spectrum. The last situation, the adduct is sufficiently stable until detection and it will be observed on the mass spectrum. The stability of the adduct is ensured by the hydrogen bonds and the proton which creates induced moments on the two molecules, this situation is generally observed, when the difference in the proton affinity of the molecules is not high.
In the first situation, molecule B is protonated and acquired the internal energy which is calculated from equation 2.
Eint(M+H) = PA(m) – PA(B)
According to this equation, the internal energy of the protonated molecular ion can be controlled by selecting the appropriate reactant gas according to their proton affinity (Table 1).
|Table 1 : Proton affinity|
Table 1 shows the proton affinity of the most used reactant gases in CI, in which hydrogen is the most exothermic of all the reactant gases, leading to considerable fragmentation. The use of hydrogen as a reactant gas is complicated by hydrogenation processes, which makes IC spectra less predictable, however, H2-CI has proven to be practical in special cases, especially for molecules that are very difficult to ionize. Methane is the gas widely used in CI, it allows to ionize most molecules because its proton affinity is low (Table 1), however the methane-CI spectra show a lot of fragment ions, and sometimes the molecular ions are not observed. The use of gases with high proton affinity significantly reduces fragmentation, such as ammonia or isobutane. Using the gases which have the high proton affinity, adduct ions are also observed, as is the case of ammonia because its proton affinity is high and it can easily form hydrogen bonds (Figure 1).
Figure 1: The IC spectra of allethrin with the different reactant gases, a) methane, b) isobutane, c) ammonia.
Negative ion formation
Generally all compounds can be ionized in positive mode, but the situation is not the same in the case of negative ions, all compounds do not produce negative ions in chemical ionization. However, many important compounds of environmental or biological interest can produce negative ions under good conditions. For such compounds, the negative mode is sometimes more efficient, more sensitive and selective. Negative ions can be formed by electron capture or by proton exchange with a charged species present in the plasma. In negative mode, a buffer gas is used (usually a common CI gas such as methane) to slow the electrons of the electron beam, until some electrons have just the right energy to be captured by the molecules of the electron beam analyte. The captured electron has very little kinetic energy of the order 1 eV to a few eV, the kinetic energy of the captured electrons does not bring any energy to the molecules, but the electron capture process is an endothermic one that brings about 2-5 eV which is enough to cleavage a covalent bonds. For electrons within too high kinetic energy, they are not captured by the molecule, but they can disrupt the electron cloud of the molecules. If the energy is too high, the disturbance can cause the fragmentation or even the loss of an electron (see also electron ionization), and the analytes are directly ionized by loss of the electron, these reactions are produced in the source CI which are the unwanted reactions.
Main reactions in negative mode.
(1) Proton transfer M + X– = (M-H)– + XH
(2) Charge exchange M + X–● = M–● + X
(3) Nucleophile addition M + X– = MX–
(4) Nucleophile replacement AB + X– = BX– + A
Primary ions produced by the reactant gas
The chemical ionization source is being used less and less in mass spectrometry compared to new modern ionization techniques such as MALDI or electrospray . The reactions produced in the CI source are numerous and complicated, but the CI source offers a good understanding of the chemical reactions in the gas phase that do not occur in solution. Because the interactions in the solution such as hydrophobicity, coulomb forces, π-π interactions, van der Waals forces … are strongly reduced or non-existent in the gas phase.
Let’s examine the case of methane used as a reactant gas. The reactions produced under the effect of electron bombardment are:
CH4 → CH4+●, CH3+, CH2+●, CH+, C+●, H2+●, H+
Then the chemical reactions that have been systematically studied.
CH4+. + CH4 → CH5+ + CH3●
CH3+ CH4 → C2H7+ → C2H5+ + H2
CH2+● + CH4 → C2H4+● +H2
CH2+● + CH4 → C2H3+ + H2 + H●
C2H3+ + CH4 → C3H5+ + H2
C2H5+ + CH4 → C3H7+ + H2
Atmospheric-pressure chemical ionization (APCI)
The abundance of ions produced in the CI source is strongly influenced by the temperature and pressure in the source. These reactions produce molecules that contribute to increasing the pressure of the source, but their pressure contributions are low and do not affect the reproductivity of the IC spectra. Chemical ionization at atmospheric pressure (APCI)   is a complementary method to electrospray. APCI does not generate multicharged ions, and operates at higher temperatures; it is commonly used to analyze polar and nonpolar compounds of low molecular weight (<1000 Da) and thermostable. APCI is a soft ionization method, it does not produce (or very little) fragmentation, and the ions produced are monocharged. The principle of APCI is to ionize the primary ions and then these ions exchange the charge with solvent molecules that exchange the charge in turn with the analytes (Figure 2), so it is based on the same principle of the chemical ionization but the reactions are carried out at atmospheric pressure. In the APCI source, the electron cloud is emitted by a corona discharge, the primary ions are produced from the gas in the atmosphere such as nitrogen, and oxygen.
Figure 2: Diagram of the APCI source
 Chemical ionization of amino acids C. W. Tsang, A. G. Harrison J. Am. Chem. Soc., 1976, 98 (6), pp 1301–1308
 Herman, J.A.; Harrison, A.G. Effect of Protonation Exothermicity on the CI Mass Spectra of Some Alkylbenzenes. Org. Mass Spectrom. 1981,16, 423-427.
 Yamashita, M. and J.B. Fenn. 1984. Electrospray ion-source—another variation on the free-jet theme. J. Phys. Chem. 88:4451-4459.
 Atmospheric pressure ionization (API) mass spectrometry. Solvent-mediated ionization of samples introduced in solution and in a liquid chromatograph effluent stream. Horning EC, Carroll DI, Dzidic I, Haegele KD, Horning MG, Stillwell RN. J Chromatogr Sci. 1974 Nov;12(11):725-9.
 ATMOSPHERIC PRESSURE IONIZATION MASS SPECTROMETRY Eric C. Huang Timothy Wachs James J. Conboy Jack D. Henion Anal. Chem., 1990, 62 (13), pp 713A–725A