Chemical Ionization Mass Spectrometry: Theory and Applications

Abstract

Chemical ionization mass spectrometry (CIMS) is a technique for forming ions of the compound of interest (analyte, A) by ion/molecule reactions from reactant ions of a reagent gas that is generally present in a much greater abundance than the analyte. The reactant ions are generally produced by electron ionization (EI) of the reagent gas. The ions produced by EI often react with the large excess of the reagent gas to form the actual reagent ions that react with the analyte. CIMS is performed with both positively and negatively charged reactant ions. The most common ion/molecule reactions in CIMS are proton transfer (which forms AH + or [ A − H ] − ions), hydride transfer (which forms [ A − H ] + ions), charge or electron transfer (which forms A +• or A −• ions), and adduct formation or attachment (which forms [A + R] + or [A + R] − ions). Fragment ions from decompositions of these AH + , A ±• , [A − H] ± , and [A + R] ± ions are frequently observed. The extent of fragmentation can be controlled by the choice of reagent gas used and can be predicted to some extent from ionic thermochemical data. Collisionally stabilized electron capture at high pressures (to form A −• ions) is often classified as chemical ionization (CI). The most common use of CIMS in analytical mass spectrometry is to obtain simplified mass spectra of compounds, often one species spectra, which can be used for quantitative analysis of mixtures. CIMS can be performed with any type of mass spectrometer (quadrupole, magnetic, time‐of‐flight (TOF), Fourier transform ion cyclotron resonance (FTICR), ion trap) and CIMS capabilities are routinely available on many commercial instruments. With ion trap or FTICR mass spectrometers, it is possible to select specific reactant ions. It is generally considered that CI and EI sensitivities are approximately the same in the positive ion mode and that electron capture CI at high pressures for compounds with high electronegativities gives a much greater sensitivity than other EI or CI techniques. CIMS has the same general limitations as electron ionization mass spectrometry (EIMS) on the volatility and thermal stability of the compound being analyzed. However, direct insertion of the sample into the source of the mass spectrometer allows the analysis of relatively involatile and thermally unstable compounds.

The use of mass spectrometry to analyze dried blood spots

“…Although the authors claimed negative‐ion chemical ionization (NICI) as ionization technique (NICI implies negative ion/molecule reactions, for example, proton transfer or adduct formation), the sole use of methane as reagent gas makes NICI very unlikely because methane does not lead to stable negative ions in sufficient concentrations after EI. A more exact terminology is, therefore, electron capture negative ionization (ECNI), with ions produced by capture of thermal electrons; those electrons are provided subsequently to methane EI (Harrison, ; Munson, ). A major advantage of ECNI is that it is highly sensitive for analysis of halogenated compounds due to the high electronegativity of halogens.…”

Isobutane Made Practical as a Reagent Gas for Chemical Ionization Mass Spectrometry

“…Methane was the first reagent gas used for CI and remains by far the most common, almost to the total exclusion of other gases in contemporary experiments. The principal positive reagent ions from methane, CH 5 + and C 2 H 5 + , react with almost all organic molecules, and methane CI spectra are largely independent of reagent gas pressure in the ion source [2,3]. When resonance electron capture (EC) ionization was adapted for negative chemical ionization (NCI) mass spectrometry, methane was used as reagent gas to thermalize electrons [4][5][6].…”

“…The isobutane reagent ion C 3 H 7 + reacts with i-C 4 H 10 to form the reagent ion t-C 4 H 9 + . The changing pressure of i-C 4 H 10 affects the ratio between reagent ions, which have different acidities and produce differing amounts of fragmentation [3]. Because modern commercial instrumentation for CI-MS does not directly measure reagent gas pressure in the source, conditions cannot be duplicated easily between instruments.…”

Compound-Specific Chlorine Isotope Analysis of Organochlorine Pesticides by Gas Chromatography-Negative Chemical Ionization Mass Spectrometry

“…In negative chemical ionization (NCI), the sample molecules do not directly interact with electrons emitted from the filament, but reaction gas molecules collide with the electrons to generate hot electrons, which are trapped by the sample molecules to generate negative ions, achieving ionization. NCI can detect compounds with strong electronegativity, such as organochlorines, that readily capture electrons, resulting in high sensitivity and selectivity [ 30 ]. The characteristic ions of α -HCH appeared at m/z 35 (Cl − ) and 71 (HCl 2 − ), while the relative abundance of ions in the high mass region was small ( Figure 2(b) ).…”