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Atmospheric pressure chemical ionization (APCI) is an ionization method used in mass spectrometry (commonly LC-MS) which utilizes gas-phase ion-molecule reactions at atmospheric pressure (105 Pa). It is an ionization method that is similar to chemical ionization where primary ions are produced on a solvent spray. APCI is mainly used with polar and relatively less polar thermally stable compounds with molecular weight less than 1500 Da. APCI is typically coupled with high-performance liquid chromatography (HPLC) cite. The application with HPLC has gained a large popularity in trace analysis detection such as steroids and pesticides and also in pharmacology for drug metabolites.

Instrument structure
A typical APCI usually consists of three main parts: a nebulizer probe which can be heated to 350-500 oC; an ionization region with corona discharge (5-10 kV) under atmospheric pressure, and an ion-transfer region under intermediate pressure. The analyte in solution is introduced from a direct inlet probe or a liquid chromatography (LC) eluate into a pneumatic nebulizer with an flow rate between 0.2 and 2 mL/min. In the heated nebulizer, the LC eluate coaxially flows with nebulizer N2 gas and sheath N2 gas. A mist of fine droplets emerges and are converted into a gas stream by the combination of heat and gas flow in the nebulizer. Once the gas stream arrives the ionization region under atmospheric pressure, ionization occurs at corona discharge which is 2 to 3 kV potential different to the exit counter-electrode. Sample ions then pass through a small orifice skimmer into the ion-transfer region. Ions may be transported through additional skimmer and ion-focusing lenses into a mass analyzer for subsequent mass analysis.

Ionization mechanism
APCI is based on chemical ionization by ion-molecule or electron capture reactions that are carried out in an ion source operating at atmospheric pressure.

The ionization can either be carried out in positive or negative ionization mode. In the positive mode, the relative proton affinities of the reactant ions and the gaseous analyte molecules allow either proton transfer or adduction of reactant gas ions to produce the ions of the molecular species. In the negative mode, however, the ions are produced by either proton abstraction or adduct formation.

In most cases, the evaporated mobile phase acts as the ionization gas and reactant ions are formed because of the effect of the corona discharge on the nebulized solvent. Generally, the primary ions formed by the corona discharge are ions such as a positively charged nitrogen or oxygen radical which can then form secondary reactant gas ions though collision with vaporized solvent molecules. Finally, a proton transfer from the charged solvent molecules to analyte molecules to produce [M+H]+.

In a major distinction from chemical ionization, the electrons needed for the primary ionization are not produced by a heated filament, as a heated filament cannot be used under atmospheric pressure conditions. Instead, the ionization must occur using either corona discharges or β- particle emitters, which are both electron sources capable of handling the presence of corrosive or oxidizing gases.

Primary and secondary reagent ions formation :

N2 + e → N2+ + 2e

N2+ + 2N2 → N4+ + N2

N4+ + H2O → H2O+ + 2N2

H2O+ + H2O → H3O+ + OH•

H3O+ + H2O + N2 → H+(H2O)2 + N2

H+(H2O)n-1 + H2O + N2 → H+(H2O)n + N2

Product ions formation :

H+(H2O)n + M → MH+(H2O)m + (n-m)H2O

History
The first atmospheric pressure ionization source was developed by Horning, Carroll and their co-works in the 1970s at the Baylor College of Medicine (Houston, TX). Initially, 63Ni foil was used as a source of electrons to perform ionization. Latterly in 1975, corona discharge electrode was used, which had a larger dynamic response range. APCI with the corona discharge electrode became the model for modern commercially available APCI interfaces.

APCI was applied to GC/MS and LC/MS also by Horning's group in 1975. They ionized the mixture of solvent and analyte molecules from the LC that was caporized in a heated block, and demonstrated the attributes of high sensitivity and simple mass spectra that are now associated with this method. The coupling of APCI and LC/MS became famous in the later decades. large attention, and became popular in the later decades.

Advantages
Ionization of the substrate is very efficient as it occurs at atmospheric pressure, and thus has a high collision frequency. Additionally, APCI considerably reduces the thermal decomposition of the analyte because of the rapid desolvation and vaporization of the droplets in the initial stages of the ionization. This combination of factors most typically results in the production of ions of the molecular species with fewer fragmentations than many other ionization methods, making it a soft ionization method.

Another advantage to using APCI over other ionization methods is that it allows for the high flow rates typical of standard bore HPLC (0.2-2.0mL/min) to be used directly, often without diverting the larger fraction of volume to waste. Additionally, APCI can often be performed in a modified ESI source. The ionization occurs in the gas phase, unlike ESI, where the ionization occurs in the liquid phase. A potential advantage of APCI is that it is possible to use a nonpolar solvent as a mobile phase solution, instead of a polar solvent, because the solvent and molecules of interest are converted to a gaseous state before reaching the corona discharge pin.