| ESI is the best choice for polar compounds such as drugs and is by far the best choice for larger molecules, such as peptides and proteins. For other compounds, APCI and APPI should be the preferred choice, with an advantage toward APPI in many important respects, except at very high flow rates (for example, 1 mL/min) and for small molecules such as smaller alkanes (smaller than hexane) and halocarbons.  |
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| APPI mechanism | The hallmark of threshold photoionization (PI) is the ability to choose a narrow band of ionization energy that is sufficiently high to ionize and detect most molecules of interest, yet sufficiently low to avoid detection of the most common constituents of air. The figure illustrates the principle behind these benefits. Syagen PI sources impart an energy that is higher than the ionization potentials (IPs) of most target molecules, yet is lower than the IPs of the most common atmospheric constituents as well as most common solvents. Hence, these potential interferents go undetected, enabling significantly greater dynamic range for detecting and measuring very low concentration molecules. Furthermore, because molecules of interest are ionized near their IP thresholds, there is minimal fragmentation to clutter a mass spectrum. These performance features provide tremendous benefits for analyzing mixtures and samples in complex matrices. The fundamental process in photoionization is the absorption of a high-energy photon by the molecule and subsequent ejection of an electron. In direct APPI, this process occurs for the analyte molecule, forming the molecular radical cation M. + . The analyte radical cation can be detected as M. + or it can react with surrounding molecules and be detected as another ion. The most common reaction is the abstraction of a hydrogen atom from the abundant solvent to form the stable [M+H]+ cation, which is usually the observed ionIn dopant APPI [or photoionization-induced APCI ], a quantity of photoionizable molecules (for example, toluene or acetone) is introduced into the sample stream to create a source of charge carriers. Use of a photoionizable solvent achieves the same effect. The dopant or solvent ions can then react with neutral analyte molecules via proton transfer or charge exchange reactions. The previously mentioned dopant mechanism simplifies the dopant process. In fact, there can be extensive ion–molecule chemistry between dopant and solvent before the analyte becomes ionized. APPI also can produce negative ions by creating a high abundance of thermal electrons from dopant or solvent ionization, or by photons striking metal surfaces in the ionization source. 
Two commercially available APPI sources take different approaches to photoionization. One source is designed specifically for dopant APPI, including a reaction tube in which dopant-ion reactions are enhanced (MDS Sciex, Concord, Ontario, Canada). The other source is designed for direct APPI, consisting of an open geometry with a high intensity lamp (Syagen, Tustin, California); however dopant-APPI also can be performed with this source.  The process of direct APPI is not as prone to charge-competition. Photons are egalitarian, crossing any molecule in their path. In this regard, as shown in Figure 1, an analyte molecule X has just as great of a chance of being ionized whether or not a lower ionization potential molecule Y is present. Consequently, APPI is much less prone to ion suppression than either ESI or APCI. Dopant APPI is similar to APCI, however, in that charge carriers are created to promote analyte ionization, and are therefore somewhat susceptible to ion suppression. This is not to say that direct APPI is entirely immune to ion suppression, because once photoions are formed they can undergo further ion molecule chemistry. However, the desired ions are formed initially, as opposed to APCI and ESI, where competition for charge can prevent the desired ions from forming in any useful yield. |
| Factors affecting APPI ionization | As molecules with ionization potentials (IPs) lower than the Kr lamp energies of 10.0 and 10.6 eV will be ionized efficiently, the factors that most affect APPI sensitivity are solvent properties and source conditions. Solvent has the potential to interfere with analyte ionization, because it can compete for the absorption of photons. If the solvent IP is greater than the lamp photon energy and has an appreciable photon-absorption cross section, then the photon can be absorbed and the energy dissipates uselessly. Solvents with high IPs include the aqueous reversed-phase solvents water (IP = 12.6 eV), acetonitrile (12.2 eV), and methanol (10.8 eV). If the solvent IP is comparable to or less than the lamp energy, then the absorbed photon can ionize the solvent molecule, producing a charge carrier that can then go on to ionize analyte ions. Solvents with lower IPs include normal-phase or nonaqueous reversed-phase solvents such as hexane (IP = 10.1 eV), isooctane (9.86 eV), and isopropyl alcohol (10.2 eV). It should be noted that solvent dimers, which are present in about 1–100 ppm abundance (depending upon temperature and flow rate) have about 1 eV lower IP than the solvent monomer and are often ionizable. Methanol (dimer IP = 9.74 eV) is an example of this, and therefore the use of methanol enhances APPI, in contrast to acetonitrile, for which the dimer IP is still too high to ionize. Acetonitrile has the additional disadvantage of having a very high absorption cross section and is believed to participate adversely in ion-molecule chemistry. Because APCI depends upon the solvent to generate charge carriers, its sensitivity diminishes at lower flow rates. This is opposite to APPI, which excels at low flow rates, because it does not necessarily require the solvent for ionization. Moreover, lower flow rates result in less solvent absorption of photons. Additionally, APPI sensitivity can be compromised even at high flow rates, as solvent photoabsorption can compete with analyte photoionization. For very high flow rates (for example, 1 mL/min), APCI typically will surpass APPI in sensitivity. However, this can be equalized by using dopants or mobile-phase solvents (for example, hexane, isopropyl alcohol) that photoionize. Competition for charge can also lead to ion suppression. The mechanism of photoionization — ejection of an electron following photon absorption by a molecule — is independent of the surrounding molecules, thereby reducing ion suppression effects. |
| Portrayal of range of ionization by ESI, APCI, and APPI as a function of compound polarity and molecular weight. | Detection limits of about 1 pg have been measured, comparable to APCI and ESI. The APPI source is linear over at least 5 orders of magnitude. |
| source: http://chromatographyonline.findpharma.com/lcgc/article/articleDetail.jsp?id=504702&pageID=1&sk=&date= http://www.syagen.com/photoionization.asp |
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