Atmospheric-Pressure Photoionization Interface

Hsieh, Y. Wang, G. Integration of atmospheric pressure photoionization interfaces to HPLC-MS/MS for pharmaceutical analysis. Am Pharm Rev 2004, 7, 88-93. 

The two most common LG/MS interfaces used for routine quantitative analyses are APCI and APT electrospray. The principles of these techniques in direct infusion analyses have been described earlier (see Sections 3.3 and 3.4). As APTelectrospray has a broader application profile, its use is more widespread than APCI. Other configurations including El, atmospheric pressure photoionization (APPl), and thermospray interfaces with liquid chromatographs are available but are less commonly used for high throughput or routine analysis. 

ESI operating in the negative ion (Nl) mode has been the interface most widely used for the analysis of anionic PFCs. In addition, ESI has also been optimized for the determination of neutral compounds, such as the sulphonamides PFOSA, Et-PFOSA, and t-Bu-PFOS. The use of atmospheric pressure photoionization (APPI) has been explored by Takino and collaborators [88]. The authors found the main advantage of this technology to be the absence of matrix effects, but the limits of detection were considerably higher than those obtained by LC-ESTMS/MS. 

Different methods are used to tackle these problems [10-13], Some of these coupling methods, such as moving-belt coupling or the particle beam (PB) interface, are based on the selective vaporization of the elution solvent before it enters the spectrometer source. Other methods such as direct liquid introduction (DLI) [14] or continuous flow FAB (CF-FAB) rely on reducing the flow of the liquid that is introduced into the interface in order to obtain a flow that can be directly pumped into the source. In order to achieve this it must be reduced to one-twentieth of the value calculated above, that is 5 pi min. These flows are obtained from HPLC capillary columns or from a flow split at the outlet of classical HPLC columns. Finally, a series of HPLC/MS coupling methods such as thermospray (TSP), electrospray (ESI), atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI) can tolerate flow rates of about 1 ml min 1 without requiring a flow split. Introducing the eluent entirely into the interface increases the detection sensitivity of these methods. ESI can accept flow rates from 10 nl min-1 levels to... 

Earlier methods of ionization applied to carotenoids, including electron impact (El), chemical ionization (Cl), a particle beam interface with El or Cl, and continuous-flow fast atom bombardment (CF-FAB), have been comprehensively reviewed elsewhere (van Breemen, 1996, 1997 Pajkovic and van Breemen, 2005). These techniques have generally been replaced by softer ionization techniques like electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), and more recently atmospheric pressure photoionization (APPI). It should be noted that ESI, APCI, and APPI can be used as ionization methods with a direct infusion of an analyte in solution (i.e. not interfaced with an HPLC system), or as the interface between the HPEC and the MS. In contrast, matrix-assisted laser desorption ionization (MALDI) cannot be used directly with HPEC. 

There are other LC/MS interfaces that are less commonly used than ESI and APCI, but are often employed by researchers for analysis of nonpolar or neutral compounds, including particle beam and atmospheric pressure photoionization (APPI). 

In the current LC-MS interfaces, i.e., ESI and atmospheric-pressure chemical ionization (APCl), interfacing and analyte ionization are closely interrelated. The column effluent is nebulized and ionization takes place in the aerosol generated, either with or without a primary external source of ionization. Ionization mechanisms of ESI, APCl, and atmospheric-pressure photoionization (APPl) are discussed in this chapter. 

Moreover, besides ESI, which will remain the preferred ionization technique, other atmospheric pressure ionization modes such as atmospheric pressure chemical ionization (APCI) and, more recently, atmospheric pressure photoionization (APPI) can be used as interesting alternatives. These interfaces might be of great interest in CE-MS, since they allow different selectivities and are more tolerant than ESI with respect to nonvolatile electrolytes. However, the lack of commercially available interfaces appears to be one of the limiting factors of these ionization techniques for CE analysis. 

Atmospheric-pressure photoionization (APPI), which was first applied as an LC-MS interface in 2000, is a relatively new ionization technique. The ionization process is initiated by an ultraviolet lamp (krypton discharge lamp), which emits 10.0 and 10.6 eV photons. Any compounds that have ionization energies below 10 or... 

Finally, the Appendix shows schematic representations of the principle of operation of some of the ionization processes presented. " Among these are the theory of ESI, atmospheric pressure chemical ionization (APCI), and atmospheric pressure photoionization (APPI). Also shown are schematics of the ionizers and typical experimental conditions for the APCI and APPI sources as well as that of an ESI-APCl mixed source. It should be noted that these schematics are for sources that are interfaced with a mass spectrometer but are similar to IMS interfaces. 

Most early reports of PI detection for LC were simply adaptations of the PI GC detector, i.e., simple detection only, with no complementary MS information. The only exception (Revel skii 1991) involved some experiments that did not explore direct LC-MS coupling, but rather its feasibility in which vaporized samples were transported to an atmospheric pressure photoionization (APPI) source interfaced to a quadrupole MS. Encouraging results were obtained with the exception that, when abundant solvent vapor (water or methanol) was added, a significant decrease in the APPI response for the model analytes was observed. This phenomenon is stiU important for modem LC-APPI, as discussed below. 

The successful on-line interfacing of several ion sources has made them dominant players in quantitative analyses using mass spectrometry. These include electron ionization (El) and chemical ionization (Cl) both coupled to GC, and the atmospheric pressure ionization (API) methods of atmospheric pressure chemical ionization (APCI) atmospheric pressure photoionization (APPI), and electrospray ionization (ESI) coupled to LC. In addition, matrix assisted laser desorption ionization (MALDI) is seeing increased application in off-line LC/MS applications. 

The mostly used interfaces in LC-MS are electrospray ionization, atmospheric pressure chemical ionization (APCI), atmospheric pressure photoionization (APPI), and inductively coupled plasma ionization (ICP). While ICP is mostly used in the determination of metals (for elemental analysis) and has its specific applications,... 

Miniaturized ESI interfaces (nanospray electrospray ionization, nanoESI) match the dimensions of microfluidic chips. On-line couphng of microchips with ESI can be accomplished using different interface geometries blunt end, comer outlet, external capillary, external emitter, or monolithic emitter [27], some of which resemble the nanoESI emitters used in CE-MS (see also Chapter 6). In fact, on-chip capillary channels are often used as CE or LC separation columns, and directly linked with the nanoESI emitters. Atmospheric pressure chemical ionization (APCI) and photoionization (APPI) have also been subject to miniaturization but they have not attracted as much attention when it comes to hyphenation with microchips [28]. This situation may change when the novel nanoAPCI interfaces [29] are perfected, providing the way to transmit and ionize non-polar analytes at low flow rates. 

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