Atmospheric pressure photoionization (APPI) has been successfully demonstrated to provide high sensitivity to LC-MS analysis. A vacuum-ultraviolet lamp designed for photoionization detection in gas chromatography is used as a source of 10-eV photons. The mixture of samples and solvent eluting from an HPLC is fully evaporated prior to introduction into the photoionization region. In the new method, large quantities of an ionizable dopant are added to the vapor generated from the LC eluant, allowing for a great abundance of dopant photoions to be produced. Because the ion source is at atmospheric pressure, and the collision rate is high, the dopant photoions react to completion with solvent and analyte molecules present in the ion source. Using APPI, at an LC flow rate of 200 microL/min, it is possible to obtain analyte signal intensities 8 times as high as those obtainable with a commercially available corona discharge-atmospheric pressure chemical ionization source.

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In this paper, the effects of solvent flow, dopant flow, and lamp power on proton transfer ionization in dopant-assisted (DA) atmospheric pressure photoionization (APPI) are investigated. A broad theoretical framework is presented, describing the primary photoionization process, the formation of protonated-solvent cluster ions, and the balance between analyte ion creation via proton transfer and loss via recombination. The principal experimental test system utilized methanol as the solvent, toluene as the dopant, and acridine as the analyte. Comparisons are made between acridine and a less basic compound, 9-methylanthracene (9-MA). Experimental determinations of the trends in the analyte MH ϩ signal and the total ion current (TIC) with variations in the subject parameters are provided. Experimental results and theory demonstrate that both the analyte signal and the TIC approach asymptotic limits with increases in dopant flow and/or lamp current (two factors which dictate the rate of photoion generation). The data show that these limits are lowered at higher solvent flow rates. These results are attributed to the recombination loss process, the rate of which increases with the second power of ion concentration. We deduce that the recombination rate constant increases with solvent flow rate, a consequence of the growth of ion-solvent clusters. Cluster growth is also believed to be a factor in the dramatic loss of sensitivity for 9-MA that occurs as the solvent flow is raised, because larger protonated-solvent cluster ions have greater solvation energies and may be unreactive with compounds having low gas-phase basicity and/or low solvation energy. (J Am Soc Mass Spectrom 2005, 16, 1275-1290) © 2005 American Society for Mass Spectrometry P hotoionization (PI) is the latest means of ionization to be incorporated into atmospheric pressure ionization (API) sources for liquid chromatography-mass spectrometry (LC-MS). The original motivation for the development of atmospheric pressure photoionization (APPI) sources was the demand for a method or device capable of expanding the range of compounds amenable to LC-MS to include nonpolar compounds not readily ionized by either electrospray [1,2] or atmospheric pressure chemical ionization (APCI) [3,4]. In recent years, two approaches towards utilizing PI at atmospheric pressure have emerged: dopant-assisted (DA) APPI [5] and direct APPI [6]. Recent review papers provide details of the two APPI-MS methods [7,8]. This paper is concerned mainly with DA-APPI.As is often the case for new technologies, the practical application of DA-APPI has outpaced the development of detailed knowledge regarding the mechanisms responsible for its performance. DA-APPI relies upon gas-phase ion-molecule reactions to place a charge on neutral analytes, so it is especially important that these reactions be well understood. The groups of Kostiainen and Bruins have completed several studies of the reaction chemistry of DA-APPI and the effects of solvent and dopant composition on the ionization effici...

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Atmospheric pressure photoionization (APPI) is capable of ionizing nonpolar compounds in LC/MS, through charge exchange reactions following photoionization of a dopant. Recently, several novel dopants-chlorobenzene, bromobenzene, 2,4-difluoroanisole, and 3-(trifluoromethyl)anisole-have been identified as having properties making them wellsuited to serve as dopants for charge exchange ionization under reversed-phase LC conditions. Here, we report the results of experiments comparing their effectiveness to that of established dopants-toluene, anisole, and a toluene/anisole mixture, for the charge exchange ionization of model nonpolar compounds-the 16 polycyclic aromatic hydrocarbons (PAHs) identified by the US EPA as priority pollutants-when using a conventional reversed-phase LC method. Chloro-and bromobenzene were found to be much more effective than toluene for all the PAHs, due to the relatively low reactivity of their photoions with the solvent. Their overall performance was also better than that of anisole, due to anisole's ineffectiveness toward higher-IE compounds. Further, the experiments revealed that anisole's performance for higher-IE compounds can be dramatically improved by introducing it as a dilute solution in toluene, rather than neat. The two fluoroanisoles provided the highest overall sensitivity, by a slim margin, when introduced as dilute solutions in either chloro-or bromobenzene. With APPI, analyte ionization is mostly due to ionmolecule reactions following photoionization of a primary reagent, typically a dopant [4]. Analyte ionization can occur in positive mode through either proton transfer or charge exchange (electron-transfer) reaction pathways. This article regards the ionization of nonpolar, low proton affinity compounds via charge exchange with dopant radical cations.In APPI, for charge exchange ionization to occur the dopant's ionization energy (IE) must be greater than that of the analyte and to be efficient its radical cations must not be consumed through reactions with the solvent, its own neutrals, or impurities. Toluene was the first dopant to be used for charge exchange ionization in APPI [1], and it has a relatively high IE (8.83 eV), making it suitable for a wide range of analytes (all IE values are from reference [5]). In practice, however, toluene is only an efficient charge exchange dopant under normal-phase [6,7] and/or low-flow conditions[8] because its radical cations are rapidly consumed in reactions with methanol and acetonitrile at conventional LC flow rates [6, 9, 10]. Some other dopant is then required for efficient charge exchange ionization with reversed-phase LC methods. The usual alternative to toluene for promoting charge exchange ionization is anisole, whose photoions are stable in the presence of methanol and acetonitrile [11]. Anisole, however, has a relatively low IE (8.20 eV), restricting its applicability. Mixtures of anisole and toluene have been utilized by Itoh et al. as dopants to promote charge exchange ionization under reversed-phase conditions, i...

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The sensitivity of dopant-assisted atmospheric pressure photoionization (DA-APPI) for LC/MS is generally reduced at higher solvent flow rates. Theory suggests that quenching of excited-state precursors to the dopant ions, via collisions with vaporized solvent molecules, may be one mechanism responsible for this trend. To ascertain if the primary rate of ionization is affected by quenching, experiments were performed utilizing an ionization detector to determine the primary ion current generated by irradiating vaporized mixtures of toluene dopant and methanol solvent. The results indicate that no loss of primary ion current occurs as the solvent flow is increased, provided the dopant-to-solvent ratio is held constant. Additional primary ion current can always be generated by increasing the dopant flow rate and/or the lamp power. Thus, quenching of excited-state precursors to the dopant ions, leading to a reduction in the primary rate of ionization, is not the mechanism responsible for the observed loss of sensitivity at higher liquid solvent flow rates. (J Am Soc Mass Spectrom 2006, 17, 130 -138)

It is well documented since the early days of the development of atmospheric pressure ionization methods, which operate in the gas phase, that cluster ions are ubiquitous. This holds true for atmospheric pressure chemical ionization, as well as for more recent techniques, such as atmospheric pressure photoionization, direct analysis in real time, and many more. In fact, it is well established that cluster ions are the primary carriers of the net charge generated. Nevertheless, cluster ion chemistry has only been sporadically included in the numerous proposed ionization mechanisms leading to charged target analytes, which are often protonated molecules. This paper series, consisting of two parts, attempts to highlight the role of cluster ion chemistry with regard to the generation of analyte ions. In addition, the impact of the changing reaction matrix and the non-thermal collisions of ions en route from the atmospheric pressure ion source to the high vacuum analyzer region are discussed. This work addresses such issues as extent of protonation versus deuteration, the extent of analyte fragmentation, as well as highly variable ionization efficiencies, among others. In Part 1, the nature of the reagent ion generation is examined, as well as the extent of thermodynamic versus kinetic control of the resulting ion population entering the analyzer region.