Dopant APPI

DA-APPI dopant-assisted atmospheric-pressure photoionization... 

What role does the dopant play in APPI (Ionization of molecules having a low photoionization cross section (probability) has been shown to be enhanced by the use of a dopant that is introduced into the vaporized plume of analyte molecules the dopant is selected on the basis of its high UV absorptivity and serves as a charge transfer reagent). 

Robb, D. B., and Blades, M. W. (2006). Factors affecting primary ionization in dopant-assisted atmospheric pressure photoionization (DA-APPI) for LC/MS. J. Am. Soc. Mass Spectrom. 17, 130-138. 

APPI is a relatively recent development compared with the other techniques. Here, ionisation is achieved photochemically, either directly or mediated by a dopant such as acetone added to the eluent. Both even- and the less stable odd-electron ions (e.g. M ) may be formed. At the time of writing, the mechanisms involved and scope of the technique are still not fully understood. What is apparent is that it provides a complementary technique to ESI and APCI. 

Figure 6.1 shows the mass spectmm of an impurity run in the positive APPI mode and shows both at miz 352 and MH miz 353. This is an example where the mechanisms of proton transfer and electron transfer are both taking place. This can be confusing when dealing with complete unknowns and demonstrates why it is unsuitable for routine use in an open access multi-user environment or by inexperienced users. A better understanding of the processes involved and the role of mobile phase and dopant is required before this can be put to routine use. There are a number of papers published on this topic [20, 21]. 

It is possible to successfully perform dopant-assisted DA-APLI upon addition of a dopant (e.g., toluene or anisole). DA-APLI currently shows the same performance as DA-APPI. 

However, the direct ionization of the analyte is generally characterized by a weak efficiency. This can be partially explained by the solvent property to absorb photons producing photoexcitation without ionization. This reduces the number of photons available for the direct ionization of the sample, thus reducing the ionization efficiency. Consequently, ionization using doping molecules has also been described. It has indeed been shown that dopant at relatively high concentrations in comparison with the sample allows generally an increase in the efficiency of ionization from 10 to 100 times. This indicates that the process is initiated by the photoionization of the dopant. The dopant must be photoionizable and able to act as intermediates to ionize the sample molecules. The most commonly used dopants are toluene and acetone. Thus, two distinct APPI sources have been described direct APPI and dopant APPI. 

APPI is also efficient in negative ion mode, in so far as a dopant is used [84], Indeed, in this ionization mode, analysis made without dopant dramatically decreases the sensitivity. All the reactions leading to the ionization of the analytes are initiated by thermal electrons produced with the photoionization of the dopant. Hence, solvents of high positive electron affinity, for example halogenated solvents, inhibit the ionization of all the analytes because these solvents capture all the available thermal electrons in the source. 

Compared with APCI, APPI is more sensitive to the experimental conditions. Properties of solvents, additives, dopants or buffer components can strongly influence the selectivity or sensitivity of the detection of analytes. Nevertheless, this technique allows the ionization of compounds not detectable in APCI or ESI, mainly non-polar compounds. For these last compounds, APPI is a valuable alternative. Thus, APPI is a complementary technique to APCI and ESI. However, for a given substance it remains difficult to predict which ionization source (APPI, APCI or ESI) will give the best results. Only preliminary tests will allow the choice of the best ionization source. APPI appears to be efficient for some compound classes such as flavonoids, steroids, drugs and their metabolites, pesticides, polyaromatic hydrocarbons, etc. [85],... 

In the APPI method of ionization, the solvent is vaporized in a heated nebulizer and the gaseous analytes are then ionized with photons from a lamp (Rivera et ah, 2011). It has been observed that certain solvents, called dopants, enhance the ionization of analytes via this technique. To date only one study has been published with carotenoids and APPI (Rivera et ah, 2011). APPI was compared to ESI and APCI as ionization techniques, and the authors observed that APPI positive produced approximately a 2- to 4-fold greater total ion signal for lycopene and (3-carotene as compared to APCI positive and ESI positive. In contrast, APCI positive outperformed APPI positive for a number of xantho-phylls and phytoene and phytofluene. 

APPI is derived from APCI, but instead of the corona discharge needle, the ionization takes place after irradiation with a krypton lamp that emits photons of 10.0-10.6 electron volt. Different methods with and without dopant have been recommended. APPI, in combination with LC, has been used to analyze glycosphingohpids (31). In addition, APPI has been reported to be more sensitive and efficient than APCI and ESI for the analysis of fatty acid esters and acylglycerols (32, 33). Because the method has not found widespread use to date, it is too early to estimate its potential. 

This is the direct-APPI approach, promoted by the group of Syage [66], In the observations and experimental setup of the group of Bruins [61], the direct-APPI process is not sufficiently efficient. Therefore, an easily ionizable compound, the dopant D, is added to the mobile phase or to the nebulizing gas to enhance the response. Toluene [61] or anisole [68] are frequently used as dopant. With a dopant, the APPI takes place via a charge-exchange reaction between the dopant molecular ion and the analyte molecule ... 

Whereas in both direct-APPI and dopant-APPI, an analyte molecular ion NT would be expected, rather than a protonated molecule [M+H] is observed, for quite many analytes. This is assumed to be due to interaction with the mobile-phase constituents. In the direct-APPI approach, the protonated molecule is formed due to a reaction of the analyte molecular ion with the solvent S ... 

In dopant-APPI, the formation of [M+H] is attributed to internal proton rearrangement in the solvated dopant ion clusters [69] ... 

T. J. KauppUa, R. Kostiainen, A.P. Bmins, Anisole, a new dopant for APPI-MS of low proton affinity, low ionization energy compounds. Rapid Commun. Mass Spectrom., 18 (2004) 808. 

D.B. Robb, M.W. Blades, Effects of solvent flow, dopant flow, and lamp current on dopant-assisted APPI for LC—MS. Ionization via proton transfer, J. Am. Soc. Mass Spectrom., 16 (2005) 1275. 

APPI interface is promising since the common LC solvents are characterized by high first ionization potentials with the consequence that selective ionization of the analytes may occur. Addition of a dopant to the mobile phase such as acetone or toluene offers increased selectivity. 

APPI is mainly used as an alternative to normal corona discharge APCI. APPI has produced equal or better detection limits compared to APCI in selected applications (Wanget al., 2005), however, theionization process in APPI depends directly on the solvent, dopant, nebulizing gas, and impurities in the gas and surrounding atmosphere, as well as the analyte itself (Yang and Henion, 2002). 

The absorption of a photon by the molecule and the ejection of an electron forms a radical cation. Better sensitivities have been reported with the addition of dopants such as toluene or acetone. The mechanism of ionization is not fully understood, but two different mechanisms can occur (i) dopant radical cations react with the analyte by charge transfer or (ii) the dopant radical cation can ionize the solvent molecules by proton transfer, which can then ionize the analyte. APPI can also be performed in the negative mode. As APCI, APPI can handle a large range of analytes. The performanee of APPI is dependant on the flow rate, and better sensitivities, compared to APCI, have been reported at lower flow rates. Because APCI and APPI are gas ionization processes, it appears that compared to ESI they are less or differently affected by matrix effects (Robb and Blades, 2008). APPI is attractive for a large variety of neutral analytes such as steroids (Cai et ah, 2005). 

The next gas-phase ionization technique for LC-MS is APPI. It is a relatively new method, and its strengths and weaknesses will become clear as the number of applications grows over time. Thus far APPI appears to work best at flow rates of 100-200 pi min At higher flow rates ionization efficiency is reduced. To increase sensitivity a dopant such as acetone, toluene, or anisole is introduced into the ionization region. First, the dopant is ionized by photons and next the dopant ions undergo ion-molecule reactions with ultimate ionization of the sample. Solvent components can have a major influence on the cascade of ion-molecule reactions, and should be selected with care. 

For these classes of substances, other methods have been developed, such as the coupling of ESI with an electrochemical cell [20-31], the coordination ion-spray [31-46], or the dissociative electron-capture ionization [37-41]. The APPI or the dopant-assisted (DA) APPI presented by Syage et al. [42, 43] and Robb et al. [44,45], respectively, are relatively new methods for photoionization (PI) of nonpolar substances by means of vacuum ultraviolet (VUV) radiation. Both techniques are based on photoionization, which is also used in ion mobility mass spectrometry [46-49] and in the photoionization detector (PID) [50- 52]. 

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