APCI review

This chapter is mainly limited to direct API-MS. For LC-API-MS, see Section 73.3.2. APCI, ESI and APPI complement each other in chemical analyses. API-MS was reviewed repeatedly [124,125], and has been the subject of a recent monograph [126]. 

APPI and corona discharge-APCI methods were compared [164], A review of photoionisation and photodissociation methods in MS has appeared [165]. 

The mobile phase in LC-MS may play several roles active carrier (to be removed prior to MS), transfer medium (for nonvolatile and/or thermally labile analytes from the liquid to the gas state), or essential constituent (analyte ionisation). As LC is often selected for the separation of involatile and thermally labile samples, ionisation methods different from those predominantly used in GC-MS are required. Only a few of the ionisation methods originally developed in MS, notably El and Cl, have found application in LC-MS, whereas other methods have been modified (e.g. FAB, PI) or remained incompatible (e.g. FD). Other ionisation methods (TSP, ESI, APCI, SSI) have even emerged in close relationship to LC-MS interfacing. With these methods, ion formation is achieved within the LC-MS interface, i.e. during the liquid- to gas-phase transition process. LC-MS ionisation processes involve either gas-phase ionisation (El), gas-phase chemical reactions (Cl, APCI) or ion evaporation (TSP, ESP, SSI). Van Baar [519] has reviewed ionisation methods (TSP, APCI, ESI and CF-FAB) in LC-MS. 

These problems have largely been solved by the development of a wide variety of powerful LC-MS interfaces (reviewed in Refs. [1-3]). In the following paragraphs, the two most widely used atmospheric pressure ionisation (API) systems, namely atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI), are briefly described, along with the older technique of thermospray ionisation... 

A considerable amount of information has been accumulated during the review period with respect to fragmentation studies of flavonoid aglycones and their glycosides using ionization techniques such as El and CID (Figure 2.17). Tandem mass spectrometry with soft ionization methods such as FAB, ESI, and APCI have been used for the structural characterization of a variety of flavonoids, and both deprotonation ° ° and... 

Unlike with GC-MS, quality criteria for identification of drug residues by LC-MS have not been yet defined within the European Union, but this is currently under review. Criteria for GC-MS stipulate the measurement of preferably at least four diagnostic ions. However, this is not always possible with LC-MS because most compounds will only produce an M ion in positive mode or a M ion in negative mode, with little fragmentation when using thermospray (TSP), electrospray (ESP), or atmospheric pressure chemical ionization (APCI). Even where the ions and ratios are in agreement, there will be still possibility of misidentification. For this reason, mass spectra data are often interpreted with additional supporting data such as the LC retention times, as, for example, in the LC-MS analysis of sulfadimethoxine and sulfadoxine that present identical mass spectra (24). 

The instrumentation and interfaces that had been used up to 1998 in CWC-related LC/MS analysis were summarized previously (4). At that time, sources that operate at atmospheric pressure, using electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI), were displacing their predecessors that used thermospray ionization or continuous flow fast atom bombardment. Atmospheric pressure ionization (API), either ESI or APCI, is now the method of choice in CWC-related analysis and will be the focus of this current review. A small number of recent applications involving alternative types of ionization are also included. For earlier applications of LC/MS to chemical weapons (CW) analysis, using thermospray and other ionization methods, the reader is referred to our previous review (4). The other major trend has been the increasing availability and ease of use of less-expensive bench-top quadrupole and... 

Although there is usually no need for any chemical derivatization, caution has to be applied when LC-MS/MS data are reviewed. The ionization of analytes might be affected and altered by endogenous compounds, which can be present in the matrix and which might coelute together with the analyte or internal standard. This can lead to ion suppression (predominantly observed with ESI ionization) as well as ion enhancement, which more often is observed when APCI-ionization is used. Matrix effects can lead to false results. 

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. 

Liquid chromatography-mass spectrometiy (LC-MS) based on atmospheric-pressure ionization (API) was demonstrated as early as 1974 (Ch. 3.2.1). However, it took until the late 1980 s before API was starting to be widely applied. Today, it can be considered by far the most important interfacing strategy in LC-MS. More than 99% of the LC-MS performed today is based on API interfacing. In this chapter, instrumentation for API interfacing is discussed. First, vacuum system for MS and LC-MS are briefly discussed. Subsequently, attention is paid to instrumental and practical aspects of electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), and other interfacing approaches based on API. The emphasis in the discussion is on commercially available systems and modifications thereof. Ionization phenomena and mechanisms are dealt with in a separate chapter (Ch. 6). Laser-based ionization for LC-MS is briefly reviewed (Ch. 5.9). 

Many papers on the LC-MS analysis of pesticides and related compounds deal with the characterization of interface and ionization performance, the improvement of detection limits by variation of experimental conditions, and the information content of the mass spectra. As far as ESI and APCI ate concerned, this type of information is reviewed for various pesticide classes in this section (see Ch. 4.7.4 for results with thermospray and Ch. 5.6.1 with particle-beam interfacing). 

Prior to the advent of electrospray ionization (ESI), the primary use of mass spectrometry in natural product discovery was the structural elucidation of compounds that had been isolated with bioassay-guided fractionation. With the advent of commercial ESI and atmospheric-pressure chemical ionization (APCI) sources in the early 1990s [74,75], researchers gained access to LC-MS instrumentation that could be used to directly analyze natural product mixtures. This allowed the integration of mass spectrometry into the earliest stages of natural product discovery. The impact of ESI and APCI on natural products discovery has been the subject of recent reviews [76,77]. 

One of the earliest reports of SFC interfaced with APCI was by Huang et al. [121]. The authors used a pin-hole restrictor to maintain supercritical fluid conditions in a packed-column (pcSFC) system. Results for a mixture of five corticosteoids were described with an injection of 25 ng of each of the components. The system was also amenable for capillary SFC/MS applications with minimum modification. Sadoun and Virelizier [122] reported an SFC interface with ESI in which a two-pump SFC and a packed column were used with the outlet directly interfaced to an ESI source of a quadrupole mass spectrometer. Also, 1-30% (v/v) of polar organic modifier (Me0H-H20 95 5) was added to CO2 mobile phase to help elute polar organic compounds. The setup was shown to allow analysis of polar organic compounds that were difficult to analyze with earlier implementations of SFC-MS with a chemical ionization interface. A recent review article is available on pcSFC-MS [123]. 

Mass spectrometry (MS) has become one of the most important analytical tools employed in the analysis of pharmaceuticals. This can most likely be attributed to the availability of new instrumentation and ionization techniques that can be used to help solve difficult bioanalytical problems associated with this field (1-8). Perhaps the best illustration of this occurrence is the development of electrospray (ESI) and related atmospheric-pressure ionization (API) techniques, ion-spray (nebulizer-assisted API), turbo ionspray (thermally assisted API), and atmospheric pressure chemical ionization (APCI nebulization coupled with corona discharge), for use in drug disposition studies. The terms ESI and ionspray tend to be used interchangeably in the literature. For the purpose of this review, the term API will be used to describe both ESI and ionspray. In recent years there has been an unprecedented explosion in the use of instrumentation dedicated to API/MS (4,6,8-14). API-based ionization techniques have now become the method of choice for the analysis of pharmaceuticals and their metabolites. This has made thermospray (TSP), the predominant LC/MS technique during the 1980s, obsolete (15). Numerous reports describing the utility of API/MS for pharmaceutical analysis have appeared in the literature over the last decade (7). The... 

The results of PAH analysis with different types of interfaces (e.g. ESI, APCI, PBI and TSP - were reported by Clench et al. reviewing the state of the art of various mass spectral techniques [28]. For more polar PAHs pneumatically assisted ESI-LC-MS was used to determine mixtures of hydroxy polycyclic aromatic hydrocarbons. The abundance of ions dependent on flow rates was shown. ESI inonization was found to be less sensitive compared to APCI ionisation [304]. PAH analysis with ESI-LC-MS combined with RP-LC with post-column addition of silver nitrate was applied for the determination of 10 PAHs in river water. PAHs resulted in [Mj and [M-i-Ag]. The detection limits of different PAHs in spiked samples ranged from 0.001 to 0.03 pg L [442]. 

Several review papers have reported on the application of ESI in the analysis of surfactants. Di Corcia reviewed LC-MS methods for the unequivocal identification of isomers, oligomers and homologues of the technical blends of surfactants and their biodegradation intermediates in environmental samples at trace levels with particular attention to ESI and TSP apphcations [40]. Qench et al. [28] described the applications of LC-MS in environmental analysis using the interfaces PBI, TSP, APCI and ESI in use or just coming into use in th early 1990s. 

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