Ionization methods thermospray

This method is still in use but is not described in this book because it has been superseded by more recent developments, such as particle beam and electrospray. These newer techniques have no moving parts, are quite robust, and can handle a wide variety of compound types. Chapters 8 through 13 describe these newer ionization techniques, including electrospray, atmospheric pressure ionization, plasmaspray, thermospray, dynamic fast-atom bombardment (FAB), and particle beam. 

Ionization methods that may be utihzed in LC-MS include electron ionization (El), chemical ionization (Cl), fast-atom bombardment (FAB), thermospray (TSP), electrospray (ESI) and atmospheric-pressure chemical ionization (APCI). 

For many years, electron ionization, then more usually known as electron impact, was the only ionization method used in analytical mass spectrometry and the spectra encountered showed exclusively the positively charged species produced during this process. Electron ionization also produces negatively charged ions although these are not usually of interest as they have almost no structural significance. Other ionization techniques, such as Cl, FAB, thermospray, electrospray and APCI, however, can be made to yield negative ions which are of analytical utility. 

The sensitivity of the interface is compound-dependent but generally high sensitivity is possible by using one of the ionization methods available (thermospray, filament and discharge). 

Electrospray ionization occurs by the same four steps as listed above for thermospray (see Section 4.6). In contrast to thermospray, and most other ionization methods nsed in mass spectrometry, it shonld be noted that electrospray ionization nnnsnally takes place at atmospheric pressure. A similar process carried out under vacuum is known as electrohydrodynamic ionization and gives rise to qnite different analytical results. This technique has not been developed into a commercial LC-MS interface and will not be considered further. 

The most recent progress in MS analysis of chlorophylls has been obtained with the development of atmospheric ionization methods such as atmospheric pressure chemical ionization (APCl) and electrospray ionization (ESI). These techniques have demonstrated much more sensitivity than thermospray ionization, detecting chloro-... 

Figure 6.10 Production of positive ions by thermospray ionisation. After Ashcroft [35]. From A.E. Ashcroft, Ionization Methods in Organic Mass Spectrometry, The Royal Society of Chemistry, Cambridge (1997). Reproduced by permission of The Royal Society of Chemistry...

Recent advances in electrospray ionization (ESI), atmospheric-pressure chemical ionization (APCI), thermospray, and particle beam LC-MS have advanced the analyst toward the universal HPLC detector, but price and complexity are still the primary stumbling blocks. Thus, HPLC-MS remains expensive and the technology has only recently been described. Early commercial LC-MS uses particle beam and thermospray sources, but ESI and APCI interfaces now dominate. Liquid chromatography MS can represent a fast and reliable method for structural analyses of nonvolatile compounds such as phenolic compounds (36,37), especially for low-molecular-weight plant phenolics (38), but the limited resolving power of LC hinders the widespread use of its application for phenolics as compared to GC-MS. 

Fig. 5 Statistical evaluation of LC-MS-based methods for tropane alkaloids referred in this chapter. (a) Relative frequency of ionization methods. +APCI positive atmospheric pressure chemical ionization, +ESI positive electrospray ionization, FAB fast atom bombardment, +TSP positive thermospray, (b) Relative frequency of scan modes used. MS full scan MS, MS/MS tandem mass spectrometry (product ion scan), MRM multiple reaction monitoring, SIM selected ion monitoring, (c) Relative frequency of mass analysers used. EBQtQ2 double focusing sector field mass spectrometer, IT ion trap, QqQ triple quadrupole, SQ single quadrupole. Considered publications were found by PubMed data-based search and references cited in these articles...

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... 

The optimal HPLC separation conditions for the nemadectins precluded the use of "buffer only" ionization. The Finnigan TSP-46 thermospray source is equipped with a filament and a discharge electrode as choices for an external ionization method. Both positive and negative ion detection are available. The best choice for an ionization method and for the mode of ion detection would have to provide adequate sensitivity for minor component analysis, unambiguous molecular weight information, and sufficient fragmentation to differentiate between components with similar retention times and identical molecular weights. 

Microdialysis coupled to mass spectrometry is a powerful technique for on-and off-line analysis, providing information on pharmacokinetics, drug transport, and metabolite formation. With the widespread availability of LC/ESI/MS instruments there has been a shift toward liquid chromatography and away from gas chromatography and flow injection. Electrospray is the ionization method of choice for most applications and tandem mass spectrometry has grown in popularity. Thermospray and cfFAB applications have been used with microdialysis, but are older, obsolete techniques. 

To perform mass spectrometry, one must make ions from neutral molecules. Ionization methods have advanced from the classic electron ionization (El), through chemical ionization, field desorption, fast atom bombardment (FAB), h 62 thermospray to the atmospheric pressure ionization (API) techniques currently favored. El is classic, but its is restricted to thermally stable, volatilizable compounds. Field desorption was always a specialized niche technique applicable to some larger compounds. Fast atom bombardment enjoyed a meteoric rise in use when it was first reported in 1981 but it has all but disappeared now, being replaced by the API tech-... 

Table (11) gives an overview on the LC-MS methods described in the literature. The vast majority of studies has been performed with the thermospray interface in the positive ionization mode. Thermospray detection is not very sensitive [279], For procyanidins a detection limit of 1 ig has been reported [269], No data are available on the detection limits of procyanidins using other types of interfaces. So far, LC-MS has not yet been applied to the quantitative analysis of procyanidins. 

MS is becoming the detection system of choice for LC by virtue of its flexibility and high selectivity for individual solutesHowever, LC-MS is always less sensitive than GC-MS as a result of the need to transfer the analytes from the liquid phase into a high-vacuum gas phase. Other limitations of LC-MS combination include the inability to use nonvolatile buffers, the narrow optimum range for eluent flow rate influence of the proportion of organic modifier on the sensitivity, and the narrow choice of ionization methods.Nevertheless, LC-MS has been widely accepted as an advantageous choice for the determination of carbamate pesticides in water matrices, which is more robust and flexible in the absence of derivatization. Thermospray and particle-beam interfaces are probably most commonly used for offline and online determination of carbamates in Atmospheric pressure sources such as... 

For the HPLC-MS systems, many different ionization techniques have been described in the past. Various interface, ionization methods, and operating techniques applicable to LC-MS are discussed in [117J for instance Thermospray, particle beam, electrospray (ES), field desorption (FD), fast atom bombardment (FAB), time of flight (TOF), etc. The electrospray technique produces a soft ionization for thermally labile compounds, while FAB has the advantage that higher molecular mass samples can be introduced into the mass spectrometer. Table 8 offers a rough guide to the applicability of various LC-MS interfaces. For more detailed information on LC-MS, see [118]. 

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