Other Ionization Methods

Methods other than electron bombardment (EI-MS) can be used to obtain mass spectral data. In chemical ionization-mass spectrometry (CI-MS), the sample is sprayed with a pre-ionized gas such as methane or ammonia that causes the sample to ionize by electron transfer or proton transfer from the gas to the sample. Because the molecular ions produced by this technique are less apt to undergo fragmentation, the ability to obtain the molecular mass (and therefore the molecular formula) of the sample is enhanced. 

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In contrast to most other ionization methods, the majority of ions produced by electrospray are multiply charged. This is of great significance as the mass spectrometer measures the m/z (mass-to-charge) ratio of an ion and the mass range of an instrument may therefore be effectively extended by a factor equivalent to the number of charges residing on the analyte molecule, i.e. an ion of m/z 1000 with... 

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. 

Electrospray ionization, in contrast to the majority of other ionization methods employed in mass spectrometry, produces predominantly multiply charged ions of the intact solute molecule. This effectively extends the mass range of the mass spectrometer and allows the study of molecules with molecular weights well outside its normal range. 

MALDI generated a great demand for a mass analyzer ideally suited to be used in conjunction with a pulsed ion source and capable of transmitting ions of extremely high mass up to several 10 u. [24] Since then, the performance of TOF instruments has tremendously increased. [25,26] TOF analyzers were adapted for use with other ionization methods and are now even strong competitors to the well-established magnetic sector instruments in many applications. [25,27]... 

In principle, any other ionization method can be combined with a TOF analyzer even if it is not an intrinsically pulsed technique, provided there are means to extract ions in a pulsed manner from such an ion source (Chap. 4.2.6). 

Note Sample introduction systems such as reservoir inlets, chromatographs, and various types of direct probes (Chap. 5.3) are of equal importance to other ionization methods. The same holds valid for the concepts of sensitivity, detection limit, and signal-to-noise ratio (Chap. 5.2.4) and finally to all sorts of ion chromatograms (Chap. 5.4). 

According to the above definition, sensitivity does not only depend on the ionization efficiency of El or any other ionization method. Also relevant are the extraction of ions from the ion source, the mass range acquired during the experiment, and the transmission of the mass analyzer. Therefore, the complete experimental conditions have to be stated with sensitivity data. 

There is - as with any other ionization method - no strict upper limit for molecular mass, nevertheless a range of up to 800-1000 u is a realistic estimate. Exceptions up to 1300 u are observed, if the analyte is extremely unpolar, e.g., from numerous fluoroalkyl or trialkylsilyl groups which also significantly contribute to molecular mass. 

Similar procedures are necessary when other ionization methods are applied to this compound class. 

The significant enhancement of ion formation by a corona discharge as compared to a Ni source has already been implemented in early API sources. [139,140] The nature of the APCI plasma varies widely as both solvent and nebulizing gas contribute to the composition of the Cl plasma, i.e., APCI spectra can resemble PICI, CECI, NICI, or EC spectra (Chap. 7.2-7.4) depending on the actual conditions and ion polarity. This explains why APCI conditions suffer from comparatively low reproducibility as compared to other ionization methods. 

Favaro, S. Pandolfo, L. Traldi, P. The Behavior of [Pt(r LAllyl)XP(C6H5)3] Complexes in ESI Conditions Compared With Those Achieved by Other Ionization Methods. Rapid Commun. Mass Spectrom. 1997,11, 1859-1866. 

If no other ionization method is available, how could the extent of fragmentation be decreased in EI ... 

To many, mass spectrometry is synonymous with El mass spectrometry. This view is understandable for two reasons. First, historically, El was universally available before other ionization methods were developed. Much of the early work was El mass spectrometry. Second, the major libraries and databases of mass spectral data, which are relied upon so heavily and cited so often, are of El mass spectra. Some of the readily accesible databases contain El mass spectra of over 390,000 compounds and they are easily searched by efficient computer algorithms. The uniqueness of the El mass spectrum for a given organic compound, even for stereoisomers, is an almost certainty. This uniqueness, coupled with the great sensitivity of the method, is... 

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... 

While El does not imply any ion-molecule reactions, the latter provide the whole basis of Cl and of all the API methods. Other ionization methods give rise to ion-molecule reactions as secondary processes. We will now emphasize some characteristics of these gas-phase reactions and compare them with condensed-phase reactions. 

We saw that numerous ionization techniques exist that yield radical cations or radical anions, protonated or deprotonated molecules, and various adducts. These ions yield fragments with an even number of electrons (closed shell) or with an odd number of electrons (open shell). Even though the radical cations derived from electron ionization sources retain a privileged status in common mass spectrometry, the other ionization methods become increasingly common. Electron ionization is not possible for many categories of molecules. Therefore, we will not limit the discussion to radical cations. 

In a recently published book [1280] on mass spectrometry, the fragmentation of organic molecules under electron impact, electron capture, and other ionization methods is described not in the traditional way - by classes - but rather by isomerization and fragmentation types with simple bond cleavage, hydrogen- and skeletal rearrangements with systematic thermodynamic approach and separately for positive and negative ions. Our review on mass spectrometry of nitroazoles has been reported in 1998 [1281],... 

The MBl was widely used in LC-MS applications between 1978 and 1990. The most important reasons for its success are the compatibility with a broad range of chromatographic conditions, while next to El and chemical ionization (Cl) other ionization methods, especially fast-atom bombardment (FAB) [23-24], can be employed as well. 

Other ionization methods have been employed, including field ionization. McReynolds and Anbar [244a,b] developed a very sensitive FI source. 

The MALDI data originate from a series of physical phenomena and chemical interactions originating from the parameterization (matrix nature, analyte nature, matrix/analyte molar ratio, laser irradiation value, averaging of different single spectra), which must be kept under control as much as possible. However, the results obtained by MALDI are of great interest, due to its applicability in fields not covered by other ionization methods. Due to the pulsed nature of ionization... 

Favaro, S., Pandolfo, L., and Traldi, P. (1997). The behaviour of [Pt (rf-allyl) XP (C6H5)3] complexes in electrospray ionization conditions compared with those achieved by other ionization methods, Rapid Commun. Mass Spectrom., 11,1859-1866. 

In contrast to protonated primary, secondary and tertiary amines, tetraalkyl ammonium ions, R4N+, obviously cannot be produced by protonation of the parent amine. In principle, however, these species may be made by alkyl cationation of the amine. In practice, other ionization methods are usually employed to form the gaseous ions from the appropriate salts. Thus, fast atom bombardment (FAB) of a solution of tetraalkylammonium bromides in a glycerol matrix is a convenient means of geuCTating the free tetraalkylammonium ion in the gas phase. A modified procedure, in which an amine is dissolved in thioglycerol/2,2 -dithioethanol matrix saturated with oxalic acid, allows RNH3+, R2NH2" and R3NH+ ions to be produced under closely similar conditions. ... 

In more complex or less well-characterized systems, the FI/FD molecular weights alone may not be sufficient to elucidate the proper chemical structures. In these cases, the FI/FD results can suggest appropriate methods (spectroscopic and/or chromatographic) for further study. For example, other ionization methods can be used to obtain additional mass spectra. Tandem mass spectrometry (MS/MS) can be used to obtain fragmentation patterns, and high resolution accurate mass measurements can be used to obtain atomic compositions (AC-MS) for various components. 

There are few reports in fhe liferafure of FD being used as the ion source in tandem (MS/MS) experimenfs. The relatively weak ion currents and transient signals make FD-MS/MS spectra (as one paper has put it) "technically challenging to obtain."" Most analysts, it would seem, obtain "survey" spectra by FD-MS for screening purposes. Then if more information is needed, MS/ MS experiments are performed using other ionization methods (e.g., El, Cl, FAB). In our experience it is almost always preferable to do MS/MS with ionization methods other than FI or FD. Thus the FD-MS/MS data that do appear in the literature seem to have been obtained, for the most part, for demonstration purposes. 

FI-MS and FD-MS are only used in a handful of laboratories worldwide. Those of us who have used the methods for several years still rely upon them heavily. Despite the large number of other ionization methods that have become available, it is clear that FI-MS and FD-MS shll possess some capabilities that have not been duplicated by newer methods. In particular. 

Although most lipidomic studies are conducted using ESI, other ionizations methods can also be used. Schiller et al. have recently reviewed the... 

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