Spray-ionization techniques

Soft ionization methods can be classified into different groups (a) those occurring in the gas phase (b) spray ionization techniques (c) desorption ionization techniques. 

The ionization techniques described above occur in ion sources that are maintained under high vacuum. In contrast, spray ionization techniques operate at atmospheric pressure a solution spraying from a capillary is ionized at atmospheric pressure and the ions produced are driven into the high vacuum of the mass analyzer where they are separated. The use of spray and desorption ionizations does not require volatilization of the sample before ionization. This means that all these techniques can ionize nonvolatile, polar and large to very large compounds. 

An additional dimension to library analysis is introduced when mass spectrometry is coupled with common separation techniques, for example liquid chromatography (LC) and capillary electrophoresis (CE). While these couplings are compatible with spray ionization techniques such as ESI or APCI, they more or less exclude the use of the MALDI technique. Several contributions deal with LC-ES-MS [36, 37] and CE-ES-MS-coupling [38], For molecules with isobaric nominal masses, MS/MS-experiments are performed to confirm the identity of a library component. Separation and analysis of compound mixtures may also be performed by GC-MS [39, 40], As a supplement to the more common-... 

Desorption/Ionization Methods for Nonvolatile Materials In addition to the aforementioned ionization methods, the nonvolatile or thermally unstable compounds can be desorbed into the gas phase by fast atom bombardment (FAB), field desorption (FD), or spray ionization techniques. 

Coran, S. A., M. Bambagiotti-Alberti, V. Giannellini, G. Moneti, G. Pieraccini, A. Raffaelli, Continuous flow FAB and ion spray ionization techniques for the simultaneous determination of alkyltrimethylammonium surfactants by MS, Rapid Commun. Mass Spectrom., 1998, /2, 281-284. 

Factors may be classified as quantitative when they take particular values, e.g. concentration or temperature, or qualitative when their presence or absence is of interest. As mentioned previously, for an LC-MS experiment the factors could include the composition of the mobile phase employed, its pH and flow rate [3], the nature and concentration of any mobile-phase additive, e.g. buffer or ion-pair reagent, the make-up of the solution in which the sample is injected [4], the ionization technique, spray voltage for electrospray, nebulizer temperature for APCI, nebulizing gas pressure, mass spectrometer source temperature, cone voltage in the mass spectrometer source, and the nature and pressure of gas in the collision cell if MS-MS is employed. For quantification, the assessment of results is likely to be on the basis of the selectivity and sensitivity of the analysis, i.e. the chromatographic separation and the maximum production of molecular species or product ions if MS-MS is employed. 

A detailed description of sources used in atmospheric pressure ionization by electrospray or chemical ionization has been compiled.2 Atmospheric pressure has been used in a wide array of applications with electron impact, chemical ionization, pressure spray ionization (ionization when the electrode is below the threshold for corona discharge), electrospray ionization, and sonic spray ionization.3 Interferences potentially include overlap of ions of about the same mass-charge ratio, mobile-phase components, formation of adducts such as alkali metal ions, and suppression of ionization by substances more easily ionized than the analyte.4 A number of applications of mass spectroscopy are given in subsequent chapters. However, this section will serve as a brief synopsis, focusing on key techniques. 

The real breakthrough in LC/MS development was achieved with the broad introduction in the 1990s of atmospheric pressure ionization (API) techniques, such as electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), which enable the analysis of a wide variety of molecular species. The spectrum of available API techniques has been amended meanwhile by the introduction of sonic spray ionization (SSI) and atmospheric pressure photoionization (APPI). 

In ESI MS, a dissolved sample is sprayed through a capillary in an electric field which is situated in front of the vacuum inlet of the mass spectrometer [2]. Thus, in contrast to most other ionization techniques performed in high vacuum, the ionizahon process takes place at the atmospheric pressure. After leaving the capillary, the solvent forms a so-called Taylor-cone, which further forms a filament and finally, the spray of small droplets (Figure 14.2). These droplets carry charges on the surface this is frequently supported by the acidification of the solvent. The droplets shrink is caused by the evaporation of the solvent. This leads to an increase of the charge-per-surface ratio, finally... 

ESI tandem MS stands for electro spray ionization mass spectrometry performed in multistage. This technique is conducted based on the production of multiply charged ions from proteins and peptides. In this technique, ionization procedure is carried out within the instrument. Three types of mass analyzers are used individually or in combination. 

Most mass spectrometers equipped for electrospray ionization can be converted to APCI, and many commercial LC-APCI-MS instruments are equipped with both ionization techniques. During APCI, ionization takes place in an atmospheric pressure chamber when the sample molecules collide with solvent ions formed in a continuous corona discharge. Unlike electrospray, the needle used to spray the HPLC effluent is not at high voltage. 

Mass spectrometry (MS) is a very sensitive method of determining the mass of native proteins, as well as their purity. The two most common techniques are ESI-MS (electron spray ionization-MS) and MALDI-TOF-MS (matrix-assisted laser... 

The stoichiometry of the extracted M(III) complexes differs from that of the above-mentioned BTP ligands in that M L2 complexes (instead of M L3 complexes) have been identified by various techniques (e.g., X-ray crystallography, nuclear magnetic resonance, electro-spray ionization mass-spectrometry, and slope analysis in liquid-liquid extraction). 

Theory of CEC and methodological aspects of the technique are described exhaustively in the literature [1,2,3,4,5] and in this monograph and will not be dealt with here further. In this chapter, the current status of instrumentation for CEC is reviewed. General requirements, solvent delivery, and detection will be dealt with in some detail. Coupling of CEC separation with electro-spray ionization mass spectrometry (ESI MS) is of particular importance and is treated in a separate chapter of this monograph. 

Electrospray ionization is classihed as a soft ionization technique. It produces molecular-weight information and very little, if any, fragmentation of the analyte ion, unless induced in the vacuum region of the mass analyzer. The number of charges accumulated by an analyte ion is proportional to its number of basic or acidic sites. The spray polarity and conditions, solution pH and nature, as well as solute concentration will all effect the charge state distribution observed in the mass spectrum. Multiple charging of an analyte ion en-... 

Several ionization methods have been applied for CE-MS couphng. Matrix-assisted laser desorption ionization (MALDI), continuous flow fast atom bombardment (FAB), laser vaporization ionization with UV laser, sonic spray ionization and electrospray ionization (ESI) have all been used for coupling CE to MS. However, ESI is now undoubtedly the most widely used ionization technique, employing numerous analyzers including quadrupoles, magnetic sector, Fourier transform ion cyclotron resonance, time-offlight and trapping devices. However, quad-rupole detectors have predominantly been applied in CE-MS [6-8]. 

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... 

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