Development of ESI and Related Methods

ESI in its current state-of-the-art has not resulted from a straightforward development. It has many predecessors, some of which having been successful at their time, while others were rather short-lived methods replaced as soon as more sensitive or more robust techniques appeared [28]. Nonetheless, the development of all those techniques aimed at both the direct coupling of liquid chromatography to mass spectrometry and the access to highly polar or even ionic analytes. 

Following this historical sketch of milestones along the way to ESI, the below sections will emphasize the construction of ESI interfaces, the process of electrospray as such, and the pathways of ion liberation from the liquid phase into the state of isolated gas phase ions. 

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As mentioned above in the context of the analysis of hgnin degradation products, gas chro-matography/mass spectrometry and related methods have been developed as extremely powerful tools for the identification of phenolic compounds. Use of high-pressure liquid chromatography in combination with mass spectrometry adds to the analytical arsenal with respect to the detection of polar, non-volatile compounds but, in particular, the advent of modem ionization techniques, such as ESI and MALDI mass spectrometry, have continued to broaden the analytically governable field of organic chemistry. The latter methods diminish the need of derivatization of polar phenolics to increase the volatility of the analyte. In this section, a more or less arbitrary selection of examples for the application of mass spectrometric techniques in analytical chemistry is added to the cases already discussed above in the context of gas-phase ion chemistry. 

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... 

Different developed analytical method are discussed in this chapter related to the determination of illicit substances in blood (either whole blood, plasma, or serum), OF, urine, and hair. These methods take into consideration the particular chemical and physical composition of the matrix and applies each time a suitable pretreatment to remove interfering and matrix effect, to maximize recoveries and to achieve a suitable enrichment if necessary. For liquid matrices the applications of the most common techniques are considered from simple PPT to SPE and LLE the results of recent works from literature are reported and new trends as online SPE, pSPE, automated LLE (SLE) or MAE are examined. Several stationary phases have been shown to be suitable for determination of illicit drugs Cl8, pentafluorophenyl, strong cation-exchange, and HILIC columns. The trend toward fast chromatography is investigated, both UHPLC and HPLC with appropriate arrangements moreover, results obtained with different ion sources, ESI, A PCI, and APPI are compared. 

This chapter has discussed the applications of MALDI and ESI techniques for lipid analyses for both structural characterization and quantitation. In particular, the methodologies that are currently available for quantitation of individual lipid molecular species based on both ESI/MS and MALDI/MS are discussed in some detail. The limitations associated with each method and the potential concerns related to accurate quantitation of lipids have also been addressed. Overall, ESI/MS is the principal modality for global lipid identification and quantitation at the present time MALDI/MS can be selected as a primary screening technique before conducting large-scale lipid analyses and future technological developments may contribute to its enhanced usage. Therefore, a combination of both techniques will dramatically accelerate the development of lipidomics. 

The problems related to the nature of the analytes appeared most difficult in the early years of LC-MS, but meanwhile a variety of so-called soft-ionization techniques have been developed, sometimes as a spin-off or in conjunction with LC-MS developments. Electrospray ionization (ESI) is by far the most successful of these techniques. They allow the mass spectrometric analysis of highly polar, ionic, and (thermo)labile compounds. As a result, the problem can be considered to be solved. In the majority of the liquid-based soft-ionization methods, the analytes, either as neutrals or as preformed ions in solutions, are transferred to the gas phase by nebulization of the liquid and subsequent desolvation of the droplets. In this way, the amount of heat required in the transfer has been minimized, which is favorable for the type of compounds to be analyzed. 

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