Atmospheric-pressure desorption ionization techniques

Desorption electrospray ionization (DESI) may serve as an example of the maiy atmospheric-pressure surface ionization technique that has recently been introduced [63, 76]. In DESI, the high-velocity spray of charged microdroplets from a (pneumatically assisted) electrospray needle is directed at a surface, which is mounted in front of the ion-sampling orifice of an API source (see Fig. 7.6). Surface constituents are released fiom the surface and ionized. These gas-phase ions can be introduced to and observed by MS [77]. In this way, DESI-MS enables for instance the analysis of dmgs in tablets or natural products in plant parts withont extensive sample pre-treatment or prior separation. In addition, DESI-MS and some of its related snrface ionization techniqnes enable chemical imaging of surfaces such as thin-layer chromatography (TLC) plates and tissue sections [78]. 

In addition to DESI and AP-MALDI, a large variety of other, sometimes closely related, atmospheric-pressure desorption ionization techniques have been introduced in the past decade, connected to a huge number of acronyms. Van Beikel et al. [76] tried to classify these emerging techniques into four categories, i.e., (1) thermal desorption ionization, (2) laser desorption/ablation ionization, (3) liquid-jet and gas-jet desorption ionization, and (4) hquid extraction surface sampling probe ionization. 

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Traditionally, products and adsorbates had to be volatile enough so that they could be carried from the cell into the mass spectrometer, either by headspace sampling, or, more commonly for near-simultaneous analysis (referred to as differential electrochemical mass spectrometry), across a nanoporous, gas-permeable membrane (e.g., Teflon) supported at the tip of a microcapillary placed close to the electrode. Alternatively, a Pt-coated membrane electrode can be used. But the advent of the so-called soft atmospheric pressure desorption/ionization techniques associated with liquid chromatography-mass spectrometry has allowed the sampling of the solvent and involatile solutes directly. The spectra are more... 

A turning point in atmospheric pressure desorption-ionization techniques for the analysis of chemical compounds was reached very recently with the introduction of DESI (U.S. Patent Application 20050230635). In this approach, charged droplets from an electrosprayed solution are directed toward a solid sample by means of a high-velocity gas stream. The charged droplets ablate the exterior of the sample, removing and ionizing chemical compounds present on the surface. Accordingly, DESI permits the direct analysis of condensed-phase samples with minimal or no sample preparation. 

From the time of the second edition published in 2001 until now, much progress has been achieved. Several techniques have been improved, others have almost disappeared. New atmospheric pressure desorption ionization sources have been discovered and made available commercially. One completely new instrument, the orbitrap, based on a new mass analyser, has been developed and is now also available commercially. Improved accuracy in low-mass determination, even at low resolution, improvements in sensitivity, better detection limits and more efficient tandem mass spectrometry even on high-molecular-mass compounds are some of the main achievements. We have done our best to include them is this new edition. 

Direct analysis of solid samples or analytes present on solid or liquid surfaces without any sample preparation has recently gained much interest. Desorption electrospray ionization (DESI) is an atmospheric pressure desorption ionization method introduced by Cooks et al. (2006) where ions are produced directly from the surface to be analyzed. The DESI technique features the use of charged liquid droplets that are directed by a high velocity as jet (on the order of 300 m/s) to the surface to be analyzed. Analytes are desorbed from the surface and analyzed by the mass spectrometer. 

Electrospray ionization [21] is one of the most widely utilized ionization techniques employed today for the analysis of thermally fragile molecules. As such, it has assumed an important role in the analysis of biologically important molecules. ESI is a desorption ionization technique. This means that ions are formed before or during the transition from the liquid phase and need not be volatilized in advance of the ionization event (as is the case for El, Cl, etc.). Like APCI and APPI, ESI occurs at atmospheric pressure outside the vacuum chamber of the mass spectrometer (Fig. 11.5). A solution of the analyte passes through... 

Figure A.3A.1 Flow chart illustrating the selection of a suitable ionization technique for the mass spectrometric analysis of a sample. Abbreviations APCI, atmospheric pressure chemical ionization Cl, chemical ionization El, electron impact FAB, fast atom bombardment MALDI, matrix-assisted laser desorption/ionization.

Strege summarized the technique of high-performance liquid chromatography-electrospray ionization mass spectrometry (HPLC-ESI-MS) in dereplication of natural products. In contrast to earlier electron impact ionization (El), ESI technique is applicable to virtually any ion in solution with a soft ionization process. A comparison of ESI with fast atom bombardment (FAB), matrix assisted laser desorption ionization (MALDI), atmospheric pressure chemical ionization (APCI) and other techniques demonstrates its superior sensitivity, compatibility and reliability when coupled with HPLC [51]. 

An ideal interface should not cause extra-column peak broadening. Historical interfaces include the moving belt and the thermospray. Common interfaces are electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCl). Several special interfaces include the particle beam—a pioneering technique that is still used because it is the only one that can provide electron ionization mass spectra. Others are continuous fiow fast atom bombardment (CF-FAB), atmospheric pressure photon ionization (APPI), and matrix-assisted laser desorption ionization (M ALDl). The two most common interfaces, ESI and APCI, were discovered in the late 1980s and involve an atmospheric pressure ionization (API) step. Both are soft ionization techniques that cause little or no fragmentation hence a fingerprint for qualitative identification is usually not apparent. 

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. 

Identification of the forms thus obtained using complementary molecule-specific techniques (nuclear magnetic resonance infrared [IR] matrix-assisted laser desorption/ionization electrospray ionization [ESl]/atmospheric pressure chemical ionization mass spectrometry [MS])... 

The dynamic development of mass spectrometry has had a huge impact on lipid analysis. Currently, a variety of suitable mass spectrometers is available. In principal, a mass spectrometer consists of an ion source, a mass analyzer, and an ion detector. The typical features of each instrument (Fig. 2) result mostly from the types of ion source and mass analyzer. To date, the ionization techniques apphed to lipid analysis include Electrospray Ionization (ESI or nano-ESI), Atmospheric Pressure Chemical Ionization (APCI), Matrix-Assisted Laser Desorption/Ionization... 

A variety of MS formats are widely accepted and applied in the pharmaceutical industry. The specific MS application is often defined by the sample introduction technique. The pharmaceutical applications highlighted in this article feature two types of sample introduction techniques dynamic and static. Dynamic sample introduction involves the use of high-performance liquid chromatography (HPLC) on-line with MS. The resulting liquid chromatography/mass spectrometry (LC/MS) format provides unique and enabling capabilities for pharmaceutical analysis. The electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI) modes are the most widely used. Static sample introduction techniques primarily use matrix-assisted laser desorption/ionization (MALDI). ... 

Three popular ionization techniques are electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI) and matrix-assisted laser desorption (MALDI). Electrospray is the most widely used ionization technique when performing LC-MS, and has proved to be a most versatile tool for soft ionization [72] of a large variety of analytes such as them described in paper I. Figure 6 shows the principle of the ESI. 

Nearly all known ionization methods of mass spectrometry (including electron impact, laser desorption and fast atom bombardment) were already successfully applied to lipids. However, many ionization techniques are not very suitable for the analysis of complex PL mixtures as they provide considerable amounts of fragment ions. Therefore, only three soft-ionization methods play nowadays a major role in lipid analysis. Beside atmospheric pressure chemical ionization (APCI) (Byrdwell 2001), electrospray ionization (ESI) (Pulfer and Murphy... 

A new generation of mass spectrometer inlets allow for direct sampling of a substrate under ambient conditions. Theoretically, this eliminates the need for any sample preparation. Examples include direct analysis in real time (DART) and desorption electrospray ionization (DESI), as well as desorption atmospheric-pressure chemical ionization (DAPCI) and atmospheric solids analysis probe (ASAP). These techniques utilize a source of energy interacting directly with a sample surface at ambient pressure, causing molecules of interest to desorb, ionize, and be sampled by a mass spectrometer. 

Thome FA, Heavner DL, Ingebrethsen BJ, Eudy LW, Green CR (1986) Environmental tobacco smoke monitoring with an atmospheric pressure chemical ionization mass spectrometer/mass spectrometer coupled to a test chamber. Proc 79th Annual Meet Air Pollution Control Assoc. Air Pollution Control Assoc, Pittsburgh, paper 86-37.6 Thompson CV, Jenkins RA, Higgins CE (1989) A thermal desorption method for the determination of nicotine in indoor environments. Environ Sci Technol 23 429-435 Thomson BA, Davidson WR, Lovett AM (1980) Applications of a versatile technique for trace analysis atmospheric pressure negative chemical ionization. Environ Health Perspect 36 77-84... 

Ions can be formed within the vacuum chamber of the mass spectrometer or outside the instrument at atmospheric pressure. Examples of in vacuo ionization are electron ionization (El), chemical ionization (Cl), and matrix-assisted laser desorption/ion-ization (MALDI). Ionization techniques carried out outside the vacuum system are collectively termed atmospheric pressure ionization (API). The most important API methods are electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). Among other API techniques are atmospheric pressure photo-ionization... 

Several other ionization methods have been developed based on DESI, including desorption atmospheric pressure chemical ionization (DAPCI), desorption atmospheric pressure photo-ionization (DAPPI), laser ablation electrospray ionization (LAESI), and extractive electrospray ionization (EESI). Each technique uses variations of the solvent, how the charged beam is formed, and how the beam is nsed to facilitate the prodnction of analyte ions. Because these are surface methods (except EESI), they are incompatible with LC. 

El and Cl methods can be used if the compound to be studied is sufficiently volatile and stable to be vaporized intact. However, only 20% of the organics found in surface water are volatile enough to be amenable to GC-EI-MS or GC-CI-MS. Today, there are a variety of other ionization techniques available electrospray ionization (ESI), atmospheric pressure chemical ionization, matrix-assisted laser desorption ionization, and fast atom bombardment. Each of these has its advantages and disadvantages. A simple guideline to the most likely optimum ionization technique for a given class of substance is given in Table 1. 

Suppression of ionization efficiency is important when the total ionizing capability of the ionization technique is limited, so that there is a competition for ionization among compounds that are present in the ion source simultaneously. In principle such a saturation effect must be operative for all ionization techniques, but in practice it is most important for electrospray ionization (Section 5.3.6), slightly less important for atmospheric pressure chemical ionization (Section 5.3.4), atmospheric pressure photoionization (Section 5.3.5) and matrix assisted laser desorption ionization (Section 5.2.2) it does not appear to be problematic under commonly used conditions for electron ionization and chemical ionization (Section 5.2.1) or thermospray (Section 5.3.2). Enhancement of ionization efficiency for an analyte by a co-eluting compound is less commonly observed and is, in general, not well understood. 

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