Ambient ionization methods

Ambient Ionization Methods and Their Early Applications in ADME Studies... 

Two Most Established Ambient Ionization Methods DESI and DART.378... 

Early Applications of Ambient Ionization Methods in ADME Studies.379... 

One of the most significant developments in mass spectrometry in the recent years is the introduction of a new class of ionization methods where samples in either solid or liquid state can be directly ionized in their native environment under ambient conditions (rather than inside a mass spectrometer) without any sample preparation. This new class of ionization methods is often referred to as ambient ionization methods [1,2], Because these methods generally ionize analytes on the surface or near the surface of the samples at atmospheric pressure, they have also been called atmospheric pressure surface sampling/ionization methods or direct/open air ionization methods [3], Since the first reports on ambient ionization with desorption electrospray ionization (DESI) [4] and direct analysis in real time (DART) [5], numerous reports have been published on the applications of these new ionization methods as well as the introduction of many related ambient ionization methods such as desorption atmospheric pressure chemical ionization (DAPCI) [6], atmospheric solid analysis probe (ASAP) [7], and electrospray-assisted laser desorption/ionization (ELDI) [8], Recently, two reviews of the various established and emerging ambient ionization methods have been published [2,3],... 

In this chapter, we first provide an introduction to DESI and DART as the two most established ambient ionization methods. We then review some details on the early applications of DESI and DART in ADME studies. We close this chapter with some perspectives on the future role of ambient ionization methods in ADME studies. 

TWO MOST ESTABLISHED AMBIENT IONIZATION METHODS DESI AND DART... 

Shortly after the report on the DESI technique, DART was reported as another ambient ionization method [5], In this method, a gas with a high ionization potential such as helium or nitrogen flows through a probe that contains multiple chambers. The gas first flows into a discharge chamber where electrical discharge occurs by applying a potential of several thousand volts across a cathode and an anode. The... 

EARLY APPLICATIONS OF AMBIENT IONIZATION METHODS IN ADME STUDIES... 

Although still at a very early stage, ambient ionization methods, mostly DESI and DART, have been evaluated and used in the ADME studies for drug candidates. The fact that ambient ionization methods can analyze samples without sample preparation seems extremely attractive for bioanalysis as sample preparation is widely considered as the key bottleneck in bioanalysis. Also, the fact that samples can be analyzed... 

Matrix effects are another key aspect that needs to be carefully considered for quantitative applications with ambient ionization methods. Currently an extensive comparison of the matrix effects among various ambient mass spectrometric methods is not available. DESI has been evaluated for salt tolerance, and it was found that DESI is more tolerant of the presence of salts than is electrospray [28], On the other... 

In addition to some early applications in bioanalysis, ambient ionization mass spectrometry has been used as an imaging tool to study drug distribution in tissue sections. Most of the work reported so far involved the use of DESI as the ambient ionization method. Compared to other mass spectrometry-based tissue imaging techniques such as MALDI and SIMS, DESI allows tissue samples to be analyzed under ambient conditions without sample preparation, which simplifies the procedure and prevents the redistribution of analytes during matrix deposition. A major drawback of DESI as an imaging tool is its relatively low spatial resolution (typically 250 pm) and therefore cannot be used for cellular or subcellular imaging. 

Overall, ambient ionization methods have showed to be a highly promising tool for ADME studies. Although most of the early work to date has been focused on the throughput advantage, the future role of ambient ionization methods in the pharmaceutical industry and particularly for the ADME studies will largely depend on how their unique features can be utilized to solve problems that are not readily solvable with conventional LC-MS/MS methods. 

Methods Ambient ionization methods, of which there are now over 20, e.g., desorption electrospray ionization (DESI), desorption atmospheric pressure chemical ionization (DAPC), desorption atmospheric pressme photo-ionization (DAPPI), and direct analysis in real time (DART), are now joined by paper spray, a method where ESI is initiated at the pointed tip of a piece of filter paper. A drop of blood ( 15 pi) is dried on the paper, and then the paper is moistened with 25 pi of a solvent suited to both the extraction of the analytes from the blood and the ESI process (e.g., 90% methanol 10% water with either 100 ppm acetic acid or 200 ppm sodium acetate). When the paper is exposed to high voltage (3-5 kV) while held close ( 5 mm) to the entrance of the mass analyzer, a spray (similar to electrospray) is induced at the tip of the paper as capillary action carries extracted compounds through the paper (Figure 4.5). The spray is maintained for 30-90 s at a flow rate comparable to that used in nano-electrospray. 

Ifa, D.R., Wu, C., Ouyang, Z., Cooks, R.G. (2010) Desorption Electrospray Ionization and Other Ambient Ionization Methods Current Progress and Preview. Analyst 135 669-681. 

Ambient MS is another advance in the field. It allows the analysis of samples with little or no sample preparation. Following the introduction of desorption electrospray ionization (DESI) [108,109], direct analysis in real time (DART) [110], and desorption atmospheric pressure chemical ionization (DAPCI) [111, 112], a number of ambient ionization methods have been introduced. They include electrospray-assisted laser desorption/ionization (ELDI) [113], matrix-assisted laser desorption electrospray ionization (MALDESI) [114], atmospheric solids analysis probe (ASAP) [115], jet desorption ionization (JeDI) [116], desorption sonic spray ionization (DeSSI) [117], field-induced droplet ionization (FIDI) [118], desorption atmospheric pressure photoionization (DAPPI) [119], plasma-assisted desorption ionization (PADI) [120], dielectric barrier discharge ionization (DBDI) [121], and the liquid microjunction surface sampling probe method (LMJ-SSP) [122], etc. All these techniques have shown that ambient MS can be used as a rapid tool to provide efficient desorption and ionization and hence to allow mass spectrometric characterization of target compounds. 

Figure F.l. Ambient ionization methods for ionizing condensed phase samples on surfaces using droplets, atom beams, electrical discharges and laser beams. For comparison, some vacuum methods are also shown.

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