Ionization methods, mass atmospheric pressure

The development of mass spectrometric ionization methods at atmospheric pressures (API), such as the atmospheric pressure chemical ionization (APCI)99 and the electrospray ionization mass spectrometry (ESI-MS)100 has made it possible to study liquid-phase solutions by mass spectrometry. Electrospray ionization mass spectrometry coupled to a micro-reactor was used to investigate radical cation chain reaction is solution101. The tris (p-bromophenyl)aminium hexachloro antimonate mediated [2 + 2] cycloaddition of trans-anethole to give l,2-bis(4-methoxyphenyl)-3,4-dimethylcyclobutane was investigated and the transient intermediates 9 + and 10 + were detected and characterized directly in the reacting solution. However, steady state conditions are necessary for the detection of reactive intermediates and therefore it is crucial that the reaction must not be complete at the moment of electrospray ionization to be able to detect the intermediates. 

Hirabayashi, A. Sakairi, M. Koizumi, H. Sonic spray ionization method for atmospheric-pressure ionization mass-spectrometry. Anal. Chem. 1994,66,4557-4559. 

See also Atomic Mass Spectrometry Inductively Coupled Plasma Laser Microprobe. Gas Chromatography Mass Spectrometry. Liquid Chromatography Liquid Chromatography-Mass Spectrometry. Mass Spectrometry Ionization Methods Overview Atmospheric Pressure Ionization Techniques Electrospray Liquid Secondary Ion Mass Spectrometry Matrix-Assisted Laser Desorption/ionization. Surface Analysis Secondary Ion Mass Spectrometry of Polymers Laser Ionization. 

In the last decade, mass spectrometry has developed at a tremendous rate. This expansion has been driven by the growing knowledge of ionization methods at atmospheric pressure (API), mainly electrospray ionization (ESI) [1], which makes the investigation of liquid solutions possible by mass spectrometry. ESI is used for ionic species in solution, and this ionization method opened up the access to the direct investigation of chemical reactions in solution via mass spectrometry. In principle, ESI make possible the detection and study not only of reaction substrates and products, but even short-lived reaction intermediates as they are present in solution, providing new insights into the mechanism of several studied reactions. 

It might be noted at this stage that some mass spectrometer inlets are also ionization sources. For example, with electrospray ionization (ES) and atmospheric pressure chemical ionization (APCI), the inlet systems themselves also provide the ions needed for mass spectrometry. In these cases, the method of introducing the sample becomes the method of ionization, and the two are not independent. This consideration can be important. For example, electrospray produces abundant... 

API interfaces have two available modes for operation, electrospray ionization (ESI) and atmospheric-pressure chemical ionization (APCI). The mechanistic aspects of ESI [10-12] and APCI [13] have been well covered in the literature. ESI, regarded as the softer, more versatile of the two methods, is able to ionize extremely polar/nonvolatile molecules, sometimes difficult for APCI. APCI mass spectra often contain fragment ions from the analyte due to the... 

Electrospray is surely the ionization method most widely employed for the liquid chromatography (LC)-MS coupling (Cappiello, 2007). The possibility of performing ionization at atmospheric pressure [also obtained in the case of atmospheric pressure chemical ionization (APCI) and atmospheric pressure photoionization (APPI), allows the direct analysis of analyte solutions. However, some problems arise from the intrinsically different operative conditions of the two analytical methods. First, there are the high-vacuum conditions that must be present at the mass analyzer level. Second, the mass spectrometers generally exhibit a low tolerance for the nonvolatile mobile-phase components, usually employed in LC conditions to achieve high chromatographic resolution. 

LC-MS using atmospheric pressure ionization (LC-API-MS) has dramatically changed the analytical methods used to detect polar pollutants in water. Most API mass spectrometers offer two interfaces electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI), both of which can be operated in positive and negative ion mode. ESI transfers ions from solution into the gas phase, whereas APCI ionizes in the gas phase. Analytes occurring as ions in solution may be best analyzed by ESI, while nonionic analytes may be well suited for APCI. What must always be taken into consideration is the relations between analyte properties and the chosen method of chromatographic separation. 

Atmospheric pressure ionization (API). The need to analyze polar componnds and the necessity to interface LC with MS led to the development of techniqnes where the ionization occurs at atmospheric pressure outside the vacuum chamber, and the resulting ions are transferred directly into the mass analyzer. Electrospray ionization (ESI) is the most successful of the API methods because of the range of molecular masses to which it can be applied, from small molecules to proteins. Other API methods include atmospheric pressure chemical ionization (APCI) and atmospheric pressure photo-ionization (APPI), and also the recently developed surface ionization methods such as desorption electrospray ionization (DESI) and direct analysis in real time (DART) (see below and Sections 2.2.2 and 2.2.3). 

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... 

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. 

The successful on-line interfacing of several ion sources has made them dominant players in quantitative analyses using mass spectrometry. These include electron ionization (El) and chemical ionization (Cl) both coupled to GC, and the atmospheric pressure ionization (API) methods of atmospheric pressure chemical ionization (APCI) atmospheric pressure photoionization (APPI), and electrospray ionization (ESI) coupled to LC. In addition, matrix assisted laser desorption ionization (MALDI) is seeing increased application in off-line LC/MS applications. 

Mass spectrometric detector selectivity provides imequivocal identification of target compoimds. By targeting the MW and by using specific software, fully automated peak recognition is possible. Compoimds need to be efficiently ionized for their detection. The single-quadmpole Waters ZQ is equipped with the two commonly available ionization sources electrospray ionization (ESI) and atmospheric pressure chemical ionization (APCI). As most of the compounds to be examined were basic, electrospray with positive ionization was our method of choice. The selection of E SI was supported by previous experience gained over the last three years in our laboratory about 96% of the identified compounds, corresponding to more than 9,000 different molecules, were successfully analyzed with the ESI interface. 

The advent of atmospheric-pressure ionization (API) provided a method of ionizing labile and nonvolatile substances so that they could be examined by mass spectrometry. API has become strongly linked to HPLC as a basis for ionizing the eluant on its way into the mass spectrometer, although it is also used as a stand-alone inlet for introduction of samples. API is important in thermospray, plasmaspray, and electrospray ionization (see Chapters 8 and 11). 

When mass spectrometry was first used as a routine analytical tool, El was the only commercial ion source. As needs have increased, more ionization methods have appeared. Many different types of ionization source have been described, and several of these have been produced commercially. The present situation is such that there is now only a limited range of ion sources. For vacuum ion sources, El is still widely used, frequently in conjunction with Cl. For atmospheric pressure ion sources, the most frequently used are ES, APCI, MALDI (lasers), and plasma torches. 

A liquid chromatography-mass spectrometry (LC-MS) method that can quantitatively analyze urinar y normal and modified nucleosides in less than 30 min with a good resolution and sufficient sensitivity has been developed. Nineteen kinds of normal and modified nucleosides were determined in urine samples from 10 healthy persons and 18 breast cancer patients. Compounds were separ ated on a reverse phase Kromasil C18 column (2.1 mm I.D.) by isocratic elution mode using 20 mg/1 ammonium acetate - acetonitrile (97 3 % v/v) at 200 p.l/min. A higher sensitivity was obtained in positive atmospheric pressure chemical ionization mode APCI(-i-). 

An on-line chromatography/atmospheric pressure chemical ionization tandem mass spectrometry (LC-APCI/MS/MS) methods was developed for rapid screen of pharmacokinetics of different drugs, including 5 (98RCM1216). The electron impact mass spectrum of 5 and ethyl 9,10-difluoro-3-methyl-7-oxo-2,3-dihydro-7Ff-pyrido[l,2,3- fe]-l,4-benzoxazine-6-carboxylate was reported (97MI28). Electron impact/Fourier transform... 

---