Interface atmospheric-pressure chemical ionisation

Right from the outset of the 1990s, a selection of those interfaces that could be adapted to a routine LC-MS analysis was observable. This trend had been initiated by pharmacological and pharmaceutical research, although it had the TSP interface at its disposal, which was a well-adapted and reliable type of interface that had shown its fiiU capacity in manifold appliances. The sample material, being available only in very limited quantities for such research, and improved separation techniques, as, for example, capillary electrophoresis (CE) or capillary zone electrophoresis (CZE) necessitated different types of interfaces that could be operated with considerably smaller amounts of sample than the TSP interface, which reached its optimized sensitivity with flow rates of about 2 mL min. Such a desirably lower sample demand is guaranteed by atmospheric pressure ionisation (API) interfaces, atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI) interface. 

Ionisation methods investigated earlier, including thermospray, fast atom bombardment, and particle beam interfaces have been replaced by electrospray imiiza-tion (ESI) interfaces. Atmospheric pressure chemical ionisation (APCI) has also been applied but is less sensitive towards the PANOs. A combination of ESI with reversed-phase HPLC using acid mobile phases to protonate the PA molecules has most often been used [41]. 

LC-APCI-MS is a derivative of discharge-assisted thermospray, where the eluent is ionised at atmospheric pressure. In an atmospheric pressure chemical ionisation (APCI) interface, the column effluent is nebulised, e.g. by pneumatic or thermospray nebulisation, into a heated tube, which vaporises nearly all of the solvent. The solvent vapour acts as a reagent gas and enters the APCI source, where ions are generated with the help of electrons from a corona discharge source. The analytes are ionised by common gas-phase ion-molecule reactions, such as proton transfer. This is the second-most common LC-MS interface in use today (despite its recent introduction) and most manufacturers offer a combined ESI/APCI source. LC-APCI-MS interfaces are easy to operate, robust and do not require extensive optimisation of experimental parameters. They can be used with a wide variety of solvent compositions, including pure aqueous solvents, and with liquid flow-rates up to 2mLmin-1. 

In off-line coupling of LC and MS for the analysis of surfactants in water samples, the suitability of desorption techniques such as Fast Atom Bombardment (FAB) and Desorption Chemical Ionisation was well established early on. In rapid succession, new interfaces like Atmospheric Pressure Chemical Ionisation (APCI) and Electrospray Ionisation (ESI) were applied successfully to solve a large number of analytical problems with these substance classes. In order to perform structure analysis on the metabolites and to improve sensitivity for the detection of the various surfactants and their metabolites in the environment, the use of various MS-MS techniques has also proven very useful, if not necessary, and in some cases even high-resolution MS is required. 

These problems have largely been solved by the development of a wide variety of powerful LC-MS interfaces (reviewed in Refs. [1-3]). In the following paragraphs, the two most widely used atmospheric pressure ionisation (API) systems, namely atmospheric pressure chemical ionisation (APCI) and electrospray ionisation (ESI), are briefly described, along with the older technique of thermospray ionisation... 

For sensitive quantification in LC-MS analysis of non-ionic surfactants, selection of suitable masses for ion monitoring is important. The nonionic surfactants easily form adducts with alkaline and other impurities present in, e.g. solvents. This may result in highly complicated mass spectra, such as shown in Fig. 4.3.1(A) (obtained with an atmospheric pressure chemical ionisation (APCI) interface) and Fig. 4.3.2 (obtained with an ESI interface). 

Methyl, nitro and chlorophenols (EPA priority pollutants) LC-MS (atmospheric pressure chemical ionisation and ion spray interfaces) ppt [18]... 

Polar pesticides - LC-MS atmospheric pressure chemical ionisation interface sub ppb [31]... 

Sjoberg, J.R. Markides, K.E. Capillary Column Supercritical Fluid Chromatography-Atmospheric Pressure Ionisation Mass Spectrometry Interface Performance of Atmospheric Pressure Chemical Ionisation and Electrospray Ionisation,", 7. Chromatogr. A 855, 317-327 (1999). 

Sjoberg, P.J. and Markides, K.E., Capillary column supercritical fluid chromatography-atmospheric pressure ionisation mass spectrometry interface performance of atmospheric pressure chemical ionisation and electrospray ionisation, J. Chromatogr. A, 855(1), 317, 1999. 

Atmospheric pressure chemical ionisation (APCI) is a technique that also creates gas phase ions from the liquid sample. It too takes place at atmospheric pressure and uses a similar interface to that in ESI. As in ESI, the sample solution is mixed with a nebulising gas and the sample arrives in the spray chamber as a fine mist of droplets or spray. In APCI, an extra component - a corona discharge - is used to further ionise the analyte droplets in a manner similar to straightforward Cl (Figure 2.34). While a small amount of fragmentation may occur, the technique is still considered to be a soft ionisation one. The gas-phase ionisation in APCI is more effective than ESI for analysing less polar species. ESI and APCI are complementary methods. 

On-line mass spectrometry has been implemented in pharmaceutical processes for monitoring raw materials andproducts ". In this particular application, dilution of the samples is carried out by a membrane interface coupled directly to the atmospheric pressure chemical ionisation source of a quadrupole mass spectrometer for real-time analysis. Continuous online MS has also been used for monitoring fermentation processes in the brewing industry. ... 

Clinton, R. and Creaser, C.S. (2005) Real-time monitoring of a pharmaceutical process reaction using a membrane interface combined with atmospheric pressure chemical ionisation mass spectrometry. Anal Chim Acta, 539 (1-2), 133-140. 

The most recent significant advance in plant hormone analysis has been the use of combined HPLC-MS for the analysis of GA conjugates, lAA conjugates and cytokinins. A number of interfaces have been developed for HPLC-MS, including thermospray, atmospheric pressure chemical ionisation, electrospray, particle beam, continuous flow fast atom bombardment (FAB) and frit-FAB (see reference [94]). GA standards have been analysed by HPLC-MS with a thermospray interface [95], an atmospheric pressure chemical ionisation interface has been used with GA conjugates [96] and cytokinins [97] while ion spray and plasma spray have been used to analyse ABA and its metabolites [98]. There are, however, many more reports on the use of frit-FAB HPLC-MS for the analysis of not only standards, but also endogenous hormones and their isotopically-labelled metabolites [18-23,99-101]. 

Probably the most common separation systems used in the laboratory today require the sample to be in solution (e.g. HPLC, CE). The solvent may be aqueous or solvent based. However, onemL of such solution yields far too much vapour (1-2L) to be accommodated by a mass spectrometer s vacuum system. Thus the aim of a sample introduction system for such solutions would require the sample to be ionised and the solvent to be separated from these sanple ions. In addition the interface must maintain the integrity of the chromatography. The chromatographic separation must be maintained as well as allowing sufficient analyte through to generate a mass spectmm. A number of methods have been developed to do this, but the two main techniques used today are electrospray and atmospheric pressure chemical ionisation (APCI for short). These are described below under ionisation techniques. 

Atmospheric-pressure chemical ionisation was favoured by Horning et al. [3], whereas (2) Scott et al. [4] applied a moving-wire system which became transformed and finally resulted in the moving-belt interface. (3) The research of Arpino and his co-workers [5] led further in the direction initiated by Talroze [2], which after all had brought about the direct liquid introduction interface. 

Figure 4.2 Membrane inlet msiss spectrometry (a) schematic diagram of the membrane interface for APCI/MS and (b) schematic diagram of the donor/acceptor flow across the microporous membrane [69], Reprinted from Analytica Chimica Acta, 539, Clinton, R., Creaser, C.S., Bryant, D., Real-time Monitoring of a Pharmaceutical Process Reaction Using a Membrane Interface Combined with Atmospheric Pressure Chemical Ionisation Mass Spectrometry, 133-140. Copyright (2005), with permission from Elsevier...

Clinton, R., Creaser, C.S., Bryant, D. (2005) Real-time Monitoring of a Pharmaceutical Process Reaction Using a Membrane Interface Combined with Atmospheric Pressure Chemical Ionisation Mass Spectrometry. Anal. Chim. Acta 539 133-140. 

The introduction of liquid samples into the mass spectrometer has proved especially difficult. However, the advent of electrospray ionisation (ESI) and atmospheric pressure chemical ionisation (APCI) have overcome this problem and revolutionized the interfacing of HPLC with mass spectrometry. This success has pointed the way toward a major change in the mass spectrometric analysis of vitamin D, its analogs, and their metabolites. A disadvantage at the present time is that ionization using ESI and APCI is less efficient than the EI(+) used in GC-MS, but the immediate advantage is that it obviates the need for derivatiza-tion. 

In thermospray interfaces, the column effluent is rapidly heated in a narrow bore capillary to allow partial evaporation of the solvent. Ionisation occurs by ion-evaporation or solvent-mediated chemical ionisation initiated by electrons from a heated filament or discharge electrode. In the particle beam interface the column effluent is pneumatically nebulised in an atmospheric pressure desolvation chamber this is connected to a momentum separator where the analyte is transferred to the MS ion source and solvent molecules are pumped away. Magi and Ianni (1998) used LC-MS with a particle beam interface for the determination of tributyl tin in the marine environment. Florencio et al. (1997) compared a wide range of mass spectrometry techniques including ICP-MS for the identification of arsenic species in estuarine waters. Applications of HPLC-MS for speciation studies are given in Table 4.3. 

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