Thermospray interfaces

The emergence of thermospray ionization heralded a first ideal interface for a wide range of molecules [30,31]. With the introduction of this interface, LC/MS was accepted as a routine analytical technique. A major beneficiary of this interface was the pharmaceutical industry, which used this system to characterize drugs and metabolites. The construction and basic principle of thermospray ion source was discussed in Section 2.14 briefly, it consists of a heated probe, a desolvation chamber, and an ion extraction skimmer. When passed through a resistively heated capillary, the HPLC effluent, emerges as a mist of fine droplets into a heated desolvation chamber. Ionization of the solute molecules occurs by direct evaporation of the preformed ions or solvent-mediated chemical ionization. Thus, unlike the interfaces discussed above, the thermospray system acts as an ion source as well as an interface. Thermospray is ideally suited to coupling with conventional wide-bore columns. It is, however, confined primarily to reversed-phase HPLC separations, and it is less compatible with nonvolatile 

---

Thermospray interface. Provides liquid chromatographic effluent continuously through a heated capillary vaporizer tube to the mass spectrometer. Solvent molecules evaporate away from the partially vaporized liquid, and analyte ions are transmitted to the mass spectrometer s ion optics. The ionization technique must be specified, e.g., preexisting ions, salt buffer, filament, or electrical discharge. 

In summary, it can be said that prior to the development of the thermospray interface there were an increasing nnmber of reports of the analytical application of LC-MS [3] bnt in this present anthor s opinion, based on a nnmber of years of using a moving-belt interface, the technique could not be considered to be routine . The thermospray interface changed this and with the commercial intro-dnction of the combined APCI/electrospray systems in the 1990s the technique, for it now may be considered as a true hybrid technique, has reached maturity (although this should not be taken as a suggestion that there will be no further developments). 

The advantages and disadvantages of this type of interface, particnlarly in comparison to the moving-belt interface which was available at the same time, are listed below. This was one of the first LC-MS interfaces to be made commercially available and, although used in a number of laboratories, its development was halted premamrely by the introduction of the thermospray interface (as we shall see later). 

The thermospray interface overcame many of the problems enconntered with the moving-belt and direct-liquid-introdnction interfaces and with the advent of this, LC-MS became a routine analytical tool in a large number of laboratories. This was reflected in the fact that this was the first type of interface made available commercially by the majority of the mannfacturers of mass spectrometers. 

The introduction of the thermospray interface provided an easy-to-use LC-MS interface and was the first step in the acceptance of LC-MS as a routine analytical technique. It soon became the most widely used LC-MS interface of those available in the mid to late 1980s. 

A group of techniques employing differential selection of solute ions relies on nebulisation and ionisation of the eluent, with some discrimination of ion selection in favour of the solute. Main representatives are APCI [544] and thermospray [545]. In a thermospray interface a supersonic jet of vapour and small droplets is generated out of a heated vaporiser tube. Controlled, partial vaporisation of the HPLC solvent occurs before it enters the ion source. Ionisation of nonvolatile analytes takes place by means of solvent-mediated Cl reactions and ion evaporation processes. Most thermospray sources are fitted with a discharge electrode. When this is used, the technique is called plasmaspray (PSP) or discharge-assisted thermospray. In practice, many... 

With the thermospray interface (Figure 4.38(a)), the mobile phase, usually containing an ammonium ethanoate buffer, is passed through a heated probe (350-400°C) into an evacuated source chamber where it forms a supersonically expanding mist of electrically charged droplets. The liquid evaporates to leave charged solid particles which then release molecular ions such as MH+ and, VI by an ammonia chemical ionization (Cl) process. The analyte ions are skimmed off into the mass spectrometer whilst the vaporized solvent is pumped away. An electron beam is also employed to enhance the production of ions by Cl. 

The feasibility of online SPE LC/MS/MS has been tested since the introduction of thermospray ionization. In an early research paper by Lant and Oxford (1987), a prototype online SPE LC/MS system was set up and successfully applied for the measurement of labetalol, a hypertension drug and a- and /J-adrenergic receptor, in plasma. This system was set up by coupling an advanced automated sample processor (AASP, Varian, Walton-on-Thames, UK) with a reversed-phase column, a ten-port switching valve, and an MS equipped with thermospray interface (Vestec, Houston, Texas) (Blakley et al. 1980, Blakley and Vestal 1983). 

C. R. Blakley and M. L. Vestal. Thermospray Interface for Liquid Chromatography/Mass Spectrometry. Anal Chem., 55(1983) 750-754. 

Ion Rathe, a technician in the LC-MS laboratory at MDS Pharma Services, checks out the thermospray interface on one of the LC-MS units in this laboratory. 

Fig. 11.2. Schematic of a thermospray interface. A cartridge heater B copper block brazed to stainless steel capillary C capillary D copper tube E ion lenses E quadrupole mass analyzer G line to rotary vane pump H ion exit aperture J source heater. Reproduced from Ref. [30] by permission. American Chemical Society, 1983.

Blakley, C.R. Vestal, M.L. Thermospray Interface for Liquid Chromatogra-phy/Mass Spectrometry. Anal. Chem. 1983, 55, 750-754. 

The two most common LG/MS interfaces used for routine quantitative analyses are APCI and APT electrospray. The principles of these techniques in direct infusion analyses have been described earlier (see Sections 3.3 and 3.4). As APTelectrospray has a broader application profile, its use is more widespread than APCI. Other configurations including El, atmospheric pressure photoionization (APPl), and thermospray interfaces with liquid chromatographs are available but are less commonly used for high throughput or routine analysis. 

Most of the direct and indirect (transport) interfaces described here use chemical ionization (c.i.) ion-sources, which are not well suited to such polar, non-volatile compounds as tri- and higher oligosaccharides. The thermospray interface, which can operate on an ion-evaporative mode, is capable of producing intact molecular ions from such nonvolatile, polar molecules and should be useful in oligosaccharide analysis. Molecules of this type, however, can also be easily analyzed by fast-atom-bombardment ionization, and use of this technique, coupled to direct liquid introduction and moving-belt interfaces, has been reported. The latter system has been applied to complex oligosaccharide analysis. ... 

LC-PB-MS has been investigated as a potential confirmatory method for the determination of malachite green in incurred catfish tissue (81) and of cephapirin, furosemide, and methylene blue in milk, kidney, and muscle tissue, respectively (82). Results showed that the mobile-phase composition, nebulization-de-solvation, and source temperature all play an important role in the sensitivity of the method. The sensitivity increases with decreasing heat capacity of the mobile phase in the order methanol acetonitrile isopropanol water and with decreasing flow rate. A comparison of the PB with the thermospray interface showed that less structural information was provided by the latter, whereas the sensitivity was generally lower with the thermospray interface. 

---