Thermospray ionization source

After overcoming the instability of the thermospray ionization source, a sensitivity of 2 ng/mL was achieved with a calibration range of 10 to 103 ng/mL for human plasma samples. In recent years, the online SPE LC/MS/MS technology has matured and is now easy to build and use. It is used widely in the pharmaceutical industry (Jemal et al. 2000 Hsieh 2004 Hennion 1999). 

Figure 2.14. Block diagram of thermospray ionization source. (Reproduced from C. Dass, Principles and Practice of Biological Mass Spectrometry, WUey-Interscience, 2001.)...

Thermospray is both a liquid inlet system for a mass spectrometer and, at the same time, an ionization source. 

Figure 9.4 Soaematic diagram of a thexmospray interface ionization source connected to a quadrupole mass analyzer and Insert indicating the mechanism of vapor production by the heated thermospray.

A number of interfaces such as thermospray (TSP), ionspray (IS), atmospheric chemical ionization (APCI) and electrospray (ES) can tolerate much higher flow rates without requiring that the flow be split at the end of the LC column. Ions that are produced in atmospheric pressure ionization sources are moved directly into the mass spectrometer through small apertures. 

The instrumentation and interfaces that had been used up to 1998 in CWC-related LC/MS analysis were summarized previously (4). At that time, sources that operate at atmospheric pressure, using electrospray ionization (ESI) or atmospheric pressure chemical ionization (APCI), were displacing their predecessors that used thermospray ionization or continuous flow fast atom bombardment. Atmospheric pressure ionization (API), either ESI or APCI, is now the method of choice in CWC-related analysis and will be the focus of this current review. A small number of recent applications involving alternative types of ionization are also included. For earlier applications of LC/MS to chemical weapons (CW) analysis, using thermospray and other ionization methods, the reader is referred to our previous review (4). The other major trend has been the increasing availability and ease of use of less-expensive bench-top quadrupole and... 

Attempts to develop a GC/MS method for this metabolite were unsuccessful, no doubt because of thermal instability. An LC/MS/MS method using thermospray ionization, after derivatization to the dimethyl ester, gave a modest detection limit of 25 ng/ml, again probably due to poor thermal stability, in this case, in the thermospray ion source (12). A substantial improvement has recently been achieved (detection limit 1 ng/ml) using LC/ESI/MS/MS without derivatization (31). Concentration from acidified urine was achieved on... 

Blakely and Vestal [24] employed the thermospray system with the quadrupole mass spectrometer and demonstrated that it could provide stable vaporization and ionization at flow rates up to 2 ml/min with an aqueous mobile phase. If the mobile phase contained a significant amount of ions in solution ca. 10 to 1.0 M) no extra thermal ionization source is required to achieve detection of many non-volatile solutes at the sub-microgram level. They found that with weakly ionized mobile phases, a conventional electron beam needs to be used to provide gas-phase reagent ions for the chemical ionization of the solute. The thermospray system has been effectively used by Voyksner et al. [25] in the analysis of cancer drugs. 

Product-ion MS-MS spectra of carbamates were investigated by Chiu et al. [24], using thermospray ionization and either protonated or ammoniated molecules as precursor ions. The fragmentation is similar to that in in-source CID. For A -methyl carbamates, the loss of 57 due to methyl isocyanate is a characteristic feature. In N-oxime carbamates, the fragmentation is directed from the oxime rather than from the carbamate group. 

Produce ions from neutral molecules in the vapor phase. This takes place in the ion source. As can be seen in Fig. 1, there are several modes of ion sources. Of those, the most used in LC-MS are electron spray ionization (ESI), chemical ionization (Cl), thermospray ionization (TSP), fast-atom bombardment (FAB), and electron impact (El). 

A typical thermospray ionization mass spectrum for a sulfonylurea contains a weak protonated molecular ion and three to four characteristic fragment ions. Figure 2 shows the thermospray positive ion mass spectrum for HARMONY. The spectrum contains a protonated molecular ion at m/z 388, the sulfonamide ammonium adduct ion at m/z 239 and the protonated triazine urea fragment ion at m/z 184. At the same time, Figure 3 shows the positive ion thermospray mass spectrum for LONDAX. It contains the protonated pyrimidine amine at m/z 156, the protonated pyrimidine urea is at m/z 199 and the sulfonamide ammonium adduct ion at m/z 247. LONDAX (bensulfuron methyl) is a sulfonylurea rice herbicide and it elutes between EXPRESS and CLASSIC if we use the LC conditions outlined in Figure 1. HARMONY and LONDAX thermospray spectra were generated with the thermospray vaporizer tip temperature at 150°C and the source block temperature at 320°C. 

Significant advances with the ionization source have been made. The pioneering work of many outstanding scientists with moving belt [34-36], direct liquid introduction (DLI) [37-39], thermospray ionization (TSI) [40,41], and ESI [42-44] set the stage for the development of modem ionization sources for high-performance LC-MS analysis. 

The commonly used interfaces are the electrospray ionization (ESI) source, thermospray ionization (TSI), atmospheric pressure chemical ionization (APCI), and particle beam ionization. The choice depends largely on the polarity and thermal stability of the analyte. Electrospray ionization is preferred for polar and ionic and veiy large molecules such as proteins and peptides. Atmospheric pressure... 

Thermospray was in several ways the forerunner of electrospray and atmospheric pressure chemical ionization sources, and in current practice has largely been superseded by them. Thermospray (TSP) is a combination of interface and ion source for LC-MS and other liquid-phase sample introduction systems [7,31-33]. A continuous flow of liquid is rapidly vaporized in a resistively heated metal capillary tube forming a supersonic... 

Thermospray and, more recently, electrospray ionization have found wide application as an interface technology between HPLC instruments and mass spectrometers. They represent powerful techniques for the analysis of complex lipids directly from solutions (Henion and Lee, 1990 Murphy, 1993). In most instances, the total HPLC eluant can be sent directly into the heated thermospray ion source. Here, the combination of heat and eluant velocity creates a plume of small-diameter particles suspended in a vapor (nebulization). A strong electric charge forms on the surface of the liquid particles and as the droplets evaporate the increase in charge ionizes analyte molecules that are discharged directly from the droplet into the gas phase. From here, they may enter the mass spectrometer directly. 

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... 

The basic function of the mass spectrometer is to measure the mass-to-charge ratios of analyte ions, and the various designs of mass spectrometers have been described in detail in the literature. The HPLC-MS system has four main components consisting of a sample inlet, an ion source, a mass analyzer, and finally an ion detector. The sample introduction system vaporizes the HPLC column effluent. The ion source produces ions from the neutral analyte molecules in the vapor phase. Several designs of ion sources have been used over the past years including electrospray ionization (ESI), atmospheric pressure chemical ionization (APCI), thermospray ionization (TSP), continuous flow fast atom bombardment (FAB), and atmospheric pressure photoionization (APPI). The inductively coupled plasma (ICP) is a hard ionization source and is used specifically for the detection of metals and metals in adducts or in organometallic compounds. Generally, ICP-MS is used for elemental speciation analysis with HPLC, which has been described elsewhere in... 

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