Mass spectrometry incompatibility

The characteristics of an ideal liquid chromatography-mass spectrometry interface have been discussed, with emphasis having been placed upon the major incompatibilities of the two component techniques that need to be overcome to allow the combination to function effectively. 

Before considering these in detail, it is necessary to revisit the inherent incompatibilities between mass spectrometry and liqnid chromatography. These are, as discussed previously, that HPLC utilizes a liquid mobile phase, often containing significant amounts of water, flowing typically at 1 mlmin while the mass spectrometer must be maintained under conditions of high vacuum, i.e. around 10- torr (1.333 22 x IQ- Pa). 

The need for a more definitive identification of HPLC eluates than that provided by retention times alone has been discussed previously, as have the incompatibilities between the operating characteristics of liquid chromatography and mass spectrometry. The combination of the two techniques was originally achieved by the physical isolation of fractions as they eluted from an HPLC column, followed by the removal of the mobile phase, usually by evaporation, and transfer of the analyte(s) into the mass spectrometer by using an appropriate probe. 

Peak purity tests are used to demonstrate that an observed chromatographic peak is attributable to a single component. Mass spectrometry is the most sensitive and accurate technique to use for peak purity evaluation because of the specific information derived from the analysis. However, a good number of HPLC methods use mobile phase conditions that are incompatible with mass spectrometry detection. In this case, PDA spectrophotometers using peak purity algorithms may be used to support the specificity of the method. Almost all commercially available diode array detectors are equipped with proprietary software that will perform these calculations. Although this technique is more universal in application to HPLC methods, the data provided is neither particularly... 

Somsen, G. W, Mol, R., and de Jong, G. J. (2006). Micellar electrokinetic chromatography-mass spectrometry combining the supposedly incompatible. Anal. Bioanal. Chem. 384, 31—33. 

Interfacing of solution-based separation techniques with mass spectrometry has historically been a challenge because of the incompatibility of the used solvent with the vacuum system. Standard electron impact (El) ionization with techniques such as particle beam require samples to be vaporized under high vacuum for ion formation to occur. 

Samples sufficiently volatile for gas chromatography are readily handled by mass spectrometry. The two instruments are chiefly incompatible in the vast difference in operating pressures 760mmHg at the column exit and 10 -10" mm Hg in the analyser of the mass spectrometer. There are two solutions the vacuum system can be designed to accommodate a substantial fraction of the column effluent or a molecular separator can be employed to enrich sample relative to carrier gas effecting pressure reduction prior to transmission to the ion source. 

When compared to other mass-sensitive detectors such as flame ionization (FID), refractive index (RI), and mass spectrometry (MS), the ELSD can detect analytes without interference from organic modifiers and additives. The use of organic solvents in FID limits usefulness due to an increase in baseline noise, and FID cannot be used with HPLC. RI detectors, in general, are less sensitive than other detectors and are incompatible with gradient elution. Although the MS can be used with modifier gradients, ionization efficiencies... 

In the past the efficient on-line characterization of flavor progenitors by mass spectrometry has been limited by the polar and labile character of these compounds. Combining HPLC with mass spectrometry could have been the method of choice for the analysis of glycoconjugates. But in order to transform molecules from solution to ions in the gas-phase one had to deal with three major incompatibilities (/) ... 

Mass spectrometry has been applied in electrochemical investigations predominantly as an ex situ method because of the obvious incompatibility of the high vacuum needed for all types of mass spectrometry and the presence of a liquid electrolyte solution. Because of the amount of information provided in a mass spectrum, there have been various attempts to couple mass spectrometers with electrochemical cells as described below. 

The online coupling of a separation device with mass spectrometry is an analytical approach that can help in the analysis of real-world samples such as environmental samples and biological tissues and fluids. This online marriage between two stand-alone analytical techniques can provide an unequivocal characterization of individual components of such complex samples and greatly increases the information content of those components. Several issues that must be addressed to achieve an ideal combination. A major concern is the pressure mismatch. The solvent incompatibility also becomes an issue in the coupling of LC and CE with mass spectrometry. Thus, online coupling requires an interface that can transport the separated components into the ion source without affecting their resolution or the performance of a mass spectrometer. Not all types of mass spectrometers... 

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