Ionization of nonvolatiles

Three major difficulties have been generally met in directly combining LC with MS. The first concerns the ionization of nonvolatile and/or thermolabile analytes. The second is related to the mobile-phase incompatibility as result of the frequent use of nonvolatile mobile-phase buffers and additives in LC. The third is due to the apparent flow rate incompatibility as expressed in the need to introduce a mobile phase eluting from the column at a flow rate of 1 ml/min into the high vacuum of the MS. 

SIMS. Secondary Ion Mass Spectrometry is particularly suited for ionization of nonvolatile, polar, and thermally labile molecules. Liquid SIMS, using liquid glycerol matrices, is best done in the differentially-pumped external ion source, because matrix effects and the high vapor pressure of glycerol make liquid SIMS unsuitable for single cell low-pressure FTMS. 

M Dedieu, C. Juin, P.J. Arpino, G. Guiochon, Soft negative ionization of nonvolatile molecules by DLI of liquid solutions into a CI-MS, Anal. Chem., 54 (1982)2372. 

When LC is coupled with MS, three major problems generally arise. The first concerns the ionization of nonvolatile and/or thermolabile analytes. As MS operation is based on magnetic and electric fields that exert... 

Ionization of nonvolatile or thermally labile solutes is difficult. The ionization and thus the response in LC-MS analysis is limited by the ability to protonate or deprotonate the analytes of interest. However, difficulties have been overcome to make LC-MS a robust and routinely applicable tool in environmental laboratories. 

Ion spray ionization (ISI), an atmospheric pressure ionization (API) method for MS, was shown to be highly sensitive for polar compounds such as marine biotoxins. This is a soft ionization technique that eludes the difficulties of ionization of nonvolatile and/or thermally labile analytes and gives abundant molecular-related ions with negligible fragmentation. 

Another method for ionization of nonvolatile molecules is MALDl (matrix-assisted laser desorption ionization. Section 9.18A). Energy from laser bombardment of a sample adsorbed in a solid chemical matrix leads to generation of gas-phase ions that are detected by the mass spectrometer. Both MALDl and ESI are common ionization techniques for the analysis of biopolymers. 

Central to any measurements in mass spectrometry is the ionization of the sample molecules, and transfer of those ions into the vacuum required for operation of the mass spectrometer. The choice of ionization methods available to analytical and organic mass spectrometrists has expanded greatly in the past ten years, and now includes means for the ionization of nonvolatile as well as volatile molecules. Any of several methods might be chosen to address a particular problem, and each might provide satisfactory results. Since there is no single ionization method used exclusively with TLC/MS, this section of the chapter contains an overview of the most common methods of sample molecule ionization in mass spectrometry. 

The latest developments in mass spectrometry with respect to soft ionization of nonvolatile and thermolabile compounds have brought this technique to the level where it may open, and indeed has opened, new ways in cobalamin research, especially when integrated with HPLC. 

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