Mass spectrometry in the search for uremic toxins

This article reviews the literature on the mass spectrometry (MS) that has been used in the research of uremic toxins. Gas chromatography/mass spectrometry (GC/MS) has been most often used for the analysis of low-molecular-weight compounds in uremic blood such as organic acids, phenols, and polyols. However, it cannot be used for the analysis of middle- to high-molecular-weight substances or for involatile compounds. The development of fast atom bombardment (FAB) and liquid secondary ion mass spectrometry (LSIMS) has made possible the analysis of middle-molecules and involatile low-molecular-weight substances such as peptides and nucleosides. The development of atmospheric pressure chemical ionization (APCI) has also lead to the analysis of involatile low-molecular-weight substances. The recent advances in ionization methods, such as electrospray ionization (ESI) and matrix-assisted laser desorption ionization (MALDI), have permitted the MS analysis of high-molecular-weight substances such as beta 2-microglobulin, a major component of dialysis amyloid. Liquid chromatography/mass spectrometry (LC/MS), using ESI, APCI, or FAB as an ionization method, is currently the preferred method for the analysis of low- to high-molecular-weight substances in uremic blood. ESI-LC/MS and matrix-assisted laser desorption ionization-time of flight mass spectrometry (MALDI-TOFMS) are useful for elucidating the structure of post-translationally modified proteins obtained from the blood and tissues of uremic patients. Post-translational modification such as the formation of advanced glycation end-products and carbamoylation is enhanced in uremic patients, and is considered to be responsible for some uremic symptoms. Laser microprobe MS is unique in its capability for the two-dimensional detection of atoms such as aluminum in a tissue section obtained from uremic patients. This review focuses on the mainstream research for discovering uremic toxins, specific uremic toxins identified or quantified using MS, and the MS analysis of post-translationally modified proteins in uremia. These studies have provided ample evidence that MS has played an important role in the search for uremic toxins.