Metabolomic search for uremic toxins as indicators of the effect of an oral sorbent AST-120 by liquid chromatography/tandem mass spectrometry

An oral sorbent AST-120 composed of spherical porous carbon particles has superior adsorption ability for certain small-molecular-weight organic compounds known to accumulate in patients with chronic renal failure (CRF) A metabolomic approach was applied to search for uremic toxins as possible indicators of the effect of AST-120 Serum metabolites in normal and CRF rats before and after administration of AST-120 for 3 days were analyzed by liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) and principal component analysis Further serum and urine levels of the indicators were quantified by selected reaction monitoring of LC/ESI-MS/MS Indoxyl sulfate was the first principal serum metabolite which could differentiate CRF from both normal and AST-120-administered CRF rats followed by hippuric acid phenyl sulfate and 4-ethylphenyl sulfate CRF rats showed increased serum levels of indoxyl sulfate hippuric acid phenyl sulfate 4-ethylphenyl sulfate and p-cresyl sulfate Administration of AST-120 for 3 days to the CRF rats reduced the serum and urine levels of these metabolites In conclusion indoxyl sulfate is the best indicator of the effect of AST-120 in CRF rats Hippuric acid phenyl sulfate and 4-ethylphenyl sulfate are suggested as the additional indicators 4 Ethylphenyl sulfate is a newly identified uremic substance (C) 2010 Elsevier B V All rights reserved