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

J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Nov 1;878(29):2997-3002. doi: 10.1016/j.jchromb.2010.09.006. Epub 2010 Sep 15.


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.

Publication types

  • Evaluation Study

MeSH terms

  • Adsorption
  • Animals
  • Carbon / administration & dosage*
  • Carbon / chemistry
  • Chromatography, Liquid / methods*
  • Hippurates / blood
  • Hippurates / metabolism
  • Hippurates / urine
  • Indican / blood
  • Indican / metabolism
  • Indican / urine
  • Kidney Failure, Chronic / blood
  • Kidney Failure, Chronic / metabolism
  • Kidney Failure, Chronic / therapy*
  • Kidney Failure, Chronic / urine
  • Male
  • Metabolomics
  • Oxides / administration & dosage*
  • Oxides / chemistry
  • Rats
  • Rats, Sprague-Dawley
  • Tandem Mass Spectrometry / methods*
  • Toxins, Biological / blood*
  • Toxins, Biological / metabolism
  • Toxins, Biological / urine*
  • Uremia / blood
  • Uremia / metabolism
  • Uremia / therapy*
  • Uremia / urine


  • Hippurates
  • Oxides
  • Toxins, Biological
  • Carbon
  • AST 120
  • Indican
  • hippuric acid