Metabolomic analysis of uremic toxins by liquid chromatography/electrospray ionization-tandem mass spectrometry

J Chromatogr B Analyt Technol Biomed Life Sci. 2010 Jun 15;878(20):1662-8. doi: 10.1016/j.jchromb.2009.11.040. Epub 2009 Dec 3.


We applied the metabolomic analysis of comprehensive small-molecular metabolites using liquid chromatography/electrospray ionization-tandem mass spectrometry (LC/ESI-MS/MS) and principal component analysis to identify uremic toxins accumulated in the serum of chronic renal failure (CRF) rats. CRF rats were produced by 5/6-nephrectomy. Indoxyl sulfate was demonstrated to be the first principal serum metabolite which differentiates CRF from normal, followed by phenyl sulfate, hippuric acid and p-cresyl sulfate. Then, we measured the serum levels of indoxyl sulfate, phenyl sulfate, hippuric acid and p-cresyl sulfate by the selected reaction monitoring (SRM) of LC/ESI-MS/MS, and demonstrated that these serum levels were markedly increased in CRF rats as compared with normal rats. As creatinine clearance decreased, the serum levels of the metabolites increased.

MeSH terms

  • Animals
  • Chromatography, Liquid / methods*
  • Cresols / blood
  • Disease Models, Animal
  • Hippurates / blood
  • Humans
  • Indican / blood
  • Kidney / chemistry
  • Kidney Failure, Chronic / blood*
  • Kidney Failure, Chronic / urine
  • Male
  • Metabolomics / methods*
  • Rats
  • Rats, Sprague-Dawley
  • Spectrometry, Mass, Electrospray Ionization / methods*
  • Sulfuric Acid Esters / blood
  • Toxins, Biological / blood*
  • Toxins, Biological / urine


  • Cresols
  • Hippurates
  • Sulfuric Acid Esters
  • Toxins, Biological
  • 4-cresol sulfate
  • Indican
  • hippuric acid