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

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 not mal, 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 (C) 2009 Elsevier B V. All rights reserved