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 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.
Kikuchi
Kaori
K
Biomedical Research Laboratories, Kureha Corporation, Tokyo, Japan.
Itoh
Yoshiharu
Y
Tateoka
Ryoko
R
Ezawa
Atsuko
A
Murakami
Kenjiro
K
Niwa
Toshimitsu
T
D000818:Animals; D002853:Chromatography, Liquid / Q000379:methods*; D003408:Cresols / Q000097:blood; D004195:Disease Models, Animal; D006626:Hippurates / Q000097:blood; D006801:Humans; D007200:Indican / Q000097:blood; D007668:Kidney / Q000737:chemistry; D007676:Kidney Failure, Chronic / Q000097:blood* / Q000652:urine; D008297:Male; D055432:Metabolomics / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013463:Sulfuric Acid Esters / Q000097:blood; D014118:Toxins, Biological / Q000097:blood* / Q000652:urine
D003408:Cresols; D006626:Hippurates; D013463:Sulfuric Acid Esters; D014118:Toxins, Biological; C408690:4-cresol sulfate; D007200:Indican; C030514:hippuric acid