A novel UPLC-MS-MS method for simultaneous determination of seven uremic retention toxins with cardiovascular relevance in chronic kidney disease patients

Anal Bioanal Chem. 2013 Feb;405(6):1937-47. doi: 10.1007/s00216-012-6636-9. Epub 2013 Jan 11.

Abstract

Chronic kidney disease (CKD) is a devastating illness characterized by accumulation of uremic retention solutes in the body. The objective of this study was to develop and validate a simple, rapid, and robust UPLC-MS-MS method for simultaneous determination, in serum, of seven organic acid uremic retention toxins, namely uric acid (UA), hippuric acid (HA), indoxylsulfate (IS), p-cresylglucuronide (pCG), p-cresylsulfate (pCS), indole-3-acetic acid (IAA), and 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid (CMPF). Isotopically labeled internal standards (d(5)-HA; 1,3-(15)N(2)-UA, and d(5)-IAA) were used to correct for variations in sample preparation and system performance. Separation on a C18 column was followed by negative electrospray ionization and tandem mass spectrometric detection. Accuracy was below the 15 % threshold. Within-day precision varied from 0.60 to 4.54 % and between-day precision was below 13.33 % for all compounds. The applicability of the method was evaluated by analyzing 78 serum samples originating both from healthy controls and from patients at different stages of CKD. These results were compared with those obtained by use of conventional HPLC-PDA-FLD methods. A good correlation was obtained between both methods for all compounds.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Cardiovascular Diseases / blood
  • Cardiovascular Diseases / etiology
  • Case-Control Studies
  • Chromatography, High Pressure Liquid / methods*
  • Cresols / blood
  • Female
  • Furans / blood
  • Glucuronides / blood
  • Hippurates / blood
  • Humans
  • Indican / blood
  • Indoleacetic Acids / blood
  • Male
  • Propionates / blood
  • Renal Insufficiency, Chronic / blood*
  • Renal Insufficiency, Chronic / complications
  • Severity of Illness Index
  • Sulfuric Acid Esters / blood
  • Tandem Mass Spectrometry / methods*
  • Uremia / blood*
  • Uremia / complications
  • Uric Acid / blood

Substances

  • 4-cresylglucuronide
  • Cresols
  • Furans
  • Glucuronides
  • Hippurates
  • Indoleacetic Acids
  • Propionates
  • Sulfuric Acid Esters
  • Uric Acid
  • 4-cresol sulfate
  • indoleacetic acid
  • 3-carboxy-4-methyl-5-propyl-2-furanpropionic acid
  • Indican
  • hippuric acid