title: A novel UPLC-MS-MS method for simultaneous determination of seven uremic retention toxins with cardiovascular relevance in chronic kidney disease patients.
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.
authors.affiliation: Separation Science Group, Department of Organic Chemistry, Ghent University, Krijgslaan 281-S4bis, 9000 Ghent, Belgium.
authors.forename: Jente
authors.initials: J
authors.lastname: Boelaert
authors.forename: Frédéric
authors.initials: F
authors.lastname: Lynen
authors.forename: Griet
authors.initials: G
authors.lastname: Glorieux
authors.forename: Sunny
authors.initials: S
authors.lastname: Eloot
authors.forename: Maria
authors.initials: M
authors.lastname: Van Landschoot
authors.forename: Marie-Anne
authors.initials: MA
authors.lastname: Waterloos
authors.forename: Pat
authors.initials: P
authors.lastname: Sandra
authors.forename: Raymond
authors.initials: R
authors.lastname: Vanholder
mesh_terms: D002318:Cardiovascular Diseases / Q000097:blood / Q000209:etiology; D016022:Case-Control Studies; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D003408:Cresols / Q000097:blood; D005260:Female; D005663:Furans / Q000097:blood; D020719:Glucuronides / Q000097:blood; D006626:Hippurates / Q000097:blood; D006801:Humans; D007200:Indican / Q000097:blood; D007210:Indoleacetic Acids / Q000097:blood; D008297:Male; D011422:Propionates / Q000097:blood; D051436:Renal Insufficiency, Chronic / Q000097:blood* / Q000150:complications; D012720:Severity of Illness Index; D013463:Sulfuric Acid Esters / Q000097:blood; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014511:Uremia / Q000097:blood* / Q000150:complications; D014527:Uric Acid / Q000097:blood
chemical_list: C485699:4-cresylglucuronide; D003408:Cresols; D005663:Furans; D020719:Glucuronides; D006626:Hippurates; D007210:Indoleacetic Acids; D011422:Propionates; D013463:Sulfuric Acid Esters; D014527:Uric Acid; C408690:4-cresol sulfate; C030737:indoleacetic acid; C041693:3-carboxy-4-methyl-5-propyl-2-furanpropionic acid; D007200:Indican; C030514:hippuric acid