title: Application of an isocratic methanol-based HPLC method for the determination of iohexol concentrations and glomerular filtration rate in patients with cirrhosis.
abstract: BACKGROUND
  Glomerular filtration rate (GFR) and mortality is more accurately determined by gold standard measures than serum creatinine-based estimates in cirrhosis. No formal validation of any gold standard method has been reported.
  
  
  METHODS
  An isocratic methanol-based method incorporating the reference standard iohexol-related compound C was developed and validated in 12 patients with cirrhosis by simultaneously determining GFR using iohexol and chromium-51 labelled ethylenediamine tetraacetic acid ((51)Cr-EDTA) clearance. Iohexol pharmacokinetics was also studied with the collection of blood and ascitic fluid at intervals following an iohexol bolus.
  
  
  RESULTS
  Triplicate assays produced a linear calibration curve (R (2)=0.99, N=5) over an iohexol concentration range of 23.6-755 µg/L. Mean (range) extraction recovery of iohexol from serum was greater than 95% (94-97%), with an intra-day coefficient of variation less than 3%. Twelve patients with cirrhosis with mean Child-Pugh score of 9 displayed a mean difference (bias) -1.3 mL/min/1.73 m(2) (-18 to +16) comparing iohexol with (51)Cr-EDTA. Iohexol equilibrated between blood and ascitic compartments after 4 h.
  
  
  CONCLUSIONS
  A simple, cheap, and accurate isocratic, methanol-based method for the determination of iohexol concentrations is described, validated according to Food and Drug Administration guidance. Iohexol demonstrated comparable performance with (51)Cr-EDTA in determining GFR. Delayed equilibrium of iohexol between blood and ascitic compartments suggests sampling beyond 4 h would improve accuracy of GFR determinations in patients with cirrhosis.
authors.affiliation: King's College Hospital, London, UK.
authors.forename: Andrew
authors.initials: A
authors.lastname: Slack
authors.forename: Michael
authors.initials: M
authors.lastname: Tredger
authors.forename: Nigel
authors.initials: N
authors.lastname: Brown
authors.forename: Benjamin
authors.initials: B
authors.lastname: Corcoran
authors.forename: Kevin
authors.initials: K
authors.lastname: Moore
mesh_terms: D000328:Adult; D000368:Aged; D001202:Ascitic Fluid / Q000473:pathology; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D002860:Chromium Radioisotopes / Q000008:administration & dosage; D003404:Creatinine / Q000097:blood; D005260:Female; D005919:Glomerular Filtration Rate; D006801:Humans; D007472:Iohexol / Q000008:administration & dosage / Q000493:pharmacokinetics*; D007677:Kidney Function Tests; D008103:Liver Cirrhosis / Q000097:blood* / Q000175:diagnosis / Q000473:pathology; D008297:Male; D008875:Middle Aged; D014481:United States; D014486:United States Food and Drug Administration
chemical_list: D002860:Chromium Radioisotopes; D007472:Iohexol; D003404:Creatinine
keywords: Clinical studies; chromatography; laboratory methods; liver disease