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Application of an Isocratic Methanol-Based HPLC Method for the Determination of Iohexol Concentrations and Glomerular Filtration Rate in Patients With Cirrhosis

Application of an Isocratic Methanol-Based HPLC Method for the Determination of Iohexol Concentrations and Glomerular Filtration Rate in Patients With Cirrhosis

Andrew Slack, Michael Tredger, Nigel Brown, Benjamin Corcoran, Kevin Moore

Ann Clin Biochem. 2014 Jan;51(Pt 1):80-8.

PMID: 23847035

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.
Conclusion:
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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
AP31127807	Iohexol Related Compound A		31127-80-7	Price
AP76820343	Iohexol Related Compound C		76820-34-3	Price

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