A simple LC-MS method for the determination of iohexol and iothalamate in serum, using ioversol as an internal standard

Background: Chronic kidney disease (CKD) is diagnosed and explored through the determination of the glomerular filtration rate (GFR). Our goal was to develop a simple LC-MS method for the determination in serum of 2 popular GFR markers, contrast agents iohexol and iothalamate, for routine use and comparison studies between the two markers. A similar contrast agent, ioversol, was used as an internal standard and the method underwent a rigorous validation protocol based on beta-expectation tolerance intervals. Methods: We adapted the HPLC-UV method from Cavalier et al. to our LC-MS system. Data treatment for the validation was performed using Multiquant 3.0 (Sciex, Framingham, MA, USA) and e.noval 3.0 software (Arlenda, Liege, Belgium). Results: According to the validation results our method will give accurate and reliable results for concentrations ranging from 6.8 to 250 mu g/ml for iohexol and 6.15 mu g/ml to 250 mu g/ml for iothalamate. In our practice these intervals are sufficient to determine both compounds in most patient samples. Samples with higher detected concentrations can always be diluted into range. Conclusion: With its internal standard and extensive validation, our method is now ready for routine and clinical research use. (C) 2016 Elsevier B.V. All rights reserved.