Verification of separate measurement procedures where analytical determinations influence the clinical interpretation of GFR: Iohexol quantitation by HPLC and LC-MS/MS

Background: The glomerular filtration rate (GFR) is monitored clinically to follow renal function of a patient. This is commonly performed using endogenous compounds, which estimate GFR (eGFR). However, several conditions exists which may confound or render the eGFR inaccurate. In such cases, it is appropriate to perform a procedure to directly measure GFR (mGFR). Iohexol plasma disappearance is a procedure to determine mGFR and is typically performed using bolus injection of contrast media followed by timed plasma collections. The iohexol plasma concentrations are referenced to the dose given and the elimination rate of iohexol is reflective of the mGFR. Therefore, analytical bias or interference in the iohexol analytical measurement procedure will directly impact the mGFR result. Methods: Plasma sample iohexol concentrations were measured using both high performance liquid chromatography-ultraviolet detection (HPLC-UV) and liquid chromatography tandem mass spectrometry (LC-MS/MS) measurement procedures. Results were compared on 50 patients where the mGFR was calculated from the iohexol plasma disappearance on two collection time points. Results: Bland-Altman analysis illustrated <1% mean bias when comparing iohexol concentration determinations from the measurement procedures. Passing-Bablok regression revealed y = 1.028x − 0.9420 (slope 95% CI: 1.011, 1.041; Y-intercept 95% CI: −1.606, −0.1638) when comparing LC-MS/MS to HPLC-UV. Conclusions: Comparison studies of the LC-MS/MS and HPLC-UV measurement procedures displayed a mean bias of <1% by Bland Altman analysis. Measurement of iohexol by LC-MS/MS and HPLC-UV produced similar results and suggests there should be minimal bias in concentration or computed mGFR solely due to the measurement procedure employed.