ABSTRACT
Objective:To evaluate the proper blood collection time and calculation formula by measuring the iohexol plasma clearance as a representative of glomerular filtration rate at the same time of routine enhanced computed tomography (CT) examination.Methods:The prospective study method was applied, and 9 subjects with normal renal function, who admitted in Civil Aviation General Hospital from September 2018 to June 2019, were included. A single bolus of a standard dose (5 ml) (iodine concentration: 350 mgI/ml) was injected. The concentration of iohexol was measured from heparin plasma at fasting state of the subject and at nine different times after the injection, respectively. More than 24 hours after the injection of the standard dose, an enhanced CT-level dose (50 ml) of iohexol was injected to the subject and the concentration of iohexol was measured at similar time points as the standard dose. Using a multi-point method of a standard dose as the standard, the clearance rate was calculated by three kinds of formulas including Groth and Aasted formula, Jacobsson formula and Fleming formula with the single-point method to assess iohexol plasma clearance at 0.5 to 8.0 hours post injection of enhanced CT-level dose. The correlation consistency and accuracy of the multi-point method and the single-point method, as well as the dual-point method and the single-point method were compared, and the proper blood collection time and calculation formula of the single-point method at regular enhanced CT-level dose were evaluated. The correlation between the multi-point method and the single-point method, as well as the dual-point method and the single-point method were assessed using Pearson correlation coefficient; the consistency between the multi-point method and the single-point method, as well as the dual-point method and the single-point method were assessed by bias using mean±standard deviation ( SD) and 95% confidence interval ( CI) of mean difference and so on. We assessed the concordance of GFR using GFR±5% ( P5),±10% ( P10) and 1±30% ( P30) intervals. Results:Compared with the multi-point method, the mean deviation of iohexol plasma clearance obtained by the three single-point methods increased gradually from 5 hours after the injection of iohexol ( P<0.05). Compared with the multi-point method, only 3 h results, which was calculated by the Groth and Aasted formula, reached a P value greater than 0.05, a correlation coefficient of 0.938, a mean deviation of (-5.2±8.8) ml·min -1·1.73 m -2, and the concordances were 100% corresponding to P30,77.8% corresponding to P10, and 66.7% corresponding to P5; the 2, 3 and 4 hours results, which was calculated by the Jacobsson formula, reached P values greater than 0.05, when the blood collection time was 3 hours, the correlation coefficient was 0.938, and the mean deviation was the smallest, which was (1.5±6.2) ml·min -1·1.73 m -2, and the concordances were 100% corresponding to P30, 88.9% corresponding to P10, and 66.7% corresponding to P5; the 2 and 3 hours results, which was calculated by the Fleming formula, reached P values greater than 0.05, when the blood collection time was 2 h, the correlation coefficient was 0.956, and the mean deviation was the smallest, which was (-4.5±8.8) ml·min -1·1.73 m -2, and the concordances were 100% corresponding to P30, 77.8% corresponding to P10, and 55.6% corresponding to P5,Compared with the dual-point method, when Groth or Aasted formula was used, the mean deviation was the smallest at 3 hours, which was (-5.3±5.7) ml·min -1·1.73 m -2; when Jacobsson formula was used, the mean deviation was the smallest at 2 hours, which was (1.6±1.6) ml·min -1·1.73 m -2; when Fleming formula was used, and the mean deviation was the smallest at 2 hours, which was (-4.6±4.0) ml·min -1·1.73 m -2. Conclusion:At a regular enhanced CT-level dose, one blood collection can accurately measure the glomerular filtration rate, the proper time for blood collection can be 3 hours after iohexol injection, and the appropriate calculation formula can be Jacobsson formula.
ABSTRACT
Objective:To establish a method for iohexolquantification based on high performance liquid chromatography (HPLC) to measure the concentration of blood iohexolafterlow dose and contrast dose injection.Methods:Weperformed the method establishment and evaluation in this study. A HPLC-UV system (high performance liquid chromatography plus ultraviolet detector) was used to establish the method. The linearity, imprecision, recovery rate, limit of detection, lower limit of measuring interval and carryover of the method were evaluated. The stability of iohexol under different storage conditions, the differences of iohexolbetween serum and plasma concentrations, and the drug′s interference with the method were evaluated preliminarily. The single sample t test was used for the stability test of iohexolin samples, and the Wilcoxon symbol rank sum test was used for the comparison of iohexol concentrations between serum and plasma.Results:The linearity of iohexol ranging from 5 to 250 μg/ml ( R2=0.999 9) and from 250 to 4 000 μg/ml ( R2=0.999 8); when the concentration of iohexol was 20-3 000 μg/ml, the intra-and inter-assay coefficient of variation were 1.63% to 3.31% and 2.10% to 4.09%, respectively. The recovery rate was 94.17% to 106.13%; the limit of detection was 1 μg/ml and the lower limit of measuring interval was 5 μg/ml; it shows no carryover at the concentration of iohexol 4 000 μg/ml; after 48 hours at room temperature storage, the relative deviation of the concentration was -5.55% to +5.58%, after repeated freeze-thaw cycles 6 times at -80 ℃, the relative deviation of the concentration was -1.28% to+6.68%; there was no statistic difference between the measurement results between serum and plasma; valsartan and other drugs did not interfere with this methodsignificantly. Conclusion:Awide-range HPLC method for iohexolquantification has been established, which can stably and accurately detect the blood concentration of iohexol at low and contrast doses.