Evaluation of the Novel Methotrexate Architect Chemiluminescent Immunoassay: Clinical Impact on Pharmacokinetic Monitoring

Background: Fluorescence polarization immunoassay (FPIA) has probably been the most widely used technique for the determination of methotrexate (MTX) concentrations in clinical laboratories. After its replacement by a novel architect chemiluminescent microparticle immunoassay (CMIA), it is essential to verify that there are no differences between the methods that can induce an error in leucovorin rescue with dire consequences for the patient. The objective of our study was to compare plasma/serum MTX measurements between CMIA and FPIA (reference method in this study) in the work conditions of a clinical pharmacokinetics unit to determine whether any difference would affect clinical decisions on the management of this drug. Methods: FPIA on TDx/FLx and CMIA on Architect ci8200 were simultaneously used to evaluate 127 clinical samples. Within-run (20 repetitions on same day) and between-run (20 repetitions on different days) imprecision was evaluated using 6 control samples provided by the manufacturer and diluting 2 of them by 50% for 0.03 and 0.22 mmol/L, respectively. The Passing-Bablok regression method, Bland-Altman plot, and concordance correlation coefficient (CCC) were used in the statistical analysis. Results: Within-run imprecision was <5% (3.6%-4.39%) and between-run imprecision,11% (2.42%-10.65%). Between-assay correlation for the studied concentration range (0.05-250 mmol/L) was CMIA = 20.026 + 1.033 FPIA (n = 127), r = 0.9963, and CCC = 0.9946. For samples <1.5 mmol/L (nondiluted) included in the assay calibration curve, the correlation was CMIA = 20.009 + 0.955 FPIA (n = 54), r = 0.9819, and CCC = 0.9807. No significant difference was observed between the measurements by the 2 assays, given that the 95% confidence interval of the ordinate at the origin included "0" (20.020 to 0.0007), and the 95% confidence interval of the slope included 1 (0.923-1.020). The interchangeability of these assays was confirmed by Bland-Altman plot results, which showed a mean difference insignificant at concentrations <10 mu mol/L. Conclusions: The correlation between methods was excellent, and Passing-Bablok regression analysis detected no virtually difference in their results. Utilization of the CMIA-Architect assay to measure MTX concentrations would therefore not affect clinical decisions on MTX management, supporting its employment in routine MTX monitoring.