The Need for Standardization of Tacrolimus Assays

Abstract

Owing to the lack of an internationally recognized tacrolimus reference material and reference method, current LC-MS and immunoassay test methods used to monitor tacrolimus concentrations in whole blood are not standardized. The aim of this study was to assess the need for tacrolimus assay standardization. We sent a blinded 40-member whole-blood tacrolimus proficiency panel (0-30 μg/L) to 22 clinical laboratories in 14 countries to be tested by the following assays: Abbott ARCHITECT (n = 17), LC-MS (n = 9), and Siemens Dade Dimension (n = 5). Selected LC-MS laboratories (n = 4) also received a common calibrator set. We compared test results to a validated LC-MS method. Four samples from the proficiency panel were assigned reference values by using exact-matching isotope-dilution mass spectrometr at LGC. The range of CVs observed with the tacrolimus proficiency panel was as follows: LC-MS 11.4%-18.7%, ARCHITECT 3.9%-9.5%, and Siemens Dade 5.0%-48.1%. The range of historical within-site QC CVs obtained with the use of 3 control concentrations were as follows: LC-MS low 3.8%-10.7%, medium 2.0%-9.3%, high 2.3%-9.0%; ARCHITECT low 2.5%-9.5%, medium 2.5%-8.6%, high 2.9%-18.6%; and Siemens/Dade Dimension low 8.7%-23.0%, medium 7.6%-13.2%, high 4.4%-10.4%. Assay bias observed between the 4 LC-MS sites was not corrected by implementation of a common calibrator set. Tacrolimus assay standardization will be necessary to compare patient results between clinical laboratories. Improved assay accuracy is required to provide optimized drug dosing and consistent care across transplant centers globally.