The Need for Standardization of Tacrolimus Assays

BACKGROUND: 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. METHODS: 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 spectrometry (EM-IDMS) at Laboratory of Government Chemists. RESULTS: 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 quality control CVs using 3 control levels were as follows: LC-MS low 3.8%–8.9%, medium 2.0%–6.0%, high 2.3%–6.3%; 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. CONCLUSIONS: 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.