Evaluation of the New Cyclosporine and Tacrolimus Automated Electrochemiluminescence Immunoassays under Field Conditions.

Background: Careful monitoring of the post-transplantation immunosuppressant drugs (ISDs) cyclosporine (CsA) and tacrolimus (TAC) in whole blood is essential to prevent adverse drug events. Immunoassays represent the most widely used methodology for therapeutic drug monitoring. In this study, the technical performance of the new automated electrochemiluminescence immunoassays (ECLIAs) for CsA and TAC measurement were assessed under field conditions.

Methods: Residual whole blood samples from patients undergoing CsA or TAC therapy following organ transplant were used to evaluate the assays at six independent laboratories across four countries. Experiments included within-run imprecision using PreciControl ISD controls and recovery of commercial external quality assurance (EQA) scheme samples. Both assays were compared with liquid chromatography-tandem mass spectrometry (LC-MS/MS), using methods routinely employed at each investigational site, as well as with an equivalent commercial chemiluminescent microparticle immunoassay (CMIA) and enzyme multiplied immunoassay (EMIT).

Results: Within-run imprecision testing gave coefficients of variation of ≤ 5% in the > 90.0 - 2000 ng/mL range for the CsA ECLIA and ≤ 4.2% in the 3.5 - 12 ng/mL range and ≤ 4.9% in the > 12 - 40 ng/mL range for the TAC ECLIA. EQA sample recovery by ECLIA gave a mean bias of 6.9% for CsA and 4.9% for TAC versus the spiked concentration or the mean LC-MS/MS value. Deming regression analysis of ECLIA method comparison to LC-MS/MS for all sites yielded a slope of 1.22, intercept 8.43 ng/mL and r = 0.97 for CsA and a slope of 1.22, intercept -0.51 ng/mL and r = 0.96 for TAC. Comparison with CMIA yielded a slope of 0.87, intercept 5.51 ng/mL and r = 0.97 for CsA and a slope of 0.98, intercept 0.12 ng/mL and r = 0.97 for TAC. Comparison with EMIT yielded a slope of 1.23, intercept -8.74 ng/mL and r = 0.96 for CsA.

Conclusions: The CsA and TAC ECLIA compare favorably with existing commercial immunoassays and with LC-MS/MS. They represent modern generation assays that meet the demands of monitoring drug concentrations in current immunosuppressive regimens. This study also highlights the importance of standardizing protocols and LC-MS/MS methods to give improved comparability between ISD assays.