Tacrolimus Assay Comparison: Analytical and Operational Considerations for Immunoassay vs Mass Spectrometry Testing in a High Volume Clinical Laboratory.

BACKGROUND: Tacrolimus therapeutic drug monitoring is a routine and critical assay for managing transplant patients. Tacrolimus can be measured from whole blood samples via liquid chromatography-tandem mass spectrometry (LC-MS/MS) or immunoassay (IA). LC-MS/MS provides accurate parent drug quantification with minimal metabolite interference but requires expensive analyzers, highly trained staff, and is often a very manual process. Immunoassays offer faster, simpler workflows, but historically have been prone to significant cross-reaction with the drug's metabolites or other therapeutic drugs, leading to a falsely elevated result. Newer immunoassays show promising improvements in specificity.

METHODS: Using 73 residual patient samples, we compared our in-house LC-MS/MS tacrolimus assay to the Roche Elecsys® tacrolimus electrochemiluminescence immunoassay on the cobas® e801 analyzer. Comparative analysis was done with Deming regression and Bland-Altman comparison. Linearity, within-individual imprecision, and total imprecision post immunoassay implementation were also evaluated, along with changes and improvements to workflow and turnaround times (TAT).

RESULTS: The Roche Elecsys tacrolimus assay correlated well with our LC-MS/MS method (Deming regression equation: y = 1.004x + 0.4848). The bias was 0.52 ng/mL (an average of 8.1%) as determined by Bland-Altman comparison. When switching to the immunoassay we observed a 42%-51% improvement in TAT across the median, 75th percentile, and 90th percentile.

CONCLUSIONS: We observed excellent correlation between the Roche Elecsys tacrolimus assay on an e801 analyzer vs our in-house LC-MS/MS assay, with good precision and linearity across reportable ranges. Changing from mass spectrometry to tacrolimus immunoassay substantially improved our TAT and workflow.