Background: Monitoring concentrations of tacrolimus in allograft recipients is considered the standard of care. Trough concentrations are regarded as a good surrogate for tacrolimus exposure. Dose adjustments, that are essential to maintaining tacrolimus levels within the therapeutic window and are critical in regulating the regimen, are made based upon test results. LC-MS/MS, considered the “gold-standard” for the measurement of tacrolimus, is not harmonized across laboratories. Here we demonstrate the harmonization of a commercial kit for tacrolimus through a proficiency testing survey. Harmonization of tacrolimus measurements should help facilitate the adoption of clinical practice guidelines and interpretation of results from multicenter trials. Methods: A 40 member blood panel (range ∼2.0 – 25 ng/mL tacrolimus) consisting of 20 pooled patient samples and 20 tacrolimus-supplemented samples was prepared and distributed to 7 laboratories in the U.S. and Europe. Testing was performed on a Waters ACQUITY® TQD system per the kit’s instructions. Four patient pools were prepared for value assignment (VA) by an exact-match isotope dilution mass spectrometry method (EM-IDMS), i.e., a reference measurement procedure (RMP). Results: Excellent agreement between all laboratories was observed for the proficiency testing panel (2.0 – 5.4% CV patient pools). For the 4 sample pools having VA by EM-IDMS (4.58, 7.66, 11.90, 19.82 ng/mL) the difference between this RMP and the mean measurements from the participating laboratories ranged from 0.6 – 4.4%, demonstrating excellent accuracy of the commercial assay across the therapeutic range. Conclusions: Standardization of tacrolimus assays is necessary to compare patient results between laboratories and to interpret consensus guidelines. The authors believe this is the first study to demonstrate harmonization of an LC-MS/MS assay for tacrolimus. This proficiency study provides information to clinicians regarding the comparability of tacrolimus patient results by LC-MS. The assay should be considered the method of choice for routine TDM and monitoring patients enrolled in tacrolimus drug trials. Values are accurate, precise and free from interferences, notably drug metabolites.

Joynes, C.: Employee, Waters Corporation: Immunosupressant TDM Kit. Mason, D.: Employee, Waters Corporation: Immunosuppressant TDM Kit. Champarnaud, E.: Employee, LGC Limited. Mussell, C.: Employee, LGC Limited. Calton, L.: Employee, Waters Corporation. Harter, L.: Employee, Waters Corporation. McKeown, D.: Employee, ASI International.

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