title: Multi-site analytical evaluation of the Abbott ARCHITECT tacrolimus assay.
abstract: The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Tacrolimus immunoassay. Proficiency panels and specimens from a population of organ transplant recipients were analyzed in 6 clinical laboratories in Europe and the United States, and the results were compared with other methods. The ARCHITECT assay requires a whole blood specimen pretreatment step with methanol/zinc sulfate to precipitate protein and extract the drug, followed by a 30-minute immunoassay using anti-tacrolimus antibody-coated paramagnetic microparticles and an acridinium-tacrolimus tracer. The assay was free from hematocrit interference in the range 25%-55% and from interference by extremes of cholesterol, triglycerides, bilirubin, total protein, and uric acid. The total percent of coefficient of variations of the assay were 4.9%-7.6% at 3 ng/mL, 2.9%-4.6% at 8.6 ng/mL, and 3.1%-8.2% at 15.5 ng/mL. Limit of detection was < or =0.5 ng/mL and limit of quantification (LOQ) ranged from 0.69 to 1.07 ng/mL across the 6 sites (based on the upper 95% confidence interval concentrations). The 2007 European Consensus Conference on Tacrolimus Optimization recommended the use of assay methods with an LOQ around 1 ng/mL, based upon the need to measure trough tacrolimus blood concentrations precisely down to 3 ng/mL during low-dose tacrolimus regimens. Tacrolimus International Proficiency Testing Scheme samples were measured by the ARCHITECT immunoassay at 5 sites and showed an average bias of -0.28 to +0.85 ng/mL versus IMx Tacrolimus II immunoassay historical values and -0.21 to +0.68 ng/mL versus liquid chromatography/tandem mass spectrometry (LC-MSMS) Tacrolimus historical values. Method comparison studies were performed with the ARCHITECT Tacrolimus immunoassay on patient specimens with the following results: ARCHITECT Tacrolimus assay versus the Abbott IMx Tacrolimus II immunoassay (4 sites) yielded average biases between -0.94 and +0.26 ng/mL; ARCHITECT assay versus the Dade Dimension Tacrolimus immunoassay (2 sites) yielded average biases of -0.46 and +0.11 ng/mL; and ARCHITECT assay versus LC-MSMS methods at 2 sites yielded average biases of +0.51 and +1.63 ng/mL. Spearman correlation coefficients were >/=0.90 on all method comparisons. The ARCHITECT Tacrolimus assay is a semiautomated, robust, and highly sensitive immunoassay, representing an alternative approach for laboratories not equipped with LC-MSMS, and meets the 1 ng/mL recommendation of LOQ by the European Consensus Conference on Tacrolimus Optimization.
authors.affiliation: Cliniques universitaires St. Luc, Université catholique de Louvain, 10 Hippocrate Avenue, Brussels, Belgium. pierre.wallemacq@uclouvain.be
authors.forename: Pierre
authors.initials: P
authors.lastname: Wallemacq
authors.forename: Jean-Sebastien
authors.initials: JS
authors.lastname: Goffinet
authors.forename: Susan
authors.initials: S
authors.lastname: O'Morchoe
authors.forename: Thomas
authors.initials: T
authors.lastname: Rosiere
authors.forename: Gregory T
authors.initials: GT
authors.lastname: Maine
authors.forename: Myriam
authors.initials: M
authors.lastname: Labalette
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Aimo
authors.forename: Diana
authors.initials: D
authors.lastname: Dickson
authors.forename: Ed
authors.initials: E
authors.lastname: Schmidt
authors.forename: Reinhard
authors.initials: R
authors.lastname: Schwinzer
authors.forename: Rainer W
authors.initials: RW
authors.lastname: Schmid
mesh_terms: D002853:Chromatography, Liquid; D006801:Humans; D007118:Immunoassay; D007166:Immunosuppressive Agents / Q000097:blood*; D015203:Reproducibility of Results; D016559:Tacrolimus / Q000097:blood*; D053719:Tandem Mass Spectrometry
chemical_list: D007166:Immunosuppressive Agents; D016559:Tacrolimus