Multisite Analytical Evaluation of the Abbott ARCHITECT Cyclosporine Assay

• Published in: Therapeutic drug monitoring Vol. 32; no. 2; pp. 145 - 151
• Main Authors: WALLEMACQ, Pierre, MAINE, Gregory T, WERMUTH, Bendicht, SCHMID, Rainer W, BERG, Keith, ROSIERE, Thomas, MARQUET, Pierre, AIMO, Giuseppe, MENGOZZI, Giulio, YOUNG, Julianna, WONIGEIT, Kurt, KRETSCHMER, Robert
• Format: Journal Article
• Language: English
• Published: Hagerstown, MD Lippincott Williams & Wilkins 01-04-2010; Lippincott Williams & Wilkins Ovid Technologies; Lippincott, Williams & Wilkins
• Subjects: Antibody Specificity; Biological and medical sciences; Blood; Chemistry Techniques, Analytical - methods; Chemistry Techniques, Analytical - standards; Chromatography; Cyclosporine - blood; Drug Evaluation, Preclinical - methods; Drug Evaluation, Preclinical - standards; Drugs; Humans; Immune system; Immunoassay; Immunoassay - methods; Immunoassay - standards; Life Sciences; Mass spectrometry; Medical sciences; Pharmaceutical sciences; Pharmacology; Pharmacology. Drug treatments; cyclosporine; Evaluation; Calcineurin inhibitor; LC/MS/MS; method evaluation; HPLC chromatography; Liquid chromatography; Immunological method; immunoassay; Therapeutic drug monitoring; Mass spectrometry MS/MS; Ciclosporin; Immunosuppressive agent; "therapeutic drug monitoring"; "cyclosporine"; "method evaluation"; "LC/MS/MS"; "immunoassay"; therapeutic drug monitoring
• ISSN: 0163-4356; 1536-3694
• DOI: 10.1097/FTD.0b013e3181d46386

The objective of this study was to evaluate the analytical performance of the Abbott ARCHITECT Cyclosporine (CsA) immunoassay in 7 clinical laboratories in comparison to liquid chromatography/tandem mass spectrometry (LC/MS/MS), Abbott TDx, Cobas Integra 800, and the Dade Dimension Xpand immunoassay. The ARCHITECT assay uses a whole blood specimen, a pretreatment step with organic reagents to precipitate proteins and extract the drug, followed by a 2-step automated immunoassay with magnetic microparticles coated with anti-CsA antibody and an acridinium-CsA tracer. Imprecision testing at the 7 evaluation sites gave a range of total % coefficient of variations of 7.5%-12.2% at 87.5 ng/mL, 6.6%-14.3% at 411 ng/mL, and 5.2%-10.7% at 916 ng/mL. The lower limit of quantification ranged from 12 to 20 ng/mL. Purified CsA metabolites AM1, AM1c, AM4N, AM9, and AM19 were tested in whole blood by the ARCHITECT assay and showed minimal cross-reactivity at all 7 sites. In particular, AM1 and AM9 cross-reactivity in the ARCHITECT assay, ranged from -2.5% to 0.2% and -0.8% to 2.2%, respectively, and was significantly lower than for the TDx assay, in which the values were 3.2% and 16.1%, respectively. Comparable testing of metabolites in the Dade Dimension Xpand assay at 2 evaluation sites showed cross-reactivity to AM4N (6.4% and 6.8%) and AM9 (2.6% and 3.6%) and testing on the Roche Integra 800 showed cross-reactivity to AM1c (2.4%), AM9 (10.7%), and AM19 (2.8%). Cyclosporine International Proficiency Testing Scheme samples, consisting of both pooled specimens from patients receiving CsA therapy as well as whole-blood specimens supplemented with CsA, were tested by the ARCHITECT assay at 6 sites and showed an average bias of -24 to -58 ng/mL versus LC/MSMS CsA and -2 to -37 ng/mL versus AxSYM CsA. Studies were performed with the ARCHITECT CsA assay on patient specimens with the following results: ARCHITECT CsA assay versus LC/MSMS, average bias of 31 ng/mL; ARCHITECT versus the Dade Dimension assay (4 sites), average biases of -7 to -228 ng/mL; ARCHITECT versus AxSYM and TDx, average biases of -4 and -53 ng/mL, respectively. Spearman correlation coefficients were >or=0.89. The ARCHITECT CsA assay has significantly reduced CsA metabolite interference relative to other immunoassays and is a convenient and sensitive semiautomated method to measure CsA in whole blood.