Evaluation of the Abbott ARCHITECT i2000 sirolimus assay and comparison with the Abbott IMx sirolimus assay and an established liquid chromatography-tandem mass spectrometry method

Background: Sirolimus is indicated for prophylaxis treatment to prevent solid organ rejection. Due to intrapatient and interpatient variabilities in pharmacokinetics, risk of concentration-related toxicity, risk of noncompliance, and a high likelihood of drug-drug interactions, therapeutic drug monitoring of sirolimus is essential. There are several methodologies used clinically to monitor sirolimus, ranging from immunoassay to tandem mass spectrometry, each with potential strengths and limitations. The purpose of our study was to validate the Abbott ARCHITECT i2000 sirolimus assay. Materials and Methods: The Abbott ARCHITECT i2000 sirolimus assay was evaluated for linearity, limit of detection, limit of quantification, imprecision, common interferences, and accuracy. Accuracy was compared with the Abbott IMx sirolimus assay and with an established liquid chromatography-tandem mass spectrometry method. Stability of sirolimus when specimens were stored frozen (-20°C) or refrigerated (2-8°C) and degree of crossreactivity of the i2000 with everolimus were also evaluated. Results: The ARCHITECT i2000 assay demonstrated good linearity, low imprecision, and was free of common interferences. Results for both immunoassay methods were biased slightly high, compared with those of liquid chromatography-tandem mass spectrometry. Sirolimus was stable when samples were stored either refrigerated or frozen. However, the results generated with samples stored refrigerated had an increase in scatter on the regression plots compared with those generated for samples that were stored frozen, indicating that extraction of the drug may be incomplete, particularly with the Abbott IMx assay. In addition, statistical performance indices suggest that the agreement between the ARCHITECT i2000 and Abbott IMx was better for frozen patient samples. The ARCHITECT i2000 and the Abbott IMx methods both exhibited a >100% crossreactivity with everolimus. Conclusions: The Abbott ARCHITECT i2000 instrument demonstrates reasonable sensitivity, precision, and accuracy for supporting routine therapeutic drug monitoring of sirolimus with either refrigerated or frozen whole blood collected from patients who are not comedicated with everolimus.