Preliminary Analytical Evaluation of the Automated Cobas i601 LC-MS/MS System for Immunosuppressant Quantification in a Clinical Laboratory.

Abstract

INTRODUCTION: Therapeutic drug monitoring (TDM) of immunosuppressive drugs is essential to maintain concentrations within narrow therapeutic windows and minimize toxicity. Automated liquid chromatography-tandem mass spectrometry (LC-MS/MS) platforms can combine the analytical specificity of mass spectrometry with workflow efficiency suitable for routine laboratories. OBJECTIVES: To preliminarily evaluate the analytical performance of the Cobas i601 automated LC-MS/MS system for quantifying tacrolimus, cyclosporine, everolimus, and sirolimus and to compare results with routine immunoassays and an LC-MS/MS method for sirolimus. METHODS: Imprecision, bias, and linearity were assessed according to the Clinical Laboratory Standards Institute (CLSI) EP10-A3 standard using quality-control materials. Method comparison and bias estimation versus the Dimension EXL 200 immunoassays and an LC-MS/MS technique for sirolimus followed the CLSI EP09-A3 standard. Regression analyses and predicted biases at therapeutic range concentrations were compared with allowable limits. RESULTS: The Cobas i601 showed good precision and linearity, meeting manufacturer specifications. The highest coefficients of variations for tacrolimus, everolimus, cyclosporine, and sirolimus were 4.0%, 4.7%, 3.6%, and 4.8%, and the maximum EP10-A3 biases were -7.4%, -3.9%, 4.7%, and 5.4%, respectively. In the method comparison, tacrolimus, everolimus, and cyclosporine showed substantial negative biases versus immunoassays (-22.7%, -38.9%, and -37.5%), exceeding allowable limits. Sirolimus exhibited smaller positive bias relative to the LC-MS/MS method (12.5%). Interchangeability between the methodologies cannot be assumed. CONCLUSION: The Cobas i601 provides reliable automated LC-MS/MS quantification of immunosuppressants, with good precision and linearity. Method-dependent biases highlight the need for careful interpretation during technology transitions. The Cobas i601 shows strong potential for routine LC-MS/MS implementation in TDM in clinical laboratories. This study evaluated the Cobas i601, an automated system for measuring immunosuppressive drugs in blood. The system showed high precision and reliability. Some differences were observed compared with the tests currently used, highlighting the need for careful interpretation when changing methods. Overall, the Cobas i601 could improve patient care by providing more accurate drug measurements while simplifying laboratory workflow.

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