Automation in Busulfan Therapeutic Drug Monitoring: Evaluation of an Immunoassay on two Routine Chemistry Analyzers

Abstract

Background: Therapeutic drug monitoring (TDM) of busulfan is recommended for hematopoietic stem cell transplant recipients. Timely reporting of these TDM results is essential given the short administration period and the planned dose adjustments on day 2. The authors evaluated the performance of a new nanoparticle-based competitive immunoassay on two routine clinical chemistry analyzers and compared its performance to that of an in-house high-resolution mass spectrometry (HRMS) method.

Methods: The MyCare Oncology Busulfan Assay Kit (Saladax Biomedical) was applied on two routine clinical chemistry analyzers (Abbott Architect c8000 and Roche Cobas c502) with a linearity range of 187-2000 ng/mL. The study evaluation measured imprecision and accuracy, sample probe carry-over, and dilution integrity. Method comparison with liquid chromatography (LC)-HRMS was performed using samples from patients undergoing busulfan treatment.

Results: Within- and between-run coefficient of variations for both analyzers were ≤5.23% and ≤8.45%, respectively, across the busulfan concentration range. The obtained biases were ≤10.3%. Both analyzers met the acceptance criteria for sample probe carry-over and dilution integrity. Agreement between the immunoassay and LC-HRMS was high: 92% and 89% of the samples measured on Architect and Cobas, respectively, were within the ±15% limit compared to the corresponding LC-HRMS results.

Conclusions: Overall, good analytical performance and high agreement with LC-HRMS results were obtained for the immunoassay installed on both routine clinical chemistry analyzers. Therefore, this assay could be implemented as a valid alternative for LC methods in clinical laboratories on different open-channel clinical chemistry analyzers, resulting in shorter turn-around times for reporting busulfan TDM results with subsequent faster dosage adjustments.

Copyright © 2021 Wolters Kluwer Health, Inc. All rights reserved.

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Conflict of interest statement

The authors declare no conflict of interest.

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References

1. Malär R, Sjöö F, Rentsch K, et al. Therapeutic drug monitoring is essential for intravenous busulfan therapy in pediatric hematopoietic stem cell recipients. Pediatr Transpl. 2011;15:580–588.

2. Paci A, Veal G, Bardin C, et al. Review of therapeutic drug monitoring of anticancer drugs part 1—cytotoxics. Eur J Cancer. 2014;50:2010–2019.

3. Bartelink IH, Lalmohamed A, van Reij EM, et al. Association of busulfan exposure with survival and toxicity after haemopoietic cell transplantation in children and young adults: a multicentre, retrospective cohort analysis. Lancet Haematol. 2016;3:e526–e536.

4. Andersen AM, Bergan S, Gedde-Dahl T, et al. Fast and reliable quantification of busulfan in blood plasma using two-channel liquid chromatography tandem mass spectrometry: validation of assay performance in the presence of drug formulation excipients. J Pharm Biomed Anal. 2021;203:114216.

5. De Gregori S, Tinelli C, Manzoni F, et al. Comparison of two analytical methods for busulfan therapeutic drug monitoring. Eur J Drug Metab Pharmacokinet. 2021;46:155–159.

Show all 12 references