Abstract
Objectives
This study aims to evaluate the interchangeability between the Siemens Healthineers’ “EVRO” new affinity chrome-mediated immunoassay (ACMIA/EVRO) and Thermo Fisher Scientific’s “EVER” Quantitative Microsphere System (QMS/EVER) with Chromsystems’ CE-IVD-certified “MassTox” liquid-chromatography/tandem-mass spectrometry (LC-MS/MS) assay for the therapeutic drug monitoring of everolimus.
Methods
A single lot of reagent, calibrators and controls were used for each assay. A total of 67 whole blood samples (n=67) from patients receiving solid organ transplant were analyzed (n=31 with kidney transplant and n=36 with liver transplant); Passing-Bablok regression and Bland-Altman difference plot were used to evaluate bias and individual agreement; LC-MS/MS analysis was used to measure the actual concentrations of calibrators and controls compared to the assigned value.
Results
ACMIA/EVRO did not show any systematic bias compared to LC-MS/MS (intercept=0.244 ng/mL, 95% CI: −0.254 to 0.651 ng/mL). Nevertheless, significant proportional bias (slope=1.511, 95% CI: 1.420 to 1.619) associated to a combined bias of 44.8% (95% CI: 41.2–48.3%) was observed. Conversely, QMS/EVER did not show any bias at both systematic (intercept=−0.151 ng/mL, 95% CI: −0.671 to 0.256 ng/mL) and proportional level (slope=0.971, 95% CI: 0.895 to 1.074) with a non-statistically significant combined bias of −3.6% (95% CI: −8.4–1.1%). Based on a concentration of calibrators and controls above the assigned value for both the analytical methods, in the ACMIA/EVRO a correction which was approximately one-third of the correction for the QMS/EVER was observed.
Conclusions
ACMIA/EVRO but not QMS/EVER shows a lack of interchangeability with the CE-IVD-certified LC-MS/MS assay. We hypothesize that, as the ACMIA/EVRO uses an anti-sirolimus antibody, the under-corrected assigned value in the assay calibrators was not sufficient to reproduce the everolimus metabolites cross-reactivity occurring in real samples.
Acknowledgments
The authors thank B. Cortesi and P. Dulacchi for technical support. They thank Siemens Healthcare (Milan, IT) for providing ACMIA/EVRO materials.
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Research funding: None declared.
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Author contributions: All authors have accepted responsibility for the entire content of this manuscript and approved its submission.
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Competing interests: Authors state no conflict of interest.
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Informed consent: Not applicable.
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Ethical approval: The research related to human use has been conducted in accordance with all the most relevant national regulations, institutional policies and with the tenets of the Helsinki Declaration, and has been approved by the authors’ Institutional Review Board – approval nr. 0498/2021.
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Supplementary Material
The online version of this article offers supplementary material (https://doi.org/10.1515/cclm-2022-0699).
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