Background The strong degree of structural similarity between everolimus and sirolimus (SRL) causes cross reactivity between them. The underestimation observed with the everolimus quantitative microsphere system (QMS) led many centres to opt for the sirolimus chemiluminescence magnetic microparticle immunoassay (CMIA) for therapeutic drug monitoring of everolimus.
Purpose The aim of this study was to compare the QMS assay with both CMIA and HPLC/MS assays (reference method).
Material and methods Blood samples of patients treated with everolimus from November 2014 to March 2015 were used in a correlation study between QMS and CMIA. Correlation between QMS and HPLC/MS, and CMIA and HPLC/MS was carried out using data reported by the external quality control programme, NEKAS, international proficiency testing scheme (St George’s University of London), from October 2010 to March 2015, testing target samples (blood to which a known amount of everolimus was added) and pooled samples (blood from patients). Passing–Bablock regression method, Bland–Altman plot and concordance correlation coefficient (CCC) were used in the statistical analysis.
Results The Bland–Altman plot showed that in target samples (n=60) there was underestimation of the real value, Target QMS=2.8 ng/mL (SD 1.96; −0.1 to 5.6), different from that observed in the two other assays: target-CMIA=−0.08 (SD 1.96; −1.41 to 1.24) and target HPLC/MS=0.12 (SD 1.96S: −0.92 to 1.17). In the pooled samples (n=20) results by QMS were closer to those reported by HPLC-MS than CMIA; HPLC/MS-QMS=0.06 (SD1.71; −1.6 to 1.96) and HPLC/MS-CMIA=−1.9 (SD 0.5; −4.3 to 1.96). Correlation between the two methods in 75 patient samples showed that both were equivalent: QMS=−0.32 + 0.94 CMIA, r=0.9054, CCC=0.8726 (95% CI 0.8095 to 0.9158).
Conclusion QMS tended to underestimate the real value and CMIA tended to overestimate it. It is possible that changing analytical method generates a significant decrease from the previous values but CMIA determined target samples with better accuracy than QMS, and therefore it is preferable to use CMIA to determine everolimus.
References and/or acknowledgements External quality control programme, NEKAS, international proficiency testing scheme.
No conflict of interest
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