Long-term evaluation of analytical methods used in sirolimus therapeutic drug monitoring.

Results of therapeutic monitoring of sirolimus blood concentrations are assay and laboratory dependent. This study compared performance over time of the IMx microparticle enzyme immunoassay (MEIA), Architect chemiluminescent microparticle immunoassay (CMIA), and liquid chromatography with mass spectrometric detection (LC/MS/MS) as part of a proficiency testing scheme. Pooled samples from sirolimus-treated patients and whole-blood samples spiked with known quantities of sirolimus were assayed monthly between 2004 and 2012. When results of pooled patient samples were compared with LC/MS/MS, the MEIA assay showed an overall mean percent bias of -2.3% ± 11.2% that, although initially positive, became increasingly negative from 2007 through 2009. The CMIA, which replaced the MEIA assay, had a mean percent bias of 21.9% ± 12.3%, remaining stable from 2007 through 2012. Similarly, for spiked samples, the MEIA showed an increasingly negative bias over time vs. LC/MS/MS, whereas CMIA maintained a stable positive bias. Based on comparison of immunoassay measurements on individual patient samples, CMIA values were more than 25% higher than MEIA values. These results highlight the importance of continued proficiency testing and regular monitoring of sirolimus assay performance. Clinicians must be aware of the methodology used and adjust target levels accordingly to avoid potential effects on efficacy and toxicity.