Comparison of the reintroduced MEIA assay with HPLC-MS/MS for the determination of whole-blood sirolimus from transplant recipients.

Therapeutic monitoring with dosage individualization of sirolimus drug therapy is standard clinical practice for organ transplant recipients. For several years sirolimus monitoring has been restricted as a result of lack of an immunoassay. The recent reintroduction of the microparticle enzyme immunoassay (MEIA) for sirolimus on the IMx analyser has the potential to address this situation. This study, using patient samples, has compared the MEIA sirolimus method with an established HPLC-tandem mass spectrometry method (HPLC-MS/MS). An established HPLC-UV assay was used for independent cross-validation. For quality control materials (5, 11, 22 microg/L), the MEIA showed acceptable validation criteria based on intra- and inter-run precision (CV) and accuracy (bias) of <8% and <13%, respectively. The lower limit of quantitation was found to be approximately 3 microg/L. The performance of the immunoassay was compared with HPLC-MS/MS using EDTA whole-blood samples obtained from various types of organ transplant recipients (n = 116). The resultant Deming regression line was: MEIA =1.3 x HPLC-MS/MS + 1.3 (r = 0.967, S(y/x) = 1) with a mean bias of 49.2% +/- 23.1% (range, -2.4% to 128%; P<0.001). The reason for the large and variable bias was not explored in this study, but the sirolimus-metabolite cross-reactivity with the MEIA antibody could be a substantive contributing factor. Whereas the MEIA sirolimus method may be an adjunct to sirolimus dosage individualization in transplant recipients, users must consider the implications of the substantial and variable bias when interpreting results. In selected patients where difficult clinical issues arise, reference to a specific chromatographic method may be required.