Simultaneous Measurement of Cyclosporine A, Everolimus, Sirolimus and Tacrolimus Concentrations in Human Blood by UPLC–MS/MS

Immunosuppressive drugs in whole blood: validation of a commercially available liquid chromatography/tandem mass spectrometry kit and comparison with immunochemical assays

“…In particular, the comparability was poor for both CSA and SIRO, for which the slopes of the Passing‐Bablock correlations were significantly higher than 1; moreover, for CSA, also the intercept was significantly higher than 0. For CSA the higher levels found by immunoassay are certainly due to the extensive metabolism of this drug and cross reactivity of the metabolites of CSA that cannot be separated from the parent compound . In our data the extent of overestimation was about 30%, and this is consistent with most previous works comparing immunoassays in general, and the ACMIA Dimension Siemens immunoassays in particular, with various LC/MS/MS assays.…”

“…For SIRO our results are very similar to those reported in previous studies, that compared the ACMIA Siemens immunoassay with in‐house LC/MS/MS assays; in particular, the package insert ACMIA Sirolimus reported a slope of the Passing‐Bablock correlations of 1.20 (95% CI 1.13–1.27) when 119 blood samples were analysed . In contrast, a recent work with a comparison between a CMIA Sirolimus reagent kit (Abbott Diagnostic, Abbott Park, IL, USA) and an in‐house LC/MS/MS method, performed with 62 blood samples, reported a better agreement without proportional or constant biases . The discrepancy between these results could be ascribed to the different immunoassays that were used.…”

“…For CSA the higher levels found by immunoassay are certainly due to the extensive metabolism of this drug and cross reactivity of the metabolites of CSA that cannot be separated from the parent compound . In our data the extent of overestimation was about 30%, and this is consistent with most previous works comparing immunoassays in general, and the ACMIA Dimension Siemens immunoassays in particular, with various LC/MS/MS assays. For SIRO our results are very similar to those reported in previous studies, that compared the ACMIA Siemens immunoassay with in‐house LC/MS/MS assays; in particular, the package insert ACMIA Sirolimus reported a slope of the Passing‐Bablock correlations of 1.20 (95% CI 1.13–1.27) when 119 blood samples were analysed .…”

“…The insert refers to a study performed with 201 blood samples, and reports an intercept of –0.26 (95% CI –0.14–0.0) and a slope of 1.04 (95% CI 1.00–1.07) for the Passing‐Bablock correlation . On the contrary, different results were previously reported when other immunoassays were applied . Again, the discrepancy between the studies could be ascribed to the different immunoassays that were used.…”

“…Our results are also in line with a very recent study applying the QMS assay to the analysis of 172 blood samples (from kidney, liver and hearth transplanted patients) and for which a Passing‐Bablock correlation slope of 0.95 (95% CI 0.889–1.000) and an intercept of –0.175 (95% CI –0.400–0.078) were found . Also a work performed using the Innofluor Certican kit (Seradyn Inc., Indianapolis, IN, USA) for the analysis of 73 blood samples showed that both proportional and constant biases were absent . Moreover, when our data were separated into kidney and liver transplant samples, to check whether differences associated with different organ transplants were present, in relationship to the possible influence of a different amount of metabolites, such as that possibly present in early liver transplanted patients, no significant difference was observed.…”