Rapid estimation of whole blood everolimus concentrations using architect sirolimus immunoassay and mathematical equations: comparison with everolimus values determined by liquid chromatography/mass spectrometry

Abstract

United States Food and Drug Administration (FDA) in 2010 approved the use of immunosuppressant drug everolimus, which requires therapeutic drug monitoring in whole blood. Taking advantage of structural similarity between sirolimus and everolimus we attempted to rapidly estimate everolimus concentration from apparent sirolimus concentration obtained by using Architect sirolimus immunoassay and mathematical equations (both polynomial and linear). Mathematical equations were derived by curve-fitting methods based on observed apparent sirolimus concentration and true everolimus concentration determined by a liquid chromatography combined with mass spectrometry (LC/MS) method using eight everolimus standards (concentration range 1-30 ng/mL) prepared in whole blood. In order to determine the validity of our approach, we analyzed 12 specimens from patients receiving everolimus using both Architect sirolimus assay and LC/MS method. We observed good correlation between calculated everolimus values and true everolimus values as determined by LC/MS. However, if a patient is switched from sirolimus to everolimus, then sirolimus immunoassay can roughly estimate everolimus concentration plus any residual sirolimus present in whole blood and it is not possible to calculate everolimus concentration.