Traceability of immunosuppressant's mass concentration results obtained using different commercial calibrators

Due to the high inter-variability in immunosuppressants pharmacokinetics, therapeutic drug monitoring of these drugs is essential in order to minimize the risk of rejection after organ transplantation. Thus, results facilitated to clinicians by clinical laboratories for these drugs should be as reliable as possible. The knowledge of metrological traceability and performing compatibility studies can allow ensuring reliability of these results, mainly, when laboratories introduce substantial changes in their measurement procedures, e.g., when they change the calibration materials. The aim of this study was to investigate, as an example, the traceability of the calibrator's assigned values from two manufacturers (Recipe and Chromsystems) and to perform compatibility studies for sirolimus and tacrolimus.

Traceability was described according to ISO 17511. Compatibility studies, based on the CLSI EP029-A guideline, were performed verifying the trueness processing the ERM®-DA111a and ERM®-DA110a reference materials.

Traceability studies reveled that sirolimus and tacrolimus results were traceable to SI, except for sirolimus if Chromsystems' calibrators was used. Using Recipe's calibrators, the absolute relative biases and their expanded uncertainties were 1.23% and ±6.10% for sirolimus, and 1.41% and ±3.02% for tacrolimus. Furthermore, when Chromsystems' calibrators were used, these values were 12.2% and ±6.02% for sirolimus, and 2.64% and ±2.94% for tacrolimus.

Results reported a lack of traceability and compatibility of sirolimus' results when Chromsystems' calibrators was used. In order to avoid it, laboratories should only use calibrators with assigned values traceable to highest reference materials or, alternatively, perform a compatibility study and apply a bias correction factor.