Different top-down approaches to estimate measurement uncertainty of whole blood tacrolimus mass concentration values

Values of mass concentration of tacrolimus in whole blood are commonly used by the clinicians for monitoring the status of a transplant patient and for checking whether the administered dose of tacrolimus is effective. So, clinical laboratories must provide results as accurately as possible. Measurement uncertainty can allow ensuring reliability of these results. The aim of this study was to estimate measurement uncertainty of whole blood mass concentration tacrolimus values obtained by UHPLC-MS/MS using two top-down approaches: the single laboratory validation approach and the proficiency testing approach.

For the single laboratory validation approach, we estimated the uncertainties associated to the intermediate imprecision (using long-term internal quality control data) and the bias (utilizing a certified reference material). Next, we combined them together with the uncertainties related to the calibrators-assigned values to obtain a combined uncertainty for, finally, to calculate the expanded uncertainty. For the proficiency testing approach, the uncertainty was estimated in a similar way that the single laboratory validation approach but considering data from internal and external quality control schemes to estimate the uncertainty related to the bias.

The estimated expanded uncertainty for single laboratory validation, proficiency testing using internal and external quality control schemes were 11.8%, 13.2%, and 13.0%, respectively.

After performing the two top-down approaches, we observed that their uncertainty results were quite similar. This fact would confirm that either two approaches could be used to estimate the measurement uncertainty of whole blood mass concentration tacrolimus values in clinical laboratories.