External Validation of a Limited Sampling Strategy for the Estimation of Mycophenolic Acid Exposure Between Different Assay Methods: PETINIA and HPLC Methods.

Introduction: A limited sampling strategy (LSS) for estimating the area under the plasma concentration-time curve (AUC) of the immunosuppressant mycophenolic acid (MPA) is used for therapeutic drug monitoring (TDM) in clinical practice. Our study delves into the applicability of the MPA AUC LSS, originally developed using particle-enhanced turbidimetric inhibition immunoassay (PETINIA) measurements, to those obtained via high-performance liquid chromatography with ultraviolet detection (HPLC-UV).

Methods: We developed an LSS for estimating MPA AUC based on PETINIA measurements in 32 adult kidney transplant patients who were receiving mycophenolate mofetil. Validation of this strategy was conducted in an additional 14 adult kidney transplant patients (validation sets) through measurements obtained by both PETINIA and HPLC-UV. Predictive performance was assessed using mean absolute error (MAE), root mean squared error (RMSE), and "good guess" defined as predicted AUC within observed AUC ± 15%.

Results: The three time point equation (0, 2, and 6 h) emerged as optimal for estimating MPA AUC, balancing predictive performance and usefulness in clinical settings. In validation sets, the coefficient of determination for observed versus predicted AUC was consistent between PETINIA (0.978) and HPLC-UV (0.958) measurements. Comparable MAE, RMSE, and "good guess" outcomes were observed for PETINIA (6.4%, 8.1%, and 85.7%, respectively) and HPLC-UV (7.6%, 9.4%, and 85.7%, respectively) measurements.

Conclusion: Our findings support the application of the MPA AUC LSS, originally developed using PETINIA measurements, to those obtained via HPLC-UV.