Evaluation of hematocrit-adjusted conversion strategies for mycophenolic acid and tacrolimus monitoring using volumetric absorptive microsampling in lung and renal transplant recipients

Objectives Mycophenolic acid (MPA) and tacrolimus (TAC) exhibit substantial pharmacokinetic variability, and volumetric absorptive microsampling (VAMS) offers a minimally invasive alternative for therapeutic drug monitoring (TDM). This study aimed to develop a VAMS-based method for MPA and TAC quantifications and systematically evaluate hematocrit (Hct)-adjusted conversion strategies. Methods Adult transplant recipients receiving mycophenolate mofetil or mycophenolate sodium were prospectively enrolled. Paired plasma (MPA), whole-blood (TAC), and VAMS samples were analyzed using validated LC–MS/MS method for simultaneous MPA and TAC quantification. Multiple Hct-adjusted conversion approaches for MPA were compared using Passing-Bablok regression, Bland-Altman analysis, and predictive performance metrics. Clinical applicability was assessed through scenario-based AUC estimation MPA AUC estimations under different sampling schemes. Results LC-MS/MS method for quantifying MPA and TAC in VAMS exhibited good linearity (R 2 0.99) and accuracy within 85–115% across validation ranges (10–20,000 ng/mL for MPA; 0.5–500 ng/mL for TAC). Formula A-ind (VAMS/1 – individual Hct) x f bpp , where f bpp represents the MPA protein binding fraction (0.97), achieved clinical agreement in 86% of samples for the conversion of MPA concentrations between VAMS and plasma, representing the most balanced between predictive reliability and operational feasibility. TAC concentrations from VAMS correlated strongly with whole blood values without requiring Hct correction. Clinical case applications showed that rich eight-point VAMS sampling enabled more accurate AUC estimations than conventional three-point schemes, further highlighting the advantages of using VAMS for MPA TDM. Conclusion This validated VAMS-based approach offers a minimally invasive and clinically applicable alternative to venous sampling for MPA and TAC monitoring. Incorporating individualized Hct adjustments improves predictive performance, supporting conditional integration of VAMS into routine TDM.