Development and Clinical Validation of a Volumetric Absorptive Capillary Microsampling Method for Quantification of Mycophenolic Acid and Mycophenolic Acid Glucuronide in Kidney Transplant Recipients.

BACKGROUND

Mycophenolic acid (MPA) is a cornerstone of immunosuppressive treatment in kidney transplant recipients (KTRs). Traditional therapeutic drug monitoring for MPA is based on venous blood sampling. Finger-prick capillary microsampling is patient-friendly and enables limited sampling to predict the area under the curve. A liquid chromatography-tandem mass spectrometry assay to detect MPA and its metabolite mycophenolic acid glucuronide (MPAG) using volumetric absorptive capillary microsampling (VAMS) was developed and clinically validated.

METHODS

An assay based on VAMS and liquid chromatography-tandem mass spectrometry was validated bioanalytically and clinically. Agreement between dried microsamples and plasma samples was investigated in KTR on mycophenolate mofetil therapy. Paired microsamples and plasma samples were obtained before and at 0.5 and 2 hours postdosing. The samples were divided into development (75%) and validation (25%) datasets. Conversion from VAMS to plasma concentrations was established using a regression model, with at least 67% of paired samples required to fall within a mean relative difference of ±20%.

RESULTS

Twelve KTRs (median age: 49 years) provided 69 paired microsamples and plasma samples. For the VAMS method, the between-series mean accuracy was 90%-106% with a coefficient of variation <7% at concentrations of 0.25-32 mg/L (MPA) and 2.5-320 mg/L (MPAG). A conversion equation based on the regression model was applied and validated using an independent dataset. The mean relative differences between corrected microsamples and plasma samples were 1.9% for MPA and 2.7% for MPAG, with <5% outside ±20% for both analytes. Dried microsamples were stable for 3 months at ambient temperature.

CONCLUSIONS

The VAMS method demonstrated acceptable performance. MPA and MPAG can be reliably quantified using VAMS and are suitable for patient self-sampling in clinical pharmacokinetics studies of KTR.