Clinical evaluation of a dried blood spot method for determination of mycophenolic acid in renal transplant patients

• Mycophenolic acid is widely used in immunosuppressive therapy after renal transplantation.
• Therapeutic drug monitoring of mycophenolic acid is usually done in plasma, with several sampling times to calculate AUC.
• Mycophenolic acid can be measured in dried blood spots by HPLC-DAD.
• Plasma concentrations of mycophenolic acid can be estimated after measurement in dried blood spots and mathematical correction.
• Individual or mean hematocrit values are necessary to estimate plasma mycophenolic acid concentrations from DBS measurements.

ObjectivesThe aim of this study is to evaluate the clinical application of dried blood spots (DBS) sampling in renal transplant patients under mycophenolic acid (MPA) immunosuppression, comparing measurements performed in paired plasma and DBS samples.Design and methods77 paired DBS and plasma samples were obtained from 19 renal transplant patients. MPA was measured in both matrices by HPLC-DAD. Estimated plasma concentrations (EPC) were calculated from DBS concentrations (DC) using the formula EPC = DC/[1 − (Hct/100)], using either individual or mean hematocrit (Hct). Agreement between methods was evaluated using Passing–Bablok regression and Bland–Altman difference plots.ResultsMPA concentrations in DBS were in mean 60.7% of those measured in plasma. EPC calculated from DBS and patient's individual Hct presented a high correlation with blood plasma (r = 0.9862), and comparable absolute values (slope 1.0563 and intercept − 0.0739), being in mean 102.2% of the measured plasma concentrations. EPC can also be calculated with the mean Hct of the group of patients, with similar results.ConclusionsDBS sampling can be used for TDM of MPA in a clinical setting, employing conventional HPLC equipment, presenting similar results to plasma samples after a proper mathematical treatment. Moreover, due to its intrinsic stability and handling safety, DBS sampling can be considered a useful alternative especially in developing countries where sample logistics could be a major difficulty.