When mycophenolic acid (MPA) was originally marketed for immunosuppressive therapy, fixed doses were recommended by the manufacturer. Awareness of the potential for a more personalized dosing has led to development of methods to estimate MPA area under the curve based on the measurement of drug concentrations in only a few samples. This approach is feasible in the clinical routine and has proven successful in terms of correlation with outcome. However, the search for superior correlates has continued, and numerous studies in search of biomarkers that could better predict the perfect dosage for the individual patient have been published. As it was considered timely for an updated and

Tacrolimus and mycophenolic acid TDM for outpatient renal transplant recipients, based on abbreviated AUC collected with a DBS sampling device, is comparable to conventional TDM based on WB sampling. Patient training and guidance on good blood-spotting practices is essential to ensure method feasibility.

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Background: Drug nonadherence is one of the major challenges faced by resistant hypertension patients, and identification of this problem is needed for optimizing pharmacotherapy. Dried blood spot (DBS) sampling is a minimally invasive method designed to detect and determine the degree of nonadherence. In this study, a DBS method for qualifying 8 antihypertensive drugs (AHDs) and 4 active metabolites was developed and validated using ultra highperformance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS). Method: The DBS assay was validated analytically and clinically, in accordance with FDA requirements. Analytical validation was accomplished using UHPLC-MS/MS. For clinical validation, paired peak and trough levels of DBS and plasma samples were simultaneously collected and comparatively analyzed using Deming regression and Bland-Altman analyses. All concentrations below the set lower limit were excluded. Deming regression analysis was used to predict comparison bias between the collected plasma and DBS samples, with DBS concentrations corrected accordingly. Results: The UHPLC-MS/MS method for simultaneously measuring 8 AHDs and their metabolites in DBS, was successfully validated. With Deming regression no bias was observed in N = 1; constant bias was seen in N = 6 and proportional bias in N = 11 of the AHDs and metabolites. After correction for bias, only one metabolite (canrenone) met the 20% acceptance limit for quantification, after Bland-Altman analyses. In addition, amlodipine, valsartan, and [enalaprilate] met the 25% acceptance limit. Conclusions: A novel DBS assay for simultaneously qualifying and quantifying 8 AHDs and their metabolites, has been successfully developed and validated. The DBS assay is therefore a suitable method to detect drug nonadherence. However, with the exception of canrenone, the interchangeable use of plasma and DBS sampling to interpret drug quantities should be avoided.