Quantification of valproic acid in dried blood spots

Therapeutic drug monitoring (TDM) of the antiepileptic drug valproic acid (VPA) is recommended in patients with multiple drug therapy or with concomitant disabilities to ensure treatment efficacy and avoid adverse reactions in both adults and children. The use of sampling techniques compatible with home sampling, such as dried blood spot sampling could potentially facilitate this for patients. AIM. To assess the usefulness of a bioanalytical method for quantification of VPA in dried blood spots.

Quantification was based on liquid chromatography-mass spectrometry (LC-MS), both for the DBS method and the plasma-based reference method.

The method was validated in the range 10-1200 μmol/L. Total imprecision ranged from 4.9-8.9 (%CV) and accuracy was within ± 14%.

The validated method has potential for evaluation in therapeutic drug monitoring in combination with home sampling of DBS. The impact of spot size can be controlled through acceptance criteria and hematocrit in the range 30-60% can be accepted in sampling. Comparison of VPA levels between plasma and whole blood cannot be done without considering the blood-plasma ratio.