Quantification of valproic acid in dried blood spots

Abstract

Background. 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. Materials and methods. Quantification was based on liquid chromatography-mass spectrometry (LC-MS), both for the DBS method and the plasma-based reference method. Results. 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%. Conclusion. 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.

Key Words::

• Blood-plasma ratio
• dried blood spot
• home sampling
• LCMS
• punching
• selected ion monitoring
• valproic acid

Acknowledgements

None

Declaration of interest: The authors report no conflicts of interest. The authors alone are responsible for the content and writing of the article.

This work was supported by grants awarded by Stockholm County Council (ALF 2011-0619 and ALF 2012-0413) and by the Swedish Research Council (Lars L. Gustafsson (VR 2011-3440 and VR 2011-7381).