Comparison between dried blood spot and plasma sampling for therapeutic drug monitoring of antiepileptic drugs in children with epilepsy: A step towards home sampling

Clin Biochem. 2017 May;50(7-8):418-424. doi: 10.1016/j.clinbiochem.2016.12.008. Epub 2016 Dec 24.


Objectives: To investigate if dried blood spots could be used for therapeutic drug monitoring of the antiepileptic drugs, carbamazepine, lamotrigine and valproic acid in children with epilepsy.

Methods: Fingerprick blood samples from 46 children at a neuropediatric outpatient clinic was collected on filterpaper at the same time as capillary plasma sampling. A validated dried blood spot liquid chromatography tandem mass spectrometry method for carbamazepine, lamotrigine and valproic acid was compared with the routine plasma laboratory methods. Method agreement was evaluated and plasma concentrations were estimated by different conversion approaches.

Results: Strong correlation was shown between dried blood spot and plasma concentrations for all three drugs, with R2 values>0.89. Regression analysis showed a proportional bias with 35% lower dried blood spot concentrations for valproic acid (n=33) and concentrations were 18% higher for carbamazepine (n=17). A ratio approach was used to make a conversion from dried blood spots to estimated plasma for these two drugs. Dried blood spot concentrations were directly comparable with plasma for lamotrigine (n=20).

Conclusions: This study supports that dried blood spot concentrations can be used as an alternative to plasma in a children population for three commonly used antiepileptic drugs with the possibility to expand by adding other antiepileptic drugs. Clinical decisions can be made based on converted (carbamazepine, valproic acid) or unconverted (lamotrigine) dried blood spot concentrations. Dried blood spot sampling, in the future taken at home, will simplify an effective therapeutic drug monitoring for this group of patients who often have concomitant disorders and also reduce costs for society.

Keywords: Conversion factor; Estimated plasma concentrations; Hematocrit; LC-MS/MS; Red blood cell/plasma ratio.

Publication types

  • Clinical Trial
  • Comparative Study

MeSH terms

  • Adolescent
  • Anticonvulsants / administration & dosage
  • Anticonvulsants / pharmacokinetics*
  • Child
  • Child, Preschool
  • Dried Blood Spot Testing*
  • Drug Monitoring / methods*
  • Epilepsy / blood*
  • Epilepsy / drug therapy*
  • Female
  • Humans
  • Male


  • Anticonvulsants