ORIGINAL ARTICLE Dried Blood Spot Self-Sampling by Guardians of Children With Epilepsy Is Feasible: Comparison With Plasma for Multiple Antiepileptic Drugs Camilla Linder, MSc,*† Mirja Neideman, MSc,‡ Katarina Wide, MD, PhD,§¶ Mia von Euler, MD, PhD,†║ Lars L. Gustafsson, MD, PhD,*† and Anton Pohanka, PhD*† Background: Dried blood spot (DBS) is an attractive matrix alternative to plasma for the measurement of antiepileptic drug concentrations with the possibility of self-sampling at home. The aim of this study was to evaluate whether DBS concentrations from a children population could be used as an alternative to plasma concentrations in a clinical routine laboratory. Methods: Children with epilepsy using carbamazepine (CBZ), lamotrigine (LTG), levetiracetam (LEV), or valproic acid (VPA) had capillary blood collected for routine plasma analysis. DBS samples were collected by guardians or nurses, and the quality of sampling was compared between the groups. DBS samples were analyzed with liquid chromatography–tandem mass spectrometry methods and plasma samples with immunochemical methods. In the comparison between DBS and plasma concentrations, previously analyzed sample data were pooled with data in this study and resulted in 190 comparison pairs. A bioanalytical cross-validation according to European Medicines Agency was performed. Clinicians evaluated the results to understand if a DBS concentration was linked to a dif- ferent clinical dose recommendation for the patient in comparison with plasma concentrations. Results: Comparison of DBS sample quality showed that 2.3% of the capillary DBS collected by guardians were rejected and 8.0% of the capillary DBS collected by nurses. For DBS, a conversion factor of 0.85 for CBZ and 1.65 for VPA was applied for the comparison with plasma. LTG and LEV results were directly comparable. In the cross-validation, 88% of CBZ, 75% of LTG, 74% of LEV, and 94% of VPA comparisons were within 20% of the difference of the mean, although LEV had a few major differences (+31% to 240%). In 4 of the 190 comparisons, the clinical evaluation indicated a risk of con- flicting decisions regarding the need for dose adjustment when using DBS concentrations. However, the risk of negative patient outcomes was considered negligible. Conclusions: Our study demonstrates that a combination of bioanalytical cross-validation and clinical evaluation is an effective way to describe the applicability of DBS as an alternative to plasma, taking into account how therapeutic drug monitoring is used in specific patient groups. For LTG, converted CBZ and VPA, DBS is a feasible alternative for self-sampling at home. DBS for LEV can only be recommended for nonadherence queries due to the high variability of the plasma/DBS concentration ratios. Key Words: anticonvulsants, clinical validation, LC-MS/MS, self- sampling, TDM (Ther Drug Monit 2019;41:509–518) INTRODUCTION Dried blood spot (DBS) is an alternative sampling strategy for therapeutic drug monitoring (TDM). A simple finger prick and the subsequent collection of blood drops on a filter paper allows for sampling in the patient’s home. 1,2 This procedure is helpful for patients with difficulties travel- ling and children with epilepsy (often with concomitant diag- noses) and their guardians, as it can save time, money, and reduce stress. In addition, DBS enables repeated sampling in patients with complicated antiepileptic drug (AED) therapy. This study investigated the feasibility of DBS self-sampling by guardians for the routine TDM of common AEDs in chil- dren with epilepsy. As patients are becoming more involved in their treatment, self-sampling at home has increased during the past decade. 3 Self-management and self-monitoring is a safe alternative in oral anticoagulant therapy. 4 A recent study con- cluded satisfactory results of self-sampling at home when monitoring tacrolimus and creatinine levels with DBS, col- lected by guardians of pediatric transplant recipients. 5 Today’s sensitive and specific liquid chromatography– tandem mass spectrometry (LC-MS/MS) instrumentation and microsampling makes DBS a reliable matrix for TDM. 6,7 Received for publication October 22, 2018; accepted December 10, 2018. From the *Division of Clinical Pharmacology, Department of Laboratory Med- icine, Karolinska Institutet; †Department of Clinical Pharmacology, Karo- linska University Hospital; ‡Department of Pediatrics, Sachsska Children’s Hospital; §Department of Clinical Science, Technology and Intervention (CLINTEC), Karolinska Institute; ¶Department of Pediatrics, Karolinska University Hospital; and ║Departments of Clinical Science and Education, Södersjukhuset and Medicine, Solna, Karolinska Institute, Stockholm, Sweden. L. L Gustafsson received a grant from Swedish Research Council (VR-2011/ 3440) and from Stockholm Healthcare Region (ALF/SLL2016/ 0608), and K. Wide received a grant from Margaretahemmet Foundation and The Swedish Epilepsy Association. The remaining authors declare no conflict of interest. Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal’s Web site (www.drug-monitoring. com). Correspondence: Camilla Linder, MSc, Department of Clinical Pharmacol- ogy, C1:68, Karolinska University Hospital, Stockholm SE-141 86, Sweden (e-mail: camilla.linder@sll.se). Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved. Ther Drug Monit  Volume 41, Number 4, August 2019 509 Copyright © 2019 Wolters Kluwer Health, Inc. Unauthorized reproduction of this article is prohibited.