Original ArticleVolumetric Absorptive Microsampling: A New Sampling Tool for Therapeutic Drug Monitoring of Antiepileptic DrugsD'Urso, Annachiara BiolSciD*; Rudge, James PhD†; Patsalos, Philip N. FRCPath, PhD‡,§; de Grazia, Ugo PhD*Author Information *Laboratory of Neurological Biochemistry and Neuropharmacology, Fondazione IRCCS Istituto Neurologico Carlo Besta, Milano, Italy; †Neoteryx LLC, Torrance, California; ‡UCL Queen Square Institute of Neurology, London; and §Therapeutic Drug Monitoring Unit, Chalfont Centre for Epilepsy, Chalfont St Peter, United Kingdom. Correspondence: Ugo de Grazia, PhD, Fondazione IRCCS Istituto Neurologico Carlo Besta, Via Celoria, 11, 20133 Milan, Italy (e-mail: [email protected]). A. D'Urso was supported by the Italian Ministry of Health Ricerca Corrente project 2018. The authors declare no conflict of interest. Informed consent and ethical approval were not required because the samples used were leftover from routine clinical therapeutic drug monitoring, and samples were anonymized. 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). Therapeutic Drug Monitoring: October 2019 - Volume 41 - Issue 5 - p 681-692 doi: 10.1097/FTD.0000000000000652 Buy SDC Metrics Abstract Background: Volumetric absorptive microsampling (VAMS) is a novel sampling technique for the collection of fixed-volume capillary blood. In this study, a new analytical method was developed and used to quantify 14 different antiepileptic drugs (AEDs) and 2 active metabolites in samples collected by VAMS. These data were compared with concentration measurements in plasma. Methods: The authors developed a selective and sensitive liquid chromatography–mass spectrometry (LC-MS/MS) assay to measure the concentrations of several AEDs in whole blood collected by VAMS, which were compared with a commercially available LC-MS/MS kit for AED monitoring in plasma. Drugs and internal standards were extracted from whole blood/plasma samples by a simple protein precipitation. Results: An LC-MS/MS method analyzing VAMS samples was successfully developed and validated for the determination of various AED concentrations in whole blood according to EMA guidelines for bioanalytical method validation. Extraction recovery was between 91% and 110%. No matrix effect was found. The method was linear for all drugs with R2 ≥0.989 in all cases. Intra-assay and inter-assay reproducibility analyses demonstrated accuracy and precision within acceptance criteria. Carry over and interferences were negligible. No volumetric HCT% bias was found at 3 different HCT values (35%–55%) with recovery being consistently above 87%. Samples are very stable at temperatures ranging from −20°C to 37°C and for a 4-month period. Leftover EDTA samples from 133 patients were tested to determine concentration differences between plasma and whole blood sampled by VAMS. The resulting difference varied less than 15% apart from those drugs with a blood/plasma ratio (R) different from 1. Conclusions: The assay allows for highly sensitive and selective quantification of several AEDs in whole blood samples collected by VAMS. The developed method is accurate and precise and free from matrix effects and volumetric HCT% bias. Copyright © 2019 Wolters Kluwer Health, Inc. All rights reserved.