Evaluation of Volumetric Absorptive Microsampling as an Alternative Matrix for Therapeutic Drug Monitoring of Antiseizure Medications: A Robust Clinical Validation Study

Background: Microsampling techniques, such as volumetric absorptive microsampling (VAMS), are gaining popularity for therapeutic drug monitoring (TDM) of various drugs. VAMS is especially useful for conditions that affect more vulnerable patients, such as children and older patients. Epilepsy is a chronic disease that is treated with antiseizure medications (ASMs) and must be monitored throughout the patient's lifetime. However, before their use in clinical settings, clinical validation must be performed to assess their suitability and determine the correlation between VAMS concentrations and plasma concentrations for which therapeutic ranges are established. Methods: Paired VAMS, plasma, and whole blood (WB) samples were collected and analyzed from 159 patients treated with at least 1 of the 8 ASMs studied. Clinical validation was performed for levetiracetam (LEV) and valproic acid (VPA) with >60 positive samples, and preliminary clinical validation was performed for lamotrigine (LTG) with >30 samples using Passing–Bablok and Bland–Altman analyses. Results: For all 3 ASMs, concentrations in VAMS correlated well with both plasma and WB concentrations (Pearson ρ > 0.98). The analytical requirements established by the European Medicines Agency and Food and Drug Administration were met when comparing VAMS and plasma concentrations. However, in some cases, a correction of the concentrations was required for comparison with WB. Conclusions: The results demonstrate a good equivalence of VAMS and plasma concentrations. This renders VAMS a suitable sample for the TDM of LEV, VPA, and possibly LTG.