Volumetric Absorptive Microsampling (VAMS) for Therapeutic Drug Monitoring of Antiseizure Medications (ASMs) in...

Background: Volumetric absorptive microsampling (VAMS) is an emerging tool for therapeutic drug monitoring (TDM) of several drugs including antiseizure medications (ASMs). Here, we compared the concentrations of carbamazepine (CBZ), levetiracetam (LEV), lacosamide (LCS), topiramate (TPR) and the benzodiazepine (BZ) clobazam (CLB) in plasma and VAMS samples. Methods: VAMS samples were collected by fingerprick in pediatric patients followed at our center. Patients were also subjected to conventional venous blood sampling. Plasma and VAMS samples were analyzed by using a UHPLC-MS/MS validated kit for AEs and BZs (ClinMass LC-MS/MS Complete Kit^®). A cross-validation analysis was performed by using Spearman correlation (rho), Deming regression and Bland-Altman plots. Results: Two analytical methods for measuring selected AEs and BZs in VAMS samples were developed and validated in accordance with the ICH M10 guidelines. Based on Bland-Altman results, a satisfactory agreement was observed between VAMS and plasma for CBZ, LCS, TPR, LEV and N-CLB. Considering the absence of interchangeability between capillary blood and plasma levels for CBZ-Diol, -Epoxi and CLB, a blood to plasma ratio was used to convert VAMS values into estimated plasma concentrations. Comparison of estimated vs. observed plasma results showed a successful predictive performance for this conversion approach. Conclusions: A positive agreement between plasma and VAMS was found for CBZ, LCS, TPR, LEV and N-CLB. Conversely, a conversion factor based on blood to plasma ratio should be adopted to convert CBZ-Diol, -Epoxi and CLB VAMS results into estimated plasma concentrations. This study confirmed the utility of VAMS for TDM of selected ASMs in pediatric patients during routine clinical practice.