Clinical validation of a patient‐friendly saliva microsampling approach to monitor perampanel levels in people with epilepsy

Perampanel (PER) is a third-generation antiseizure medication (ASM) with a well-established concentration-effect relationship. Saliva represents a non-invasive alternative to plasma for therapeutic drug monitoring (TDM) of PER, as it reflects the free plasma fraction. Volumetric absorptive microsampling (VAMS) enables standardized, patient-friendly saliva collection. This study aimed to clinically validate saliva-VAMS by directly comparing it with conventional liquid saliva sampling for PER quantification. In a prospective study, saliva was collected from 11 people with epilepsy receiving PER therapy (dose range = 2-10 mg/day) using both VAMS and conventional saliva sampling. PER concentrations were measured by liquid chromatography coupled with tandem mass spectrometry and compared using repeated measures Bland-Altman analysis and Lin's concordance correlation coefficient to evaluate agreement between methods. PER concentrations measured in saliva-VAMS showed excellent agreement with those obtained from conventional saliva sampling, with mean bias of -0.126 ng/mL (95% confidence interval = -0.582 to 0.330). No relevant constant or proportional bias was observed, and limits of agreement were within predefined acceptance criteria. Concordance between methods was high, supporting analytical equivalence. The demonstrated interchangeability between saliva-VAMS and conventional saliva sampling supports adoption of saliva-VAMS in clinical TDM workflows, enabling standardized fixed-volume collection, simplified storage/transport, and potential home-based sampling for remote dose optimization of PER and potentially other ASMs.