Real-world evaluation of capillary microsampling for drug monitoring of anti-seizure medications.

OBJECTIVE: Capillary microsampling offers a minimally invasive alternative to venipuncture for therapeutic drug monitoring (TDM) of anti-seizure medications (ASMs). We evaluated the feasibility and reliability of volumetric absorptive microsampling (VAMS) and quantitative dried blood spot (qDBS) devices for ambulatory self-collection and at-home use in persons with epilepsy (PwE). METHODS: PwE attending the Epilepsy Centre of the IRCCS-Istituto delle Scienze Neurologiche di Bologna (Italy) were enrolled between October 2023 and October 2024. Participants performed supervised self-collection using VAMS and qDBS in ambulatory setting and at-home self-collection with VAMS devices. Sample quality, delivery success, and patient-reported outcomes (ease, pain, and clarity of instructions) were recorded. Carbamazepine, lacosamide, lamotrigine, and levetiracetam were quantified using a validated ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method. Reliability was assessed by comparing at-home VAMS with ambulatory VAMS and cross-validating qDBS with VAMS and venous plasma samples using Bland-Altman analysis and linear regression. RESULTS: A total of 105 PwE (66% female, mean age 41 years) performed at-home and ambulatory self-collection using VAMS and qDBS devices. Most at-home VAMS samples (88%) were received by the laboratory within 7 days, and 86.8% met high-quality criteria. For lacosamide, lamotrigine, and levetiracetam, we found strong correlations between at-home and ambulatory VAMS (Pearson's r ranging from .88 to .98) and low mean bias (<1.0 μg/mL). Conversely, carbamazepine showed lower reliability (r = .31; p = .49; bias = 2.05 μg/mL). Cross-validation of qDBS vs plasma confirmed good agreement (slope = .92, .63-1.21) with no significant systematic bias. Patient feedback indicated that self-collection was easy and minimally painful, although age>60 years impacted sampling quality, particularly for qDBS (p = .04). SIGNIFICANCE: VAMS-based self-collection is feasible and reliable for at-home TDM, provided that high-quality sampling is ensured. qDBS represents a reliable alternative for ambulatory monitoring. Future work should focus on optimizing sampling procedures for older adults and improving logistics for home-based microsampling.