Therapeutic Salivary Monitoring of Perampanel in Patients with Epilepsy Using a Volumetric Absorptive Microsampling Technique

Abstract

The objective of this study was to validate a novel assay using the volumetric absorptive microsampling (VAMS) technique combined with liquid chromatography coupled to tandem mass spectrometry (LC-MS/MS) for the determination of the antiseizure medication perampanel in saliva and its clinical applicability in patients with epilepsy. VAMS tips were loaded with 30 μL of saliva and dried for 60 min. Analytes were extracted with methanol. The supernatant was evaporated under a gentle stream of nitrogen and reconstituted with 60 μL of methanol. Separation and quantification were achieved on a monolithic column connected to a mass spectrometer. Calibration curves were linear between 0.5 and 300 ng/mL. Intra- and inter-day accuracy was within 85.6–103.2% and intra-day and inter-day precision did not exceed 12.1%. Perampanel was stable in samples collected by VAMS and stored under different storage conditions. The VAMS-LC-MS/MS method was validated according to internationally accepted criteria and tested in patients with epilepsy who were receiving a combination of perampanel and other antiseizure medications. The method showed adequate bioanalytical performances, holding great potential as an alternative strategy to support domiciliary TDM in patients with epilepsy treated with perampanel according to the simplicity of sample collection.

Development and Validation of HPLC-FLD Analysis of Perampanel in MEPS-Processed Rat Plasma Sample

“…All stock solutions were stored between 4 and 8 °C. There is variation in the limit of quantitation in the works showed by different authors using HPLC-UV (2.5-50 ng/mL) [3][4][5][6][7], HPLC-FLD (1-25 ng/mL) [3,[8][9][10], or LC-MS/MS (0.5-7.4 ng/mL) [8,[11][12][13][14][15][16][17][18], utilizing 10 to 1000 µL of plasma for sample processing and varied analytical conditions.…”

“…The literature describes a number of analytical techniques developed for the estimation of perampanel in human plasma, serum, and rat plasma. These techniques include HPLC-UV/PDA [3][4][5][6][7], HPLC-FLD [3,[8][9][10], LC-MS/MS [8,[11][12][13][14][15][16][17][18], UHPLC-QTOF-MS [19], capillary electrophoresis equipped with a fluorescence detector (CE-FLD) [20], HPTLC, and surface-enhanced Raman scattering (SERS) [21].…”