Pharmacokinetics and brain uptake study of novel AMPA receptor antagonist perampanel in SD rats using a validated UHPLC-QTOF-MS method


    loading  Checking for direct PDF access through Ovid

Abstract

Graphical abstractHighlightsThe method shows high sensitivity, very good precision and accuracy with short run time.Simple protein precipitation as sample preparation approach with good recovery from plasma/brain homogenate.The method found to be linear from 0.4 to 400 ng/mL in both biomatrices.Application to pharmacokinetic and brain uptake study of perampanel in SD rats.Perampanel (PER) is a novel AMPA receptor antagonist for antiepileptic therapy and is prospective for the treatment of other neurological disorders. A highly sensitive and rapid UHPLC–QTOF-MS method was developed for the quantification of PER in plasma/brain homogenate of SD rat with alogliptin as an internal standard (IS). Chromatographic separation was carried out on an Acquity UPLC HSS Cyano column (100 mm × 2.1 mm, 1.8 μm) using gradient mobile phase consisting of 0.1% formic acid and acetonitrile at a flow rate of 0. 4 mL/min. Sample preparation was carried out by a simple protein precipitation method. The mass spectrometric analysis of target ions at [M + H]+m/z 350.1288 for PER and m/z 340.1779 for IS was monitored with extracted ion chromatography. The developed analytical method meets the US-FDA and EMA bioanalytical guidelines and was found to be precise, accurate, selective and rugged. It exhibited good sensitivity (0.4 ng/mL) and linearity over a range of 0.4–400 ng/mL in both the bio-matrices. The method was successfully applied to pharmacokinetics and brain uptake study of PER after oral administration to SD rats. The study results showed PER has penetrated the blood-brain barrier, brain to plasma ratio (Kp) was found to be 0.62 ± 0.05 and its rapidly eliminated from the brain.

    loading  Loading Related Articles