LC-MS/MS assay for the therapeutic drug monitoring of perampanel in children with drug-resistant epilepsy

Abstract Perampanel (PER) is the first clinically available selective antagonist of α -amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor approved globally for treatment epilepsy. Studies have recently underlined significant association between dose-exposure-effect-adverse events PER in patients with epilepsy, so therapeutic drug monitoring (TDM) critical clinical practices, especially pediatric drug-resistant Due to several limits previous published analytical methods, herein, we describe development and validation a novel liquid chromatography tandem mass spectrometry (LC-MS/MS) method human plasma samples. Protein precipitation by acetonitrile containing PER-d5 as internal standard was applied sample clean-up. Formic (FA, 0.2 mM) both aqueous water were used mobile phases analyte separated an isocratic elution. Qualification quantification performed under positive electrospray ionization (ESI) mode using m/z 350.3 → 219.1 355.3 220.0 ions pairs transitions PER-d5, respectively. Potential co-medicated anti-seizure medications (ASMs) no interference analysis. Calibration curves linear concentration range 1.00–2,000 ng mL −1 PER. The intra- inter-batch precision, accuracy, recovery, dilution integrity, stability all within acceptable criteria matrix effect or carryover found. This then successfully implemented on TDM Chinese children We firstly confirmed apparent inter- intra-individual variabilities potential drug-drug interactions concomitant ASMs occurred patients, which also line studies other race.