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Common antiepileptic drugs have complex pharmacokinetic characteristics leading to fluctuation in their plasma levels at the same therapeutic doses. Therefore, antiepileptic drugs turn out to be among the most common medications for which therapeutic drug monitoring (TDM) is crucial. Indeed, TDM provides a realistic approach to adjust drug doses in epilepsy care based on plasma concentrations to optimize its clinical outcome. Perampanel (PER) is an antiepileptic drug used for the treatment of primary generalized tonic-clonic seizures in combination with other drugs, such as carbamazepine (CAR). Drug-drug pharmacokinetic interactions are very common in this combination, which makes TDM of PER essential. A selective, accurate, and precise bioanalytical method has been developed for the simultaneous determination of PER and CAR in human plasma for the purpose of TDM. Liquid-liquid extraction using ethyl acetate was applied for sample preparation, and diazepam (DZP) was the internal standard. The adopted method could successfully determine PER and CAR within their c.sub.max levels as the linearity range was 0.2-10 [micro]g/mL for PER and 5-100 [micro]g/mL for CAR. The chromatographic separation was achieved on a C8 column using acetonitrile, aqueous 0.1% glacial acetic acid (75 : 25, v/v) as a mobile phase in isocratic elution at a flow rate of 0.8 mL/min and an UV detection at 225 nm. The adopted method was validated according to EMA guidelines, and the results were within the acceptance criteria., Author(s): Said A. Hassan [sup.1] , Aya H. Helmy [sup.2] , Soheir A. Weshahy [sup.1] , Nadia F. Youssef [sup.2] , Badr A. El-Zeany [sup.1] Author Affiliations: (1) grid.7776.1, 0000 [...]