Therapeutic drug monitoring of cenobamate by a rapid HPLC-based determination

Cenobamate is a recently approved antiepileptic drug, which is highly efficacious as add-on treatment of hitherto drug-resistant focal-onset epileptic seizures. Here we developed and validated a simple and rapid method for determining cenobamate levels in human plasma. The approach is based on sample deproteination by addition of acetonitrile followed by isocratic reversed phase high performance liquid chromatography (HPLC) with UV-detection at 210 nm. The method is specific because none of 26 antiepileptic drugs (and five prominent metabolites thereof) interfered with the detection and quantification of cenobamate. Cenobamate plasma or serum levels were found to be stable over 12 days at room temperature. The method met the criteria for accuracy and precision set forth by the ICH guideline M10 on Bioanalytical Method Validation and Study Sample Analysis. The concentration range was explored to a lower limit of quantification (LLOQ) of 1 µg/mL. Samples from 131 real world patients were investigated: these covered a range of up to 39 µg/mL and were thus within the upper limit of quantification (ULOQ = 80 µg/mL). In addition, we observed a linear relation between administered dose and observed steady-state plasma concentration. The method is therefore suitable for routine therapeutic drug monitoring of cenobamate. • Cenobamate was recently approved for the treatment of drug-resistant epilepsy. • A simple and rapid method was developed for determining cenobamate levels in human plasma by HPLC. • The method was accurate, precise, specific and selective. • Cenobamate levels were determined in 131 patient samples. • The method is suitable for routine therapeutic drug monitoring of cenobamate.