Abstract
Cenobamate is a candidate drug that is being evaluated in a phase 3 clinical trial as an epilepsy treatment. In the present study, we developed and validated a liquid chromatography-tandem mass spectrometry (LC-MS/MS) method for assaying cenobamate in rat plasma. Acetonitrile was used for plasma protein precipitation, whereas carisbamate was used as the internal standard. A Spursil C18 column and 10 mM ammonium formate and acetonitrile (60:40, v/v) were used for chromatographic separation. Detection was done using a triple quadrupole mass spectrometer by multiple reaction monitoring at transitions of m/z 268.06 ➜ 198.00 for cenobamate and m/z 216.09 ➜ 198.10 for carisbamate. The standard curve (r = 0.9946) was linear over a concentration range of 10 – 5000 ng/mL. Intra- and inter-day precision values were <14.97 and 14.86%, respectively, whereas intra- and inter-day accuracy values were less than 3.37 and 7.13%, respectively. Matrix effect, extraction recovery, and process efficiency were 98.59, 93.97, and 92.58%, respectively. Furthermore, cenobamate remained stable in rat plasma samples following three freeze-thaw cycles, storage at room temperature for 6 h, long-term storage at −20 °C for 4 weeks. The LC-MS/MS method was successfully used for studying the pharmacokinetics of cenobamate in rats.
Graphical Abstract
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Disclosure statement
No potential conflict of interest was reported by the authors.