Development of a liquid chromatography-tandem mass spectrometry method for assaying cenobamate in rat plasma. Issue 17 (8th November 2018)

• Record Type: Journal Article
• Authors: Oh, Ji-Hoon; Jeong, Jong-Woo; Ji, Yu-Geun; Shin, Yu-Mi; Lee, Kyeong-Ryoon; Hyung Cho, Kwan; Koo, Tae-Sung
• Is Part Of: Journal of liquid chromatography & related technologies. Volume 41:Issue 17/18(2018)
• Page Start: 992
• Page End: 997
• Publication Date: 2018-11-08
• Subjects: Cenobamate -- LC-MS/MS -- validation -- pharmacokinetics -- protein precipitation; Liquid chromatography -- Periodicals; Chromatographic analysis -- Periodicals; Separation (Technology) -- Periodicals; Biotechnology -- Periodicals; Chromatography, Liquid -- Periodicals; 543.8405
• DOI: 10.1080/10826076.2018.1547743
• Languages: English
• ISSNs: 1082-6076

Abstract

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: