Quantification of mesembrine and mesembrenone in mouse plasma using UHPLC-QToF-MS: Application to pharmacokinetic study

Sceletium tortuosum is widely used throughout the world as an herbal supplement in the treatment of anxiety and stress. The two main pharmacologically active alkaloids are reported to be mesembrenone and mesembrine. Despite the wide use and reports in the literature confirming the pharmacological activities of Sceletium extract, there are no reports of in vivo pharmacokinetic studies of its active ingredients or analytical methods to quantify in biological matrices. Therefore, the objectives of the current study were: 1. to develop and validate a simple, rapid, and sensitive analytical method for simultaneous quantification of mesembrenone and mesembrine. 2. To apply this validated method to determine the plasma levels of these compounds in a pharmacokinetic study in mouse model (15 mg/kg). Ultra-High Performance Liquid Chromatography-Mass Spectrometry (UHPLC/QToF-MS) was used for the analysis and pharmacokinetic parameters were evaluated using Phoenix-WinNonlin Software (6.3). The lower limit of quantification for both the compounds was 5 ng/mL. The accuracy and precision were within ±15% (95 – 108%) for all QC samples (10, 250, and 1000 ng/mL). The area under curve (AUC) concentrations of mesembrenone and mesembrine were calculated to be 317 and 195 µg.h/L while the Cmax (maximum plasma concentrations) values were found to be 420 and 336 µg/L, respectively. This validated method was successfully used to evaluate the pharmacokinetics of mesembrine and mesembrenone in mouse plasma.