Pharmacokinetic Interaction Study of Ketamine and Rhynchophylline in Rat Plasma by Ultra-Performance Liquid Chromatography Tandem Mass Spectrometry

Abstract

Eighteen Sprague-Dawley rats were randomly divided into three groups: ketamine group, rhynchophylline group, and ketamine combined with rhynchophylline group (n = 6). The rats of two groups received a single intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline, respectively, and the third group received combined intraperitoneal administration of 30 mg/kg ketamine and 30 mg/kg rhynchophylline together. After blood sampling at different time points and processing, the concentrations of ketamine and rhynchophylline in rat plasma were determined by the established ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method. Chromatographic separation was achieved using a UPLC BEH C18 column (2.1 mm × 50 mm, 1.7 μm) with carbamazepine as an internal standard (IS). The initial mobile phase consisted of acetonitrile and water (containing 0.1% formic acid) with gradient elution. Multiple reaction monitoring (MRM) modes of m/z 238.1 → 179.1 for ketamine, m/z 385.3 → 159.8 for rhynchophylline, and m/z 237.3 → 194.3 for carbamazepine (IS) were utilized to conduct quantitative analysis. Calibration curve of ketamine and rhynchophylline in rat plasma demonstrated good linearity in the range of 1-1000 ng/mL (r > 0.995), and the lower limit of quantification (LLOQ) was 1 ng/mL. Moreover, the intra- and interday precision relative standard deviation (RSD) of ketamine and rhynchophylline were less than 11% and 14%, respectively. This sensitive, rapid, and selective UPLC-MS/MS method was successfully applied to pharmacokinetic interaction study of ketamine and rhynchophylline after intraperitoneal administration. The results showed that there may be a reciprocal inhibition between ketamine and rhynchophylline.

Pharmacokinetics and tissue distribution of N-3- methoxybenzyl-palmitamide in rat: A macamide derived from <i>Lepidium meyenii</i>

“…The elimination half-life of 7.44 ± 1.12 h showed that the elimination of MPM was slow in rats. The value of AUC (6485.75 ± 737.72 ng/mL•h) is not significant with a dose of 80 mg/kg compared to other reported drugs [15][16][17]. Unfortunately, there are missing data of absolute bioavailability, because direct intravenous drug delivery was unsuccessful in this experiment.…”

Pharmacokinetics of isocorynoxeine in rat plasma after intraperitoneal administration by UPLC–MS/MS

“…Liquid chromatography conditions separate isocorynoxeine from the endogenous interfering substances as much as possible from the analyte retention time [29][30][31][32][33][34]. In the investigation of chromatographic conditions, mobile phase systems such as methanol-water, acetonitrile-water, methanol-0.1% formic acid, and acetonitrile-0.1% formic acid were investigated.…”

Determination of diosmetin-7-o-β-d-glucoside in rat plasma by UPLC–MS/MS

“…Liquid chromatography conditions separate diosmetin-7-oβ-d-glucoside and IS as much as possible from the endogenous interfering substances [29][30][31][32]. In the investigation of chromatographic conditions, the mobile phase systems such as methanol-water, acetonitrile-water, methanol-0.1% formic acid, and acetonitrile-0.1% formic acid were investigated.…”