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

• Published in: BioMed research international Vol. 2018; no. 2018; pp. 1 - 8
• Main Authors: Wu, Bo, Wang, Xianqin, Cai, Yuan, Chen, Dingwen, You, Weiwei, Chen, Lian-Guo, Wen, Congcong
• Format: Journal Article
• Language: English
• Published: Cairo, Egypt Hindawi Publishing Corporation 01.01.2018; Hindawi; Hindawi Limited
• Subjects: Acetonitrile; Alternative medicine; Anesthetics, Dissociative - pharmacokinetics; Animals; Calibration; Carbamazepine; Chinese medicine; Chromatography; Chromatography, High Pressure Liquid; Chromatography, Liquid; Cytochrome; Diabetic neuropathy; Drug Interactions; Elution; Formic acid; Gene expression; Ketamine; Ketamine - pharmacokinetics; Laboratory animals; Linearity; Liquid chromatography; Mass spectrometry; Mass spectroscopy; Metabolism; Oxindoles - pharmacokinetics; Pharmaceuticals; Pharmacokinetics; Pharmacology; Quality control; Quantitative analysis; Random Allocation; Rats; Rats, Sprague-Dawley; Reproducibility of Results; Scientific imaging; Software; Spectroscopy; Tandem Mass Spectrometry; Uncaria; United States > US; China
• ISSN: 2314-6133; 2314-6141
• DOI: 10.1155/2018/6562309

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.