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.
Highlights
Ketamine is clinically used for surgical anesthesia [1, 2]
Y1 represents the ratios of peak intensity of ketamine to the internal standard, and X1 represents the concentration of ketamine in plasma; Y2 represents the ratios of peak intensity of rhynchophylline to the internal standard, and X2 represents the concentration of rhynchophylline in plasma
The mean recovery was higher than 66.2% and the matrix effect was between 98.8% and 102.7%. These results demonstrated that the precision, accuracy, recovery, and matrix effect of the established UPLC-MS/MS method were all conformed to the pharmacokinetic requirements of ketamine and rhynchophylline
Summary
Ketamine is clinically used for surgical anesthesia [1, 2]. Commonly known as “K powder”, ketamine was epidemically abused in the United States in the early 70s of last century [3, 4]. Ketamine was often abused in entertainment venues, making it one of the relatively popular new drugs currently [7, 8]. Traditional Chinese medicines such as Gastrodia Elata and Uncaria which can suppress hyperactive liver for calming endogenous wind, together with drugs which can warm kidney and activate yang and disperse stagnated liver qi for relieving qi stagnation, are used in clinical treatment with a good therapeutic effect [9, 10]. As a common traditional Chinese medicine in modern detoxification compound, Uncaria is frequently used as the main drug in detoxification preparations, such as Kangfuxin capsule, composite Dongyuan Gao, Shutongan capsule, and other preparations. Clinical studies have confirmed that these traditional Chinese medicine compounds are effective in controlling the withdrawal symptoms, relieving mental dependence, and BioMed Research International
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