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.
Objective
In this study, we aimed to investigate the potential interaction of apatinib and buspirone and underlying mechanism.
Methods
UPLC‐MS/MS assay was applied to determine the concentrations of buspirone and its main metabolites (1‐PP and 6‐OH buspirone) after incubated with liver microsomes. Moreover, the connection of in vitro and in vivo was further determined. Sprague Dawley rats were randomly divided into two groups: group A (20 mg/kg buspirone) and group B (buspirone vs 40 mg/kg apatinib). Tail vein blood was collected and subjected to the UPLC‐MS/MS detection.
Key findings
Apatinib inhibited the generations of 1‐PP and 6‐OH buspirone dose‐dependently with IC50 of 1.76 and 2.23 μm in RLMs, and 1.51 and 1.48 μm in HLMs, respectively. There was a mixed mechanism underlying such an inhibition effect. In rat, AUC(0–t), AUC(0–∞), Tmax and Cmax of buspirone and 6‐OH buspirone increased significantly while co‐administering with apatinib, but Vz/F and CLz/F decreased obviously while comparing group A with group B .
Conclusions
Apatinib suppresses the CYP450 based metabolism of buspirone in a mixed mechanism and boosted the blood exposure of prototype drug and 6‐OH buspirone dramatically. Therefore, extra caution should be taken when combining apatinib with buspirone in clinic.
Background:
Ginsenoside Rg1 (Rg1) is the main active compound of ginseng herbs.
Objective:
The aim of this study is to develop a rapid, selective and sensitive ultra-high performance
liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method to determine the levels of
Rg1 in rat plasma and investigate the pharmacokinetics and bioavailability of Rg1 in rats.
Methods:
Chromatographic separation was achieved on an UHPLC-MS/MS system with an UPLC
BEH C18 column using an elution gradient of a mixture of acetonitrile and water (with 0.1% formic
acid). The analytes were quantitatively determined by negative-mode electrospray tandem MS.
Results:
The linearity of the calibration curve was from 2 to 1,000 ng/mL (r ≥ 0.9956), and the lower
limit of quantification was 2 ng/mL. The inter-day and intra-day precision were both lower than 12.0%,
and the accuracy ranged from 90.6 to 109.7%. The recovery of the targets was higher than 87.0%, and
the matrix effect at three different analyte concentrations were from 89.0 to 97.2%. The bioavailability
of Rg1 was only 6.1% due to a poor oral absorption.
Conclusion:
This new quantitative method was found to be sensitive, rapid and selective, and was successfully
used to study the pharmacokinetics of Rg1 after intravenous and oral administration in rats.
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