Abstract
As a potent drug used to improve the neurodegenerative conditions, there is few information about the brain tissue distribution of tranilast by now. In this study, a novel sensitive LC–MS/MS method has been developed and validated to determine tranilast in rat brain tissue samples. The calibration curve showed good linearity ranged from 2.140 to 428.0ng·mL−1. The method was fully validated and successfully applied in the brain tissue distribution study of tranilast in rats, which had never been reported in detail by now. Furthermore, a rapid LC–MS/MS method with a short run time of 3min was developed and validated for the determination of tranilast in rat plasma and the application to a pharmacokinetic study of tranilast in rats. After oral dosage of 10.5mg·kg−1 tranilast, the maximum plasma concentration (Cmax1) of tranilast was (18.59±5.40) μg·mL−1 at (0.667±0.408) h while the area under the curve (AUC0-24) was (54.87±14.13) μg·h·mL−1 with the elimination half-life of (2.93±0.41) h. The ratio calculated by dividing the concentration of tranilast in brain with the concentration of tranilast in the plasma, was (0.6042%±0.0572%), (0.7484%±0.0883%), (0.5914%±0.0416%) and (0.3830%±0.1632%) at 0.167, 0.5, 2 and 8h, respectively. The results showed that tranilast with fast absorption could penetrate the rat brain blood barrier after oral gavage. The obtained data also showed that tranilast could be quickly distributed and eliminated in brain tissue.
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