1. Poly-pharmacokinetic strategy-delineated metabolic fate of bioactive compounds in a traditional Chinese medicine formula, Yuanhu Zhitong tablets, using parallel reaction monitoring mode.
- Author
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Ping W, Tinglan Z, Guohua Y, Mengjie L, Jin S, Jiaqi Z, Ke L, Yan F, Haiyu X, and Hongjun Y
- Subjects
- Administration, Oral, Animals, Area Under Curve, Berberine Alkaloids blood, Chromatography, High Pressure Liquid, Drug Stability, Drugs, Chinese Herbal administration & dosage, Limit of Detection, Rats, Sprague-Dawley, Tablets administration & dosage, Tablets chemistry, Chromatography, Liquid methods, Drugs, Chinese Herbal pharmacokinetics, Mass Spectrometry methods, Tablets pharmacokinetics
- Abstract
Objective: To evaluate the pharmacokinetics of eight constituents in Yuanhu Zhitong tablets, which may provide a method for the poly-pharmacokinetic study of traditional Chinese medicine., Methods: A robust platform using Thermo Scientific™ Dionex™ UltiMate™ 3000 rapid separation LC, integrated with Thermo Scientific™ Q Exactive™ MS, was developed and validated to acquire, in a high-resolution full-scan mode, a global profile of all ionized components in rat plasma after oral administration of a suspension of Yuanhu Zhitong tablets., Results: This robust UPLC-HRMS method was successfully applied for pharmacokinetic evaluation after oral administration of Yuanhu Zhitong tablets. The MS response showed a good linear relationship, with a coefficient of determination (r
2 ) of >0.99. The levels of detection were in the range of 0.088-0.414 ng·ml-g for the different constituents. The recoveries ranged from 92.23% to 104.47%, and the matrix effect ranged from 85.24% to 101.02%. The intra- and inter-day accuracy was in the range of 0.00-12.54%, while the intra- and inter-day precision ranged from 0.44% to 7.63%. Short-term stability, long-term stability, freeze-thaw stability, and post-preparative stability ranged from -recision rangedThe time to reach peak plasma concentration (tmax ) values for the analytes was less than 10 h, except that for tetrahydropalmatine, which was quickly absorbed into the bloodstream. The large area under the concentration-time curve (AUC) values (≥105 ng·h·l-g ) for the eight compounds indicated good absorption and utility in rat plasma. The mean residence time was more than 6 h, indicating slow elimination., Conclusion: UPLC-HRMS was shown to be a very promising and powerful tool for the kinetic screening and characterization of compounds in medicinal herbs and traditional Chinese medicine formulas. Pharmacokinetic profiling of multiple compounds enables the clarification of metabolic processes and fates of the selected medicinal herbs or traditional Chinese medicine formula. This allows us to better understand the actions and associated therapeutic mechanisms of the traditional Chinese medicine., (Copyright © 2018 Elsevier GmbH. All rights reserved.)- Published
- 2019
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