Simultaneous Quantification of Multiple Active Components of the Combination of Ginkgo Ketoester Tablet and Donepezil in Four Biological Matrices from Dementia Mice: Application to Study the Distribution Patterns of the Two Drugs Based on “Brain-Gut” Axis
34 Pages Posted: 6 Oct 2021
Abstract
Ginkgo ketoester tablets (GT) and donepezil were a clinically used combination for the treatment of Alzheimer’s disease (AD). The aim of this study was undertaken to investigate anti-dementia effects of two drugs alone and in combination through monitoring the distribution patterns of active components in the important biological matrices based on the theory of “brain-gut” axis. A rapid and sensitive analytical method was developed for simultaneous quantification of 38 active compounds in the biological matrices at trace levels using ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-QTRAP Ò /MS 2 ). Under the optimized conditions, good chromatographic separation of 38 target compounds was achieved within 14 min, with acceptable linearity, limits of detections and quantifications, precision, stability, extraction recovery and matrix effects. The developed analytical method was used to quantify 38 active components in brain, plasma, intestinal and intestinal contents from AD mice treated with GT alone, donepezil alone, and the combination of two drugs. The result showed that that the combination group enhanced anti-dementia active compounds (including caffeic acid, isoginkgetin and sciadopitysin) and reduced the toxic compounds (such as GAs) entering into target tissues. These findings might be a reason for the increasing anti-dementia efficiency and reducing toxicity in the combination of GT and donepezil. In addition, the presented UHPLC-QTRAP Ò /MS 2 method might be used to monitor the target active compounds from different clinical biological fluids in the further study.
Note:
Funding Information: This work was supported by National Natural Science Foundation of China (No. 81803699), Natural Science Foundation of Jiangsu Province (No. BK20171068), Natural Science Foundation of Nanjing University of Chinese Medicine (No. NZY81803699), Jiangsu Collaborative Innovation Center of Chinese Medicinal Resources Industrialization (No. 012092002006-4), China Agriculture Research System of MOF and MARA (CARS-21), and a Project Funded by the Priority Academic Program Development of Jiangsu Higher Education Institutions (PAPD).
Declaration of Interests: There are no conflicts to declare.
Ethics Approval Statement: The experimental procedures were strictly conducted in accordance with ethical principle of animal, and the related protocol was reviewed and approved by the Animal Experimental Ethical Committee of Nanjing University of Chinese Medicine. The approval ethical file number was No. 201906A023.
Keywords: DementiaDonepezilGinkgo ketoester tablet"Brain-gut" axisMultiple active components
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