Simultaneous quantification of multiple active components of the ginkgo ketoester tablet when combined with donepezil in four biological matrices from an Alzheimer’s animal model: Evaluation of drug distribution patterns in vivo

Abstract

Ginkgo ketoester tablets (GT) and donepezil are clinically used in combination to treat Alzheimer’s disease (AD). This study aimed to investigate the anti-dementia effects of two drugs alone and in combination by monitoring the distribution patterns of their active components in different biological matrices. A practical analytical method was developed for simultaneously quantifying 38 active compounds in different matrices at trace levels using ultra-performance liquid chromatography coupled with triple-quadrupole linear ion-trap tandem mass spectrometry (UHPLC-MS²). Under optimized conditions, good chromatographic separation of the 38 target compounds was achieved within 14 min, with acceptable linearity, limits of detections and quantifications, precision, stability, and extraction recovery and matrix effects. The developed analytical method quantified the 38 active components in the brain, plasma, intestine, and intestinal contents of AD mice treated with GT alone, donepezil alone, and a combination of the two drugs. The result showed that the combination group had enhanced anti-dementia active compounds and reduced levels of toxic compounds entering the targeted tissues. These findings support the combined use of GT and donepezil for increasing anti-dementia treatment efficiency and reducing toxicity. The proposed UHPLC-MS² strategy could be used to monitor the levels of active compounds from different biological matrices in future studies.

Graphical Abstract

Keywords:

• Dementia
• donepezil
• ginkgo ketoester tablet
• simultaneous quantification
• distribution patterns
• brain-gut axis

Author contributions

All authors contributed to the study conception and design. GZ, XH, and WP conceived the initial experimental conception and design; XH and JZ performed material preparation, data collection and analysis; GZ, XH, and JZ wrote the draft of the manuscript; GZ and WP revised the manuscript critically for important intellectual content; GZ, YZ, and XS helped perform the analysis with constructive discussions. All authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

Data availability statement

The other data and materials used or analyzed during the current study are available from the corresponding author Gui-Sheng Zhou ([email protected]) on reasonable request.

Additional information

Funding

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 333 High-level Talents Training Project Funded by Jiangsu Province.