Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

Simultaneous determination of flavonols and terpene lactones in beagle dog plasma by ultra-performance liquid chromatography tandem mass spectrometry: 2. Application to pharmacokinetic studies on ginkgo leaf extract

Yang Lu, Pengyue Li, Huimin Liu, Shouying Du , Yanke Cheng, Huichao Wu, Jiannan Feng, Beibei Shao

School of Chinese Materia Medica, Beijing University of Chinese Medicine, Beijing 100102, China;

For correspondence:- Shouying Du Email: dushouying@263.net Tel:010-84738615

Received: 25 August 2014 Accepted: 6 April 2015 Published: 27 May 2015

Citation: Lu Y, Li P, Liu H, Du S, Cheng Y, Wu H, et al. Simultaneous determination of flavonols and terpene lactones in beagle dog plasma by ultra-performance liquid chromatography tandem mass spectrometry: 2. Application to pharmacokinetic studies on ginkgo leaf extract. Trop J Pharm Res 2015; 14(5):789-889 doi: 10.4314/tjpr.v14i5.19

© 2015 The authors.
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Abstract

Purpose: To evaluate the pharmacokinetics of the major compounds in Ginkgo leaf dosage formulations (namely, Yikangning tablets, Ginaton tablets, Aoshi dropping pills and Yinxinke dispersible tablets), commonly used in traditional Chinese medicine.

Methods: A randomized 4*4 crossover study with eight beagle dogs was carried out. Plasma samples were collected following oral administration of four different preparations and the effective ingredients, namely, kaempferol, quercetin, isorhamnetin, ginkgolides A, ginkgolides B, ginkgolides C and bilobalide were detected by a validated ultra-performance liquid chromatography-tandem mass spectrometry (UPLC-TMS). Then the pharmacokinetics of these target compounds, of different preparations were studied.

Results: The adjusted pharmacokinetic data showed that the area under the concentration-time curve from time-zero to the last measurable concentration (AUC_0-t) of kaempferol, quercetin, isorhamnetin, bilobalide, ginkgolides A, ginkgolides B, and ginkgolides C in plasma ranged from 124.37 ± 90.46 to 2261.87 ± 812.35, after administration of Yikangning; 142.28 ± 62.37 to 2529.46 ± 320.48 µg/L•h following administration of Ginaton; 158.52 ± 55.48 to 1987.40 ± 766.21 µg/L•h after Aoshi administration; 160.49 ± 104.66 to 2016.92 ± 1150.92 µg/L•h following Yinxinke administration. The results also indicate that the flavonoids (especially quercetin) in dispersible tablets and dropping pills hexhibited higher AUC than those in conventional tablets. There were no differences between Aoshi (dropping pills) and Yinxinke (dispersible tablets) in terms of the bioavailability of the flavonoids, but the dropping pill flavonoids showed lower t_max.

Conclusion: The results indicate that UPLC-TMS can used to simultaneously evaluate the plasma pharmacokinetics of Ginko compounds in beagle dogs

Keywords: Ginkgo biloba, Beagle dog plasma, Kaempferol, Quercetin, Isorhamnetin, Ginkgolides A, Ginkgolides B, Ginkgolides C, Bilobalide, Pharmacokinetics; Bioa