Pharmacokinetics of bilobalide, ginkgolide A and B after administration of three different Ginkgo biloba L. preparations in humans.

A sensitive LC-ESI-MS method with a solid-phase extraction was established for the determination of bilobalide, ginkgolide A and ginkgolide B in human plasma; bioavailability and pharmacokinetics of three different Ginkgo biloba L. preparations have been investigated. The preparations used in the present single-dose pharmacokinetic study were different formulations of Ginkgo biloba L. extracts (Geriaforce tincture, new Ginkgo fresh plant extract tablets and EGb 761) with various excipients. The analysis of Ginkgo terpene lactones was performed by LC-MS on a Zorbax SB-C18 column. The mobile phase consisted of water + 0.1% acetic acid and methanol 68/32 (v/v) to 49/51 (v/v) at a flow rate of 200 microL/min. Bilobalide, ginkgolide A and ginkgolide B were monitored using the selected-ion monitoring (SIM) mode at m/z of 325, 453 and 423, respectively.The amounts of the active compounds (terpene lactones) in the administered products were in the low-mg range per dose. The assay method was successfully applied to the study of the pharmacokinetics and bioavailability of bilobalide, ginkgolide A and ginkgolide B in humans. The resulting maximum concentrations (median) of bilobalide, ginkgolide A and ginkgolide B in plasma after administration of the maximum daily dose of the different Ginkgo products were 3.53, 3.62, and 1.38 ng/mL respectively after administration of Geriaforce tincture; 11.68, 7.36, and 4.18 ng/mL, respectively after taking Ginkgo fresh plant extract tablets; and 26.85, 16.44, 9.99 ng/mL, respectively after administration of EGb 761 tablets. These data are relevant to demonstrate relative bioavailabilities of different Ginkgo biloba L. preparations (Geriaforce tincture, new Ginkgo fresh plant extract tablets and EGb 761).

Woelkart K ，Feizlmayr E ，Dittrich P ，Beubler E ，Pinl F ，Suter A ，Bauer R ... -  《-》

[Pharmacokinetic properties of Bilobalide and Ginkgolides A and B in healthy subjects after intravenous and oral administration of Ginkgo biloba extract (EGb 761)].

Fourtillan JB ，Brisson AM ，Girault J ，Ingrand I ，Decourt JP ，Drieu K ，Jouenne P ，Biber A ... -  《THERAPIE》

Bioavailability of ginkgolides and bilobalide from extracts of ginkgo biloba using GC/MS.

Biber A ，Koch E 《PLANTA MEDICA》

Determination of Ginkgolides A, B, C, J and Bilobalide in Plasma by LC-ESI (-)/MS/MS (QQQ) and its Application to the Pharmacokinetic Study of Ginkgo Biloba Extract in Rats.

A simple, rapid, and specific high-performance liquid chromatograph coupled with a tandem mass spectrometry method has been developed and validated for the quantification of ginkgolides in rat plasma, and the main pharmacokinetic parameters of ginkgolides after oral administration of Ginkgo biloba extract (GBE) was acquired. Methods: Plasma samples were pretreated with ethyl acetate extraction. Sulfamethoxazole was used as the internal standard (IS). Chromatographic separation was achieved on an Eclipse XDB-C18 column (2.1 mm×150 mm, 5 μm) with a mobile phase consisting of methanol/0.1% formic acid water (gradient elution: 0~25 min (77:23)→(60:40), V/V) at a flow rate of 0.3 mL·min-1. The detection was performed on a triple quadruple tandem mass spectrometer using an electrospray ionization (ESI) source for 25 min. The detection was operated by multiple reaction monitoring(MRM) under negative ionization mode of the transitions of m/z 325→163 for BB, 469→423 for GJ, 439→125 for GC, 453→351 for GA, 423→367 for GB and of m/z 252→156 for sulfamethoxazole (IS) respectively. Results: The pharmacokinetic properties of BB, GJ, GA, GB and GC were in line with the open 2-compartment model after oral administration of GBE in rats; The pharmacokinetic parameters of various lactones were calculated, and drugs-time curve and the curve fitting diagram of 5 ginkgolides were drew; The absorption and distribution rate of BB, GJ, GA, GB and GC were fast in rats in vivo, and half-life of absorption was less than 3 h. Conclusion: The developed LC-ESI (-)/MS/MS (QQQ) method was successfully applied to assess the pharmacokinetic parameters and oral bioavailability of ginkgolides in rats after administration of GBE, which can provide basis for further clinical efficacy studies.

Yan-Yan Z ，Li-Li G ，Guo-Ming S ，Rong R ，Jing-Zhen T ... -  《-》

Simultaneous determination of ginkgolides A, B, C and bilobalide in plasma by LC-MS/MS and its application to the pharmacokinetic study of Ginkgo biloba extract in rats.

Xie J ，Ding C ，Ge Q ，Zhou Z ，Zhi X ... -  《JOURNAL OF CHROMATOGRAPHY B-ANALYTICAL TECHNOLOGIES IN THE BIOMEDICAL AND LIFE SCIENCES》