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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

Shanghai Institute of Pharmaceutical Industry, National Pharmaceutical Engineering and Research Center, 1111 Halei Road, Zhangjiang Hi-Tech Park, Shanghai 201203, PR China.

A new liquid chromatography tandem mass spectrometry (LC-MS/MS) method for the simultaneous determination of ginkgolides (includes ginkgolide C for the first time) and bilobalide in plasma is presented. Ketoprofen was used as an internal standard, and sample pre-treatment consisted of a liquid-liquid extraction. Chromatographic separation was achieved on a 5mum Shiseido C8 column (150mmx2.0mm i.d., particle size 5mum) with a mobile phase consisting of methanol/6mM ammonium acetate (60/40, v/v) at a flow rate of 0.3ml/min. A tandem mass spectrometric detection was conducted using multiple reaction monitoring (MRM) under negative ionization mode with an atmospheric pressure chemical ionization (APCI) interface. The method was validated in terms of intra- and inter-day precision (<12.7%), accuracy (within +/-7.0%), linearity, specificity and stability. In addition, matrix effects of ginkgolides and bilobalide in plasma were evaluated in different reconstitution solvents. Smaller matrix effects were observed for reconstitution solvents containing less organic solvent. The method has been successfully applied to a pharmacokinetic study of Ginkgo biloba extract in rats after intravenous administration. This is the first report of pharmacokinetic data for ginkgolide C.

Published 17 March 2008 in J Chromatogr B Analyt Technol Biomed Life Sci, 864(1): 87-94.
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