期刊
JOURNAL OF CHROMATOGRAPHY A
卷 1073, 期 1-2, 页码 317-322出版社
ELSEVIER SCIENCE BV
DOI: 10.1016/j.chroma.2004.10.048
关键词
genistein; hepatobiliary excretion; microdialysis; pharmacokinetics
Genistein, the major isoflavone in soybeans, has been shown to have a wide range of effects. We used an HPLC-UV combined with microdialysis method to detect unbound genistein in rat blood, brain and bile. Genistein dialysates were eluted with a mobile phase containing acetonitrile-water (40:60, v/v, pH 3.5 adjusted by 0.1% acetic acid). Samples were separated using a phenyl (5 μ m) column maintained at ambient temperature. The UV detector wavelength was set at 259 nm. The flow rate was 1.0 ml/min. The limit of quantitation for genistein was 50 ng/ml. The in vitro recoveries of genistein were 31 ± 1, 13 ± 1 and 59 ± 4% in microdialysis probes of blood, brain and bile, respectively (n = 4). Inter- and intra-assay accuracy and precision of the analysis were less than 10% in the concentration ranges of 0.05-5.0 μ g/ml. A small ratio of genistein penetrates the blood-brain barrier (BBB) and goes through hepatobiliary excretion after genistein administration (10 or 30 mg/kg, i.v.). The brain-to-blood (AUC(brain)/AUC(blood)) and bile-to-blood (AUC(bile)/AUC(blood)) distribution ratios were 0.04 ± 0.01 and 1.85 ± 0.42, respectively for the dosage of genistein 30 mg/kg. After co-administration of cyclosporine, a P-glycoprotein (P-gp) inhibitor, the distribution ratios of genistein in brain and bile were not significantly altered. These results suggest that the BBB penetration and hepatobiliary excretion of genistein may not regulated by P-gp. © 2004 Elsevier B.V. All rights reserved.
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