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  • Title: Determination of bicuculline in rat plasma by liquid chromatography mass spectrometry and its application in a pharmacokinetic study.
    Author: Ma J, Lin C, Wen C, Xiang Z, Yang X, Wang X.
    Journal: J Chromatogr B Analyt Technol Biomed Life Sci; 2014 Mar 15; 953-954():143-6. PubMed ID: 24607696.
    Abstract:
    Bicuculline, a phthalide isoquinoline alkaloid is of current interest as an antagonist of gamma-aminobutyric acid (GABA). A simple and sensitive liquid chromatography mass spectrometry method for determination of bicuculline in rat plasma was developed over the range of 5-500ng/mL. After addition of midazolam as internal standard, protein precipitation with acetonitrile-methanol (9:1, v/v) was used as sample preparation. Chromatographic separation was achieved on a Zorbax SB-C18 (2.1mm×150mm, 5μm) column with acetonitrile -0.1% formic acid in water as mobile phase with gradient elution. Electrospray ionization (ESI) source was applied and operated in positive ion mode; selective ion monitoring (SIM) mode was used for quantification using target fragment ions m/z 368 for bicuculline and m/z 326 for the IS. Linear calibration was obtained with correlation coefficients r>0.99. The CV of the precision measurements was less than 13%. The accuracy of the method ranged from 93.6% to 100.5%. Mean recoveries of bicuculline in plasma were in the range of 80.5-91.8%. The method was successfully applied to the pharmacokinetic study after gavage administration of 15mg/kg bicuculline in rats.
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