Determination of bicuculline in rat plasma by liquid chromatography mass spectrometry and its application in a pharmacokinetic study

作者：Ma, Jianshe; Lin, Chongliang; Wen, Congcong; Xiang, Zheng; Yang, Xuezhi; Wang, Xianqin^*

来源：Journal of Chromatography B-Analytical Technologies in the Biomedical and Life Sciences, 2014, 953: 143-146.

DOI：10.1016/j.jchromb.2014.02.006

• Bicuculline
• LC-MS
• Pharmacokinetics
• Rat plasma

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 5-500 ng/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 (2.1 mm x 150 mm, 5 mu m) 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 15 mg/kg bicuculline in rats.

• 出版日期2014-3-15
• 单位温州医科大学