title: Determination of bicuculline in rat plasma by liquid chromatography mass spectrometry and its application in a pharmacokinetic study.
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.
authors.affiliation: Laboratory Animal Centre of Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Jianshe
authors.initials: J
authors.lastname: Ma
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Chongliang
authors.initials: C
authors.lastname: Lin
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Congcong
authors.initials: C
authors.lastname: Wen
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University, Wenzhou 325035, China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Xiang
authors.affiliation: The First Affiliated Hospital of Wenzhou Medical University, Wenzhou 325000, China.
authors.forename: Xuezhi
authors.initials: X
authors.lastname: Yang
authors.affiliation: Analytical and Testing Center of Wenzhou Medical University, Wenzhou 325035, China. Electronic address: lankywang@163.com.
authors.forename: Xianqin
authors.initials: X
authors.lastname: Wang
mesh_terms: D000818:Animals; D001640:Bicuculline / Q000097:blood* / Q000737:chemistry / Q000493:pharmacokinetics; D002853:Chromatography, Liquid / Q000379:methods*; D004355:Drug Stability; D057230:Limit of Detection; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000379:methods*; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results
chemical_list: D001640:Bicuculline
keywords: Bicuculline; LC–MS; Pharmacokinetics; Rat plasma