Liquid chromatographic/mass spectrometry assay of bromotetrandrine in rat plasma and its application to pharmacokinetic study.
A rapid and sensitive liquid chromatography-tandem mass spectrometric method (LC-MS/MS) for the determination of bromotetrandrine in rat plasma has been developed and applied to pharmacokinetic study in Sprague-Dawley (SD) rats after a single oral administration. Sample preparation involves a liquid-liquid extraction with n-hexane-dichlormethane (65:35, containing 1% 2-propanol isopropyl alcohol, v/v). Bromotetrandrine and brodimoprim (internal standard, IS) were well separated by LC with a Dikma C18 column using methanol-ammonium formate aqueous solution (20 mm) containing 0.5% formic acid (60:40, v/v) as mobile phase. Detection was performed on a triple quadrupole mass spectrometer in multiple reaction monitoring mode. The ionization was optimized using ESI+ and selectivity was achieved using MS/MS analysis, m/z 703.0 --> 461.0 and m/z 339.0 --> 281.0 for bromotetrandrine and IS, respectively. The present method exhibited good linearity over the concentration range of 20-5000 ng/mL for bromotetrandrine in rat plasma with a lower limit of quantification of 20 ng/mL. The intra- and inter-day precisions were 2.8-7.5% and 3.2-8.1%, and the intra- and inter-day accuracy ranged from -4.8 to 8.2% and -5.6 to 6.2%, respectively. The method was successfully applied to a pharmacokinetic study after a single oral administration to SD rats with bromotetrandrine of 50 mg/kg.
Song
Naining
N
School of Chemical Engineering and Technology, Tianjin University, Tianjin 300072, People's Republic of China. songnaining@163.com
Zhang
Shaoyu
S
Li
Quansheng
Q
Liu
Changxiao
C
D000818:Animals; D044182:Benzylisoquinolines / Q000097:blood* / Q000493:pharmacokinetics*; D002853:Chromatography, Liquid / Q000191:economics / Q000379:methods*; D005260:Female; D006586:Hexanes / Q000737:chemistry; D016014:Linear Models; D008297:Male; D013058:Mass Spectrometry / Q000191:economics / Q000379:methods*; D008752:Methylene Chloride / Q000737:chemistry; D051381:Rats; D017207:Rats, Sprague-Dawley; D012680:Sensitivity and Specificity; D013997:Time Factors
D044182:Benzylisoquinolines; D006586:Hexanes; C514835:bromotetrandrine; C026385:n-hexane; D008752:Methylene Chloride