Sensitive and selective liquid chromatography-electrospray ionization mass spectrometry analysis of ginkgolide B in dog plasma.
As an important active constituent of Ginkgo biloba extract, ginkoglide B is a highly selective and competitive PAF receptor antagonist which has been widely used in clinical applications. A novel high-performance liquid chromatography-electrospray ionization mass spectromentry (LC-ESI-MS) method was developed for the determination of ginkgolide B in dog plasma. After liquid/liquid extraction with ether and high-performance liquid chromatography (HPLC) gradient separation with 0.01% of ammonia water (v/v)-methanol as the mobile phase, the deprotonized anions [M-H](-1) at m/z 423 of ginkoglide B, and [M-H](-1) at m/z 492 of internal standard (IS) glibenclamide were analyzed by LC-ESI-MS in selected ion monitoring (SIM) mode. Chromatographic separation was achieved in less than 9 min and calibration curve was linear over a concentration range of 0.1-20 ng/ml. The described assay method was successfully applied to the pre-clinical pharmacokinetic study of ginkoglide B. After intragastric administration of ginkgolide B to beagle dogs, C(max) and T(max) of ginkgolide B were 43.8 +/- 6.24 ng/ml and 0.5 h, respectively, and the elimination half-life (t(1/2)) was 2.85 +/- 0.54 h.
Hua
Lv
L
Key Laboratory of Drug Metabolism and Pharmacokinetics, China Pharmaceutical University, Nanjing 210009, China.
Guangji
Wang
W
Hao
Li
L
Minwen
Huang
H
Haitang
Xie
X
Chenrong
Huang
H
Jianguo
Sun
S
Tian
Lv
L
D000818:Animals; D002138:Calibration; D002623:Chemistry Techniques, Analytical / Q000379:methods; D002626:Chemistry, Pharmaceutical / Q000379:methods*; D002845:Chromatography / Q000379:methods; D002851:Chromatography, High Pressure Liquid; D002853:Chromatography, Liquid / Q000379:methods*; D004224:Diterpenes / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics; D004285:Dogs; D005343:Fibrinolytic Agents / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics; D005615:Freezing; D046934:Ginkgolides; D007783:Lactones / Q000032:analysis / Q000097:blood* / Q000493:pharmacokinetics; D008956:Models, Chemical; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D021241:Spectrometry, Mass, Electrospray Ionization / Q000379:methods*; D013696:Temperature; D013997:Time Factors
D004224:Diterpenes; D005343:Fibrinolytic Agents; D046934:Ginkgolides; D007783:Lactones; C045856:ginkgolide B