Pharmacokinetic studies of ginkgolide K in rat plasma and tissues after intravenous administration using ultra-high performance liquid chromatography-tandem mass spectrometry.
Ginkgolide K (GK), a derivative compound of ginkgolide B, has been recently isolated from the leaves of Ginkgo biloba. It is a powerful natural platelet activate factor (PAF) antagonist, and also has obvious protect effects for cerebral ischemia. However, no reports have been described for the pharmacokinetic study of GK. In this study, a simple, sensitive and reliable ultra-high performance liquid chromatography-tandem mass spectrometry (UHPLC-MS/MS) method has been developed for the determination of GK in rat plasma and tissues. Biological samples were pretreated by an efficient liquid-liquid extraction with ethyl acetate. The chromatographic separation was achieved on an Agilent ZORBAX SB-Aq column (4.6 mm × 50 mm, 1.8 μm) with a mobile phase of 0.5% aqueous formic acid (A)-menthol (B). Quantitation was carried out on a triple quadruple mass spectrometry using positive electrospray ionization in multiple reaction monitoring mode. Diazepam was used as internal standard (IS). The ion transitions monitored were set at m/z 407.10 → 389.20 and m/z 285.08 → 193.10 for GK and IS, respectively. The developed method was fully validated and successfully applied to the pharmacokinetics and tissue distribution study of GK after intravenous administration. The current results have indicated that pharmacokinetic parameters of GK vary in a dose-dependent manner with rapid elimination in 4h. The major distribution tissues of GK in rats were liver and kidney. This study would provide critical information to promote the future study of GK.
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Zhi-Ying
ZY
Fan
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Xin-Guang
XG
Liu
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Ru-Zhou
RZ
Guo
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Xin
X
Dong
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China.
Wen
W
Gao
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: liping2004@126.com.
Ping
P
Li
State Key Laboratory of Natural Medicines, China Pharmaceutical University, Nanjing 210009, China. Electronic address: yanghuacpu@126.com.
Hua
H
Yang
D061605:Administration, Intravenous; D000818:Animals; D002851:Chromatography, High Pressure Liquid / Q000379:methods*; D004355:Drug Stability; D046934:Ginkgolides / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D007783:Lactones / Q000008:administration & dosage / Q000032:analysis* / Q000097:blood / Q000493:pharmacokinetics*; D016014:Linear Models; D051381:Rats; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012680:Sensitivity and Specificity; D053719:Tandem Mass Spectrometry / Q000379:methods*; D014018:Tissue Distribution
D046934:Ginkgolides; D007783:Lactones; C481151:ginkgolide K
Ginkgo; Ginkgolide K; Pharmacokinetics; Tissue distribution; UHPLC-MS/MS