Pharmacokinetics and tissue distribution study of ginkgolide L in rats by ultra-high performance liquid chromatography coupled with tandem mass spectrometry

An ultra-high performance liquid chromatography coupled with tandem mass spectrometry (UHPLC-MS/MS) approach was developed and validated for the determination of ginkgolide L (GL) in rat plasma and tissues using diazepam as internal standard (IS). Detection was performed on a triple quadrupole MS system using multiple reaction monitoring (MRM) mode in positive mode. Sample preparation was carried out through a liquid-liquid extraction with ethyl acetate. The chromatographic separation was achieved by using an Agilent ZORBAX SB-Aq column with a mobile phase of 0.5% aqueous formic acid (A) and methanol (B). The monitored transitions were set at m/z 391.14 -> 271.10 for GL and m/z 285.08 -> 193.10 for IS, respectively. The validated method was successfully applied to the pharmacokinetic and tissue distribution study of GL in rats after intravenous administration. Good linearity was found between 2.5-2000 ng/mL (r>0.996) for plasma samples, and calibration curves were also linear for other tissue samples over a wide range. The results indicated that GL has linear pharmacokinetic properties after intravenous administration at three doses. GL could distribute to tissues quickly and the major distribution tissue of GL in rats was liver. This was the first report of pharmacokinetic and tissue distribution data for GL. (C) 2015 Elsevier B.V. All rights reserved.