Interactions of pharmacokinetic profiles of Ginkgotoxin and Ginkgolic acids in rat plasma after oral administration

Ginkgolic acids (GAs) and Ginkgotoxin (4'-O-methylpyridoxine, MPN) are main toxic compounds in Ginkgo biloba seeds which are widely used in the treatment of coughing in China. To evaluate the pharmacokinetics of GAs, MPN and their metabolites in rat plasma, a highly sensitive method followed by ultra-high-pressure liquid chromatography coupled with linear ion trap-Orbitrap tandem mass spectrometry (UHPLC-LTQ-Orbitrap-MS) has been developed and validated. The proposed method is selective, precise and accurate enough of MPN and its metabolites (4-pyridoxic Acid, pyridoxal, and pyridoxine) for the pharmacokinetic study. After oral administration of MPN, the plasma concentrations of MPN and its metabolites were increased rapidly. Meanwhile, an investigation was carried out to compare the interactions of the pharmacokinetic profiles of MPN and GAs. Five GAs and main metabolites of GA (15:1) and GA (17:1) were also analyzed by using our previous method. After coadministration GAs with MPN, Tmax of MPN delayed and Cmax decreased. Meanwhile, Tmax of 4-pyridoxic Acid, pyridoxal, and pyridoxine were also showed a certain degree of delay. The concentrations of hydroxylation products of GA (15:1) and GA (17:1) increased at a slower rate and the area under the curves was significantly reduced. However, glucuronidation metabolites of GA (15:1) and GA (17:1) were increased faster than administered of GAs alone. The interactions of the pharmacokinetic profiles of GAs and MPN in rat plasma after oral administration were obviously observed.