Study on the PK profiles of magnoflorine and its potential interaction in Cortex phellodendri decoction by LC-MS/MS

摘要

Magnoflorine, an aporphine alkaloid in Cortex phellodendri, is increasingly attracting research attention because of its antidiabetic effects. However, at present, little information on its pharmacokinetics (PK) in vivo is available. In this study, a sensitive, rapid, and selective method was developed to determine themagnoflorine content in rat plasma using liquid chromatography–tandem mass spectrometry. Following liquid–liquid extraction, the calibration curve showed good linearity within the concentration range of 2.93 to 1,500 ng ml~(?1). The intra- and inter-day precisions were all below 7.8 , and the accuracy ranged from 94.9 to 103.4 . The method was successfully applied in investigating the PK of magnoflorine in rats. The compound had low bioavailability, a high absorption rate, and a high elimination rate. However, area under the curve, T_(1/2), andMRTincreased approximately twofold when the same dosage of the compound was administered in a C. phellodendri decoction(20.8 g kg~(?1)). Moreover, T_(max) was prolonged from 0.3 to 3.33 h. Furthermore, a comparison of coadministration of the mixture group, magnoflorine (40 mg kg~(?1)) and berberine(696.4 mg kg~(?1)), with the C. phellodendri decoction group, revealed that no statistical difference (P >0.05) was found in the parameter AUC, and certain similar changes in the PK trend to the herbal medicine group were also observed. These results suggested that oral administration of the herbal medicine decreased the absorption and elimination rates of magnoflorine and increased its bioavailability. Berberine played a significant role in interacting with magnoflorine and in affecting the PK profiles of magnoflorine in the C. phellodendri decoction group.