Everted rat gut sac model was used to carry out the experiments about detoxification mechanism of Rhizoma Zingiberis on the diester-aconite alkaloids in Radix Aconiti. All the diester-aconite alkaloids were detected by Waters Ultra Performance Liquid Chromatography coupled with triple quadrupole Mass Spectrometry. Content of aconitine, mesaconitine and hypaconitine were calculated by standard curve method and other diester-aconite alkaloids were calculated by peak area. Results showed that the accumulative absorptive content of aconitine, mesaconitine, hypaconitine and the peak area of 10-OH-mesaconitine in unit area of the rat gut sac decreased when the extract of Rhizoma Zingiberis was added into K-R solution contained the exact of Radix Aconiti, and that increased when verapamil was added into K-R solution contained the exact of Radix Aconiti, which indicated the diester-aconite alkaloids might be the potential substrate of P-glycoprotein (P-gp). The accumulative content of digoxin in unit area of the rat gut sac decreased when the extract of Rhizoma Zingiberis was added into the intestinal nutritious solution contained digoxin, which indicated the extract of Rhizoma Zingiberis might be the revulsant of P-glycoprotein. On the basis of the above results, it could be concluded that the possible mechanism of the inhibition of the extract of Rhizoma Zingiberis on the absorption of the aconite alkaloids in the rat gut sacs was the extract of Rhizoma Zingiberis which served as the potential revulsant could inhibit the absorption of aconite alkaloids by inhibiting the activity of the intestinal P-gp.

Key words: everted rat gut sacs, aconite alkaloids, Rhizoma Zingiberis, ultra performance liquid chromatography-mass spectrometry, P-glycoprotein