Effects of Montmorillonite Powers on the Absorption of Apatinib Mesylate in Rats
Objective:An UPLC-MS/MS method for determination of apatinib mesylate in rat plasma was established and applied to investigate the effects of montmorillonite powders on the absorption of apa-tinib mesylate in rats.Methods:Acetonitrile containing internal standard was used as protein precipitant to treat plasma samples,gradient elution was performed with 0.1％formic acid aqueous solution and acetoni-trile,apatinib mesylate was quantitatively analyzed in positive ion multi-reaction monitoring mode,and the established method was methodologically verified.Rats were randomly divided into three groups and given equal volumes of water(control group),a suspension containing montmorillonite powders 240 mg·kg-1(con-ventional dose group)or a suspension containing montmorillonite powder 2400 mg·kg-1(high dose group)by gavage.Then all rats were given apatinib mesylate 40 mg·kg-1 by gavage.Whole blood samples of each rat were collected through the jugular vein at different time points after administration,then plasma samples were pretreated and determined for the concentrations of apatinib mesylate.The plasma drug concentration-time curves were drawn and the pharmacokinetic parameters of apatinib mesylate were calculated by the WinNonlin(v 8.2)software.Results:The detection method had a good linear relationship in the range of 1-2000 ng·mL-1.The precision,accuracy,extraction recovery,matrix effect and stability met the related re-quirements.The peak concentrations of apatinib mesylate were(571±261),(650±215)and(961±390)ng·mL-1,respectively,and the areas under the curves were(3104±2463),(3624±1469)and(4578±2738)h·ng·mL-1,respectively.Conclusion:Montmorillonite powders probably affect the absorption of apatinib mesy-late in rats.It suggested that clinical attention should be paid to the interaction of montmorillonite powders and apatinib mesylate.
Montmorillonite powderApatinib mesylateAbsorptionDrug-drug interactionLiquid chro-matography tandem mass spectrometryRat
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