LC-MS/MS method for simultaneous determination of rivaroxaban and metformin in rat plasma: application to pharmacokinetic interaction study.

Aim: A reliable, sensitive and simple LC-MS/MS method has been established and validated for the quantitation of rivaroxaban (RIV) and metformin (MET) in rat plasma. Results: The procedure of method validation was conducted according to the guiding principles of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and MET for the first time. When RIV and MET coadministered to rats, pharmacokinetic parameters of MET like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increased. tmax of RIV was prolonged without affecting t1/2 obviously and Cmax was inhibited significantly (p < 0.05) by comparison to the single group. Conclusion: The results indicated that drug-drug interactions occurred when the coadministration of RIV and MET.