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Simultaneous determination of Rivaroxaban and TAK-438 in rat plasma by LC-MS/MS: application to pharmacokinetic
Libin Wang1, Shouchang Gai2, Xiaorui Zhang3
1Graduate School, Shaanxi University of Chinese Medicine, Xi'an 712046, PR China.
Abstract:
Aim: A sensitive and reliable LC-MS/MS method has been established and validated to the quantitation of rivaroxaban (RIV) and TAK-438 in rat plasma using carbamazepine as internal standard. Results: The procedure of method validation was conducted according to the guidelines of EMA and US FDA. At the same time, the method was applied to pharmacokinetic interactions study between RIV and TAK-438 for the first time. When RIV and TAK-438 co-administration to rats, main pharmacokinetic parameters of TAK-438 like AUC(0-t), AUC(0-∞) and Cmax had statistically significant increase. The main pharmacokinetic parameters of RIV have no statistically significant difference (p > 0.05) when co-administered except for t1/2 (p < 0.01). Conclusion: The results indicated that drug-drug interactions occurred between RIV and TAK-438 when co-administered to rats.
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