Simultaneous quantification of ondansetron and tariquidar in rat and human plasma using a high performance liquid chromatography-ultraviolet method

Yae Eun Chong, Manting Chiang, Kiran Deshpande, Simon Haroutounian, Leonid Kagan, Jong Bong Lee

Research output: Contribution to journalArticlepeer-review

5 Scopus citations

Abstract

Ondansetron, a widely used antiemetic agent, is a P-glycoprotein (P-gp) substrate and therefore expression of P-gp at the blood–brain barrier limits its distribution to the central nervous system (CNS), which was observed to be reversed by coadministration with P-gp inhibitors. Tariquidar is a potent and selective third-generation P-gp inhibitor, and coadministration with ondansetron has shown improved ondansetron distribution to the CNS. There is currently no reported bioanalytical method for simultaneously quantifying ondansetron with a third-generation P-gp inhibitor. Therefore, we aimed to develop and validate a method for ondansetron and tariquidar in rat and human plasma samples. A full validation was performed for both ondansetron and tariquidar, and sample stability was tested under various storage conditions. To demonstrate its utility, the method was applied to a preclinical pharmacokinetic study following coadministration of ondansetron and tariquidar in rats. The presented method will be valuable in pharmacokinetic studies of ondansetron and tariquidar in which simultaneous determination may be required. In addition, this is the first report of a bioanalytical method validated for quantification of tariquidar in plasma samples.

Original languageEnglish
Article numbere4653
JournalBiomedical Chromatography
Volume33
Issue number11
DOIs
StatePublished - Nov 1 2019

Keywords

  • P-gp inhibitor
  • bioanalytical method
  • biological matrices
  • central nervous system
  • preclinical pharmacokinetics

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