Simultaneous quantification of ondansetron and tariquidar in rat and human plasma using a high performance liquid chromatography-ultraviolet method.
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.
['Chong|Yae Eun|YE|', 'Chiang|Manting|M|', 'Deshpande|Kiran|K|', 'Haroutounian|Simon|S|', 'Kagan|Leonid|L|', 'Lee|Jong Bong|JB|https://orcid.org/0000-0002-8404-0581']
D000818:Animals D002851:Chromatography, High Pressure Liquid D006801:Humans D057230:Limit of Detection D016014:Linear Models D008297:Male D017294:Ondansetron D011804:Quinolines D051381:Rats D017207:Rats, Sprague-Dawley D015203:Reproducibility of Results D013056:Spectrophotometry, Ultraviolet
central nervous system P-gp inhibitor bioanalytical method preclinical pharmacokinetics biological matrices