Pharmacokinetics of R‐(−)ondansetron compared with that of S‐(−)ondansetron in rats using an LC–MS/MS method

: The pharmacokinetics of R-(-)ondansetron (R-ond) compared with that of S-(-)ondansetron (S-ond) was studied in rats. R-ond and S-ond were injected intravenously into rats at a dose of 2.0 mg/kg. The stability of ondansetron enantiomers in rat was determined by chiral HPLC, and the concentrations of R-ond and S-ond in plasma were determined by an LC/MS/MS method. The pharmacokinetic parameters were calculated and analyzed statistically using the t-test. The enantiomer inversions between R-ond and S-ond did not occur in rat. The pharmacokinetic parameters (t1/2 , AUC, MRT, CL) of R-ond and S-ond differed significantly. The concentration in plasma of the R/S-enantiomeric ratio reached a maximum value of 9.5 at 4.0 h post-dose. The pharmacokinetics of R-ond and S-ond are stereoselective in rat, which indicates substantial stereoselectivity in the disposition of ondansetron enantiomers in rat. R-ond has more potential than S-ond to be developed as a single enantiomer drug.