Abstract: Objective To develop and validate a sensitive and reliable liquid chromatography-tandem mass/mass spectrometry (LC-MS/MS) method for the determination of ondansetron in human plasma and evaluate the bioequivalence of oral ondansetron dissolved film. Methods The method involved the addition of internal standard solution to plasma samples, followed by liquid-liquid extraction with 0.5 mL of ethyl acetate. After vortexing and centrifugation, supernatant was transferred and evaporated to dryness in a slight stream of nitrogen. The residue was dissolved in 100 µL of mobile phase, and 10 µl of it was used for LC-MS/MS analysis. The separations were performed on a ZORBAX SB-C18 2.1 mm×50 mm 3.5 µm, with 0.1% formic acid and methyl alcohol as mobile phase, and the detection was performed on tandem mass/mass spectrometry by the multiple-reaction monitoring via an electrospray ionization source. Results The standard curve was linear over the concentration range from 0.2 to 80 ng·mL^-1. The lower limit of quantification was 0.2 ng·mL^-1 using 100 μL of human plasma sample. The intra- and inter-assay precision and accuracy were found to be less than 5.94% and 6.22%, respectively. Conclusion This developed analytical method was successfully applied to the pharmacokinetics and bioequivalence study of ondansetron in healthy Chinese volunteers.

Key words: ondansetron, bioequivalence, pharmacokinetics, LC-MS-MS, bioavailability