High Resolution Determination of Ondansetron in Human Plasma by HPLC and Pharmacokinetics of Orally Disintegrating Tablets

Aim To develop a high resolution HPLC method for the determination of ondansetron in human plasma and to study the pharmacokinetics of ondansetron in orally disintegrating tablets.Methods HPLC determination involved liquid-liquid extraction, separation on a CN column and ultraviolet detection at 310 nm with granisetron as an internal standard. Pharmacokinetics and bioequivalence of ondansetron in orally disintegrating tablets by direct compression and conventional 8 mg tablets were evaluated and compared in 20 healthy human male volunteers after a single oral dose in a randomized cross-over study. Results The limit of quantification was 0.25 ng·mL~ -1. The recovery was about 85% or over for ondansetron and about 90% for internal standard. Linearity was good within the concentration range of 0.5-50 ng·mL~ -1 with r~2 ranging from 0.997 1 to 0.999 9. Intra- and inter-assay coefficients of variation ranged from 1.78% to 2.38% and 3.88%-5.19%, respectively. Accuracies for spiked concentrations of 2.0, 10.0, and 30.0 ng·mL~ -1 were 104.7%±4.4%, 102.2%±1.1%, and 99.51%±2.34%, respectively. Pharmacokinetic parameters of AUC 0-t, AUC 0-∞, C max, T max, and T 1/2 were 230.2±78.0 ng·h·mL~ -1, 265.2±101.5 ng·h·mL~ -1, 35.67±8.94 ng·mL~ -1, 1.51±0.79 h, and 5.00±1.41 h for orally disintegrating tablets, respectively. The analysis of variance did not show any significant difference between orally disintegrating tablets and conventional tablets, and 90% confidence intervals fell within the acceptable range for bioequivalence. Conclusion High resolution HPLC method has been set up and applied in pharmacokinetic evaluation of ondansetron in orally disintegrating tablets.