Determination of ornidazole in plasma by HPLC and study on its pharmacokinetics and bioequivalence of domestic and imported tablets in 18 healthy volunteers

OBJECTIVE To establish a reversed HPLC method for the determination of ornidazole in human plasma, and study the pharmacokinetics and bioequivalence of domestic and imported tablets in healthy volunteers.METHOD The drug was extracted from plasma with methanol and isopropanol (50∶50), and then analyzed by HPLC with a C 18 5μm 250×4.6mm column and UV detector set at 316nm. The mixture of methanol and 0.4% glacial acetic acid (50∶50) was used as the mobile phase. The flow rate is 0.8mL·min -1 . 1.5g single oral dose of domestic and imported ornidazole tablets were given to 18 healthy volunteers in an open randomized crossover study. The pharmacokinetic parameters as well as relative bioavailability were measured.RESULTS The calibration curve was linear within the range of 2.0～20.0μg·mL -1 and the measurable lowest limit was 0.2μg·mL -1 . The average recovery of ornidazole at the concentrations of 2.0, 10.0, 20.0μg·mL -1 was 100.36%, 98.21% and 97.42%, respectively. The RSD of the within-day and between-day were less than 7% and 6%, respectively. The results showed that the concentration-time curves of the two preparations were fitted to a two -compartment model with a lag time. The major pharmacokinetic parameters of domestic and imported ornidazole tablets were shown respectively as following: t 1/2(β) were (16.29±2.20)h and (15.85±2.26)h ;T max were (1.67±0.49)h and (1.75±0.48)h; C max were (22.03±3.53)mg·L -1 and (22.58±5.94)mg·L -1 ;AUC 0～72 were (444.56±55.87)mg·h·L -1 and (433.31±58.52)mg·h·L -1 ; AUC 0～∞ were (462.95±55.35)mg·h·L -1 and (451.67±57.97)mg·h·L -1 . There were no significant difference between the main pharmacokinetic parameters of the two preparations (P0.05). The relative bioavailability of domestic tablet was (102.91±8.93)%.CONCLUSIONS This HPLC method is simple, sensitive and accurate. It is suitable for routine determination of ordinazole levels in human plasma and for its pharmacokinetic study. The result of the statistical analysis showed that the two preparations were bioequivalent.