HIGH PERFORMANCE LIQUID CHROMATOGRAPHIC ASSAY FOR ACECLOFENAC IN PLASMA AND ITS PHARMACOKINETICS IN DOGS

A sensitive and simplified high performance liquid chromatographic procedure has been developed for the quantification of aceclofenac and its major metabolite in dog plasma. The recovery of aceclofenac was 91.3%～96.9%. The relative standard deviation was 3.69%～8.13%. The calibration curve was linear in the range from 0.050 μg·ml^-1 to 51.2 μg·ml^-1 with γ=0.9998. The detection limit of the method is 10 ng·ml^-1 for aceclofenac. Plasma concentrations of both aceclofenac and its major metabolite were simultaneously determined. After oral medication of aceclofenac to dogs at the dose of 2.5 mg·kg^-1, the drug was absorbed rapidly and reached its peak level in plasma at about 12 min.The plasma drug concentration-time course conformed to a 2-compartment open model with a first order absorption. The mean value of T_1/2α and T_1/2β for aceclofenac were 2.5 min and 137 min respectively. Plasma diclofenac concentration, a major metabolite of aceclofenac, reached its maximum at about 110 min, the mean Cmax for diclofenac was 3.2 μg·ml^-1. The mean terminal elimination half-life for diclofenac was 140 min.