Determination of ibuprofen in dog plasma by liquid chromatography and application in pharmacokinetic studies of an ibuprofen prodrug in dogs

A liquid chromatography (LC) method for the determination of ibuprofen in dog plasma is described. Chromatographic separation was performed on a Diamonsil™ C₁₈ column with a C₁₈ guard column using a binary mixture of acetonitrile and 0.02 mol/l phosphate buffer (pH 6.5) (35:65, v/v) delivered at a flow rate of 1.2 ml/min. The linear range for ibuprofen was from 1.0 to 40.0 μg/ml with a limit of quantitation of 1.0 μg/ml. Within-run accuracy and precision ranged from -0.1% to 4.0% and from 1.1% to 5.5% and between-run accuracy and precision ranged from -1.1% to 4.7% and from 1.3% to 7.0%, respectively. The mean extraction recoveries of ibuprofen determined over the concentrations of 1.0, 10.0, and 40.0 μg/ml were (100.5 ± 1.8)%, (99.8 ± 1.0)%, and (99.2 ± 2.3)%. The developed LC method greatly simplified the sample preparation and adopted mild conditions to prevent the possible hydrolysis of the prodrug and was successfully applied to the pharmacokinetic studies of an ibuprofen prodrug in dogs.