Direct determination of diastereomeric carprofen glucuronides in human plasma and urine and preliminary measurements of stereoselective metabolic and renal elimination after oral administration of carprofen in man

A direct stereospecific HPLC assay for carprofen glucuronides in biologic fluids was developed that makes use of a reverse phase (C 18) gradient system, in which the mobile phase consisted of a mixture of acetonitrile and tetrabutylammonium hydroxide buffer (pH 2.5). Reference diastereomeric glucuronides of carprofen were purified from human urine after oral administration of the single enantiomers. When 0.1 ml of sample was used, the limit of detection for carprofen glucuronides was 50 ng/ml in plasma and 200 ng/ml in urine. Coefficients of variation did not exceed 12% for both intra and interday variability. This HPLC method is applicable to pharmacokinetic analysis for carprofen glucuronides in humans. After oral administration of the single enantiomers there was little indication of metabolic inversion. For the two enantiomers the apparent total and metabolic clearances were similar. The limited data available suggest that renal clearance of the (S)-glucuronide was greater than that of the (R)-glucuronide.