THE ANALYSIS OF IBUPROFEN ENANTIOMERS IN HUMAN PLASMA AND URINE BY HIGH-PERFORMANCE LIQUID-CHROMATOGRAPHY ON AN ALPHA-1-ACID GLYCOPROTEIN CHIRAL STATIONARY-PHASE

A method for the quantitation of the enantiomers of the non-steroidal anti-inflammatory drug (NSAID) ibuprofen (IB) in human plasma and urin e was developed for pharmacokinetic studies of the individual optical antipodes. Plasma samples were acidified, extracted with organic solve nts and analysed by HPLC using an alpha(1)-acid glycoprotein column an d UV detection; elution was performed with a phosphate buffer and isop ropanol gradient; RS-flurbiprofen (FL) was used as internal standard. Calibration curves were linear in the range 0.25 - 25 mu g/ml of each IB-enantiomer. Enantiomers and internal standards were baseline separa ted. Precision and accuracy was +/- 3-6%, the limit of detection 0.1 m u g /ml, and the analytical recoveries of IB and FL 93.7 +/- 5 % and 9 4.5 +/- 4 % resp.; endogenous substances, IB metabolites and other dru gs did not interfere with the assay. Urine samples were extracted and analysed as for plasma to assay free, and after alkaline hydrolysis, t otal IB-enantiomers. The described assay is simple to perform, reprodu cible, accurate and selective for the quantitation of IB-enantiomers i n plasma and urine without precolumn derivatisation. Other chiral NSAI D drugs were baseline resolved under similar chromatographic condition s: FL, fenopfrofen and ketoprofen; the optical purities of these compo unds may be determined with high sensitivity with this HPLC system.