SIMULTANEOUS MEASUREMENT OF FLURBIPROFEN, IBUPROFEN, AND KETOPROFEN ENANTIOMER CONCENTRATIONS IN PLASMA USING L-LEUCINAMIDE AS THE CHIRAL COUPLING COMPONENT

A high performance liquid chromatographic method was developed for the quantitation of the R- and S- enantiomers of 2-arylpropionic acid nam ely flurbiprofen, ibuprofen and ketoprofen, in plasma. The procedure i nvolved extraction of drugs and internal standard from acidified plasm a into dichloromethane. After evaporation of the organic layer, the co mpounds were derivatized with L-leucinamide after addition of ethyl ch loroformate as the coupling reagent. The former diastereoisomeric amid es were chromatographied at ambient temperature on a reversed phase co lumn using 0.06M KH2PO4 - acetonitrile - triethylamine (51:49:0.1) as the mobile phase pumped at a flow rate of 1.8 ml/min. This assay allow ed determination of 0.1 mu g/ml of both R- and S- enantiomers with an acceptable precision (maximum coefficient of variation of 7.5%) using a 0.5-ml plasma sample.