Enantiospecific gas chromatographic-mass spectrometric procedure for the determination of ketoprofen and ibuprofen in synovial fluid and plasma: application to protein binding studies

A method for the enantiospecific quantitation of two commonly prescribed non-steroidal anti-inflammatory drugs (ketoprofen and ibuprofen) is described. The method involves formation of a mixed anhydride of the drug with ethylchloroformate and subsequent conversion to an amide by reaction with optically active amphetamine. The subsequently formed diastereomers are separated by gas chromatography-mass spectrometry using selected-ion monitoring. The assay is capable of quantifying ketoprofen (2 ng/ml) and ibuprofen (3 ng/ml) enantiomers from a 200-μl sample of synovial fluid or plasma and is particularly suitable for protein binding studies.