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 qunatitation 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 i scapabl eof quantifying ketoprefen (2 ng/mL) and iboprofen (3ng/mL) enantiomers from a 200-uL sample of synovial fluid or plasma and is particularly suitable for protein binding studies.