GLC determination of ibuprofen [dl-2-(p-isobutylphenyl)propionic acid] enantiomers in biological specimens

To study the behavior of the d- and l-isosomers of ibuprofen in humans, a method for the determination of the individual enantiomers in plasma and urine was required. A specific procedure was developed based on (a) benzene extraction of the acidified specimens, (b) TLC of the benzene extract residue, (c) formation of the l-α-methylbenzylamides of the materials eluted from the chromatograms, and (d) quantification of the resulting diastereoisomeric amides by GLC in conjunction with flame-ionization detection. When using a 1-ml aliquot of the specimen, the method is sensitive to 1 ug of each enantiomer/ml of plasma or urine. As compared to simple aqueous solutions, the average recoveries of the enantiomers from plasma and urine ranged from 94 to 96%. Mass spectrometric analyses, in conjunction with GLC, confirmed the specificity of the method for the intact enantiomers. The procedure was applied successfully to drug absorption studies in humans. After oral administration of the racemic mixture, the predominant enantiomer in peripheral circulation and excreted in urine was of the d-configuration.