Development of capillary gas chromatographic-mass spectrometric methodology for the simultaneous determination of ibuprofen and [ar-2H4]ibuprofen in serum: demonstration of kinetic equivalence in the beagle.

A capillary gas chromatographic-mass spectrometric method for the determination of ibuprofen and tetra-deuterated ibuprofen in serum is described. Ibuprofen, [ar-2H4]ibuprofen and the internal standard, [ar-2H4,3,3,3-2H3]ibuprofen, are extracted (after acidification) from serum onto a cross-linked styrene divinyl benzene resin by an automated sample processor. After elution and evaporation of the organic phase, samples are reconstituted with solvent and analyzed without derivatization by capillary gas chromatography-mass spectrometry. This methodology was used to evaluate possible kinetic isotope effects after the coadministration of an equimolar mixture of ibuprofen and the deuterium-labeled covariant in the beagle. No significant differences in absorption or elimination were observed.