Ibuprofen pharmacokinetics: use of liquid chromatography with radial compression separation

The non-steroidal antiinflammatory agent ibuprofen (Motrin) can be reliably quantitated in body fluids using high-pressure liquid chromatography with a newly developed radial compression separation system. After addition of the structural analogue flurbiprofen as internal standard, biological samples (plasma or cerebrospinal fluid) are acidified and extracted directly into benzene: isoamyl alcohol (98.5:1.5). The organic extract is separated, evaporated to dryness, reconstituted, and chromatographed using a mobile phase of water: acetonitrile (50:50, with 2.5 ml/l acetic acid), a reverse-phase C-18 radial compression cartridge, and UV detection at 229 nm. The routine sensitivity limit is 0.5 micrograms of ibuprofen per ml of sample: this can be improved with minor modifications. The coefficient of variation for replicate samples is less than 7%. Using an automated sampling system, up to 100 samples can be analyzed per 24-hour period. Application of the method to experimental and clinical pharmacokinetic studies of ibuprofen is illustrated.