A method is described for the simultaneous determination of zomepirac and its primary metabolite, zomepirac glucuronide, in plasma and urine. Reversed-phase liquid chromatography is used with an ion-pairing mobile phase of methanol-tetrabutylammonium hydrogen sulfate. Detection is by UV at 313 nm. Biological samples are cooled immediately, then adjusted to pH 3 to avoid zomepirac glucuronide degradation. Samples (0.5 ml) are then deproteinated with acetonitrile or acetone, the supernatant concentrated and dissolved in acetonitrile-acetate buffer, with up to one half of the sample injected onto the LC system. Recovery is greater than 70% and reproducible. The measurable concentration range is linear from 0.05 to 200 micrograms/ml. Total elution time of the assay is less than 10 min. Selectivity of zomepirac and zomepirac glucuronide is optimized. Sample preparation prior to analysis so as to prevent zomepirac glucuronide degradation is emphasized.