Determination of a urinary epoxide metabolite of alclofenac in man.

An epoxide metabolite has been identified in the urine of normal volunteers and rheumatoid arthritis patients after the oral administration of alclofenac (1.5--4 g daily). The identification was based on a comparison of the mass spectra and gas-liquid chromatographic data for five different derivatives of the synthetic alclofenac epoxide with those obtained from urine extracts. Alclofenac epoxide was found to have a half-life of 35 hr when incubated in urine (pH5) at 37 degrees C. A quantitative analysis, based on multiple-ion monitoring, was developed; the levels of alclofenac epoxide excreted in 24 hr varied between 25 and 316 micrograms. These amounts corresponded to 0.003-0.011% of the total dose of alclofenac per day. No significant differences were observed in the concentrations of alclofenac epoxide in the urine between normal volunteers, patients with rheumatoid arthritis, and patients presenting a drug-associated rash.