Determination of morphine- N-methyl- 14C oxide in biological materials, its excretion and metabolites in the rat

Abstract

A method for determination of morphine- N-methyl- 14C oxide in biological materials has been described which gave approximate recoveries of N-oxide as 94, 82, and 77% from urine or plasma, liver and brain tissue, respectively. On subcutaneous injection of 20 mg/kg of morphine- N-methyl- 14C oxide, male Sprague-Dawley rats excreted 80.6–91.5% of total radioactivity in urine and feces, 19.6–41.2% as free N-oxide, 6.2–24.3% as free morphine and 3.6–6.9% as morphine-3-glucuronide. Column and thin-layer chromatography established morphine, morphine-3-glucuronide, and normorphine (5–10%) as princlpal urinary metabolites of morphine N-oxide in the rat. Evidence for the formation of N-oxide as a metabolite of morphine in the central nervous system of rats was not obtained. Morphine N-oxide can be converted nonenzymatically to morphine and normorphine by ferrous iron and cysteine.