Synthesis, characterization, and quantitation of para-hydroxymethadone, a metabolite of methadone in the rat

To demonstrate a p-hydroxylation process in the metabolism of methadone, we have synthesized para-hydroxymethadone and characterized it by spectroscopy (IR, 13C-NMR, mass spectrometry) and chromatography (thin layer chromatography, gas-liquid chromatography, and HPLC). para-Hydroxymethadone was isolated by HPLC from the urine of rats treated with (R,S)-methadone. para-Hydroxymethadone in the urine and in the bile represents 1.82 and 38.08%, respectively, of the administered dose. para-Hydroxymethadone does not exhibit any opioid-like activity.