Simultaneous determination of acetylmethadol and its active riotransformation products in human biofluids

A method employing solvent extraction and gas-liquid chromatography has been developed for the quantitative determination of acetylmethadol simultaneously with its two major biotransformation products, noracetylmethadol and dinoracetylmethadol. Noracetylmethadol and dinoracetylmethadol are analyzed following their conversion to the corresponding amides. The amide structure is confirmed by the use of chemical ionization mass spectroscopy and infrared spectroscopy. The method can be used to determine the concentration of acetylmethadol and these compounds in plasma samples from acetylmethadol maintenance subjects. Methadol and normethadol do not attain neasurable plasma levels. Urine contains predominantly noracetylmethadol and dinoracetylmethadol. Evidence was also obtained for the urinary excretion of acetylmethadol, methadol and normethadol. A mean quantity equal to 28% of the administered dose was excreted in the urine of a 48-h dosing interval as acetylmethadol and metabolites.