Identification and quantitative determination of some metabolites of methadone, isomethadone and normethadone

Abstract
Isomethadone and normethadone are metabolized by microsomal preparations of guinea-pig liver to yield 2-ethyl-1,4-dimethyl-3,3-diphenyl-1-pyrroline and 2-ethyl-1-methyl-3,3-diphenyl-1-pyrroline respectively. The structures of the pyrrolines were established (by comparison with the pyrroline derived from methadone) by thin-layer chromatography and by infrared and nuclear magnetic resonance spectral data. Methadone, isomethadone and normethadone are also metabolized to the corresponding N-oxides. A gas chromatographic procedure for the quantitative determination of unchanged drugs, cyclic metabolites and N-oxides of methadone, isomethadone and normethadone in microsomal homogenates is described. The N-oxides were reduced before analysis.