ENANTIOSELECTIVE SEPARATION OF METHADONE AND ITS MAIN METABOLITE IN HUMAN HAIR BY LIQUID-CHROMATOGRAPHY ION-SPRAY MASS-SPECTROMETRY

Optical isomers exhibit significant differences in their affinities fo r receptor sites, biotransformation and binding to serum and tissue pr oteins. Methadone has been used for the substitution of heroin addicts since 1964. The racemic form is used, i.e., a mixture of the biologic ally active R-form and the practically inactive S-form. To investigate methadone distribution, a chiral separation of the isomers was develo ped in human hair samples. The method involves decontamination of hair with water and acetone, pulverization in a ball mill, enzymatic hydro lysis in presence of deuterated internal standards, solid-phase extrac tion, and liquid chromatography/ion spray-mass spectrometry. Enantiose lective separation of methadone and its main metabolite, EDDP, was obt ained using an alpha1-acid glycoprotein column (100 by 4 mm ID). In al l nine specimens obtained from subjects under racemic methadone treatm ent in a detoxification center, R- and S-enantiomers of methadone and EDDP were identified with the following concentrations: 2.58-10.22, 1. 89-9.53, 0.42-1.73, and 0.40-2.10 ng/mg for R-methadone, S-methadone, R-EDDP, and S-EDDP, respectively. Results are suggestive of a predomin ance of the R-enantiomer of methadone in human hair.