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 for receptor sites, biotransformation and binding to serum and tissue proteins. Methadone has been used for the substitution of heroin addicts since 1964. The racemic form is used, i.e., a mixture of the biologically active R-form and the practically inactive S-form. To investigate methadone distribution, a chiral separation of the isomers was developed in human hair samples. The method involves decontamination of hair with water and acetone, pulverization in a ball mill, enzymatic hydrolysis in presence of deuterated internal standards, solid-phase extraction, and liquid chromatography/ion spray-mass spectrometry. Enantioselective separation of methadone and its main metabolite, EDDP, was obtained using an alpha1-acid glycoprotein column (100 by 4 mm ID). In all nine specimens obtained from subjects under racemic methadone treatment 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 predominance of the Renantiomer of methadone in human hair.
Kintz
P
P
Toxicology Laboratory, Institut de Médecine Légale, Strasbourg, France.
Eser
H P
HP
Tracqui
A
A
Moeller
M
M
Cirimele
V
V
Mangin
P
P
D002853:Chromatography, Liquid; D006197:Hair / Q000737:chemistry*; D006801:Humans; D008691:Methadone / Q000302:isolation & purification* / Q000378:metabolism*; D009961:Orosomucoid; D011759:Pyrrolidines / Q000302:isolation & purification*; D018629:Spectrometry, Mass, Secondary Ion; D013237:Stereoisomerism
D009961:Orosomucoid; D011759:Pyrrolidines; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine