title: Characterization of the stereoselective metabolism of methadone and its primary metabolite via cyclodextrin capillary electrophoretic determination of their urinary enantiomers.
abstract: Using capillary zone electrophoresis with a phosphate buffer at pH 3, containing 4.3 mM hydroxypropyl-beta-cyclodextrin as chiral selector, the simultaneous separation of the enantiomers of methadone and its primary metabolite, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP), is reported. After solid-phase extraction and analysis of the reconstituted extracts in a 60 cm fused-silica capillary of 50 microns ID within about 25 min, the mean S/R enantiomeric ratio of methadone in the urines of eight patients undergoing methadone therapy is shown to be 0.653 (range: 0.502-0.842). The mean enantiomeric ratio for the metabolite is 0.630 (range: 0.517-0.729). These data document the stereoselectivity of the methadone metabolism. Finally, the EDDP/ methadone ratio is shown to vary between 0.357 and 2.917 with a mean value of 1.731. The capillary electrophoretic assay described is simple, inexpensive and neither requires any sample derivatization, nor large amounts of organic solvents or expensive separation columns.
authors.affiliation: Department of Clinical Pharmacology, University of Bern, Switzerland.
authors.forename: M
authors.initials: M
authors.lastname: Lanz
authors.forename: W
authors.initials: W
authors.lastname: Thormann
mesh_terms: D003505:Cyclodextrins; D019075:Electrophoresis, Capillary / Q000379:methods*; D006801:Humans; D008691:Methadone / Q000302:isolation & purification / Q000627:therapeutic use / Q000652:urine*; D011759:Pyrrolidines / Q000302:isolation & purification / Q000652:urine*; D013237:Stereoisomerism
chemical_list: D003505:Cyclodextrins; D011759:Pyrrolidines; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine