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Characterization of the stereoselective metabolism of methadone and its primary metabolite via cyclodextrin capillary electrophoretic determination of their urinary enantiomers
Author(s) -
Lanz Matthias,
Thormann Wolfgang
Publication year - 1996
Publication title -
electrophoresis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.666
H-Index - 158
eISSN - 1522-2683
pISSN - 0173-0835
DOI - 10.1002/elps.1150171223
Subject(s) - enantiomer , capillary electrophoresis , metabolite , chemistry , chromatography , stereoselectivity , cyclodextrin , primary metabolite , metabolism , drug metabolism , urinary system , biochemistry , stereochemistry , biology , endocrinology , catalysis
Using capillary zone electrophoresis with a phosphate buffer at pH 3, containing 4.3 nM hydroxypropyl‐β‐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 μm 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.