title: Chiral separation of methadone, 2-ethylidene- 1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) by capillary electrophoresis using cyclodextrin derivatives.
abstract: A stereoselective method was developed for the simultaneous determination of methadone and its two major metabolites, 2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine (EDDP) and 2-ethyl-5-methyl-3,3-diphenyl-1-pyrroline (EMDP) by capillary electrophoresis. Five beta-cyclodextrin (betaCD) background electrolyte (BGE) additives were evaluated for resolution efficiency. The conditions for baseline resolution of each of the three enantiomer pairs was determined to be 1 mM heptakis-(2,6-di-O-methyl)-beta-cyclodextrin (DMbetaCD) in 100 mM phosphate at pH 2.6. This method represents the first successful method for the resolution of the six enantiomers associated with the metabolism of methadone. The utilisation of doubly coated capillaries in conjunction with betaCD derivatives for a faster separation of the methadone-related enantiomers is also reported. The coated capillaries were prepared using a polycation of poly(diallyldimethylammonium chloride) (PDDAC) and a polyanion of dextran sulfate. Baseline resolution of the methadone enantiomers was achieved with a BGE of 8 mM (2-hydroxy)propyl-beta-cyclodextrin (HPbetaCD) in 100 mM phosphate at pH 2.6. The migration times for the stereoselective methadone separation were approximately 4 min, which represented a reduction by a factor of approximately three, compared to that attained using analogous conditions with the uncoated capillary.
authors.affiliation: Centre for Forensic Science, Faculty of Science, University of Technology, Sydney, (UTS), Sydney, Australia.
authors.forename: Tamsin
authors.initials: T
authors.lastname: Kelly
authors.affiliation: Centre for Forensic Science, Faculty of Science, University of Technology, Sydney, (UTS), Sydney, Australia.
authors.forename: Philip
authors.initials: P
authors.lastname: Doble
authors.affiliation: Centre for Forensic Science, Faculty of Science, University of Technology, Sydney, (UTS), Sydney, Australia.
authors.forename: Michael
authors.initials: M
authors.lastname: Dawson
mesh_terms: D019075:Electrophoresis, Capillary / Q000379:methods*; D006838:Hydrocarbons / Q000302:isolation & purification*; D008691:Methadone / Q000302:isolation & purification*; D011759:Pyrrolidines / Q000302:isolation & purification*; D013237:Stereoisomerism
chemical_list: D006838:Hydrocarbons; D011759:Pyrrolidines; D008691:Methadone; C010724:2-ethylidene-1,5-dimethyl-3,3-diphenylpyrrolidine