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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
Author(s) -
Kelly Tamsin,
Doble Philip,
Dawson Michael
Publication year - 2003
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.200305418
Subject(s) - enantiomer , chemistry , capillary electrophoresis , chromatography , cyclodextrin , stereoselectivity , resolution (logic) , stereochemistry , organic chemistry , artificial intelligence , computer science , catalysis
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 β‐cyclodextrin (βCD) 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 m M heptakis‐(2,6‐di‐ O‐ methyl)‐β‐cyclodextrin (DMβCD) in 100 m M 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 βCD 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 m M (2‐hydroxy)propyl‐β‐cyclodextrin (HPβCD) in 100 m M 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.