Separation and purification of methadone enantiomers by continuous- and interval-flow electrophoresis

Continuous- or free-now electrophoresis is based upon a thin film of fluid flowing between two parallel plates. The electrolytes and the sample are co ntinuously admitted at one end of the electrophoresis chamber and are fract ionated bq an array of outlet tubes at the other. Using the Octopus apparat us in a horizontal position, continuous preparative separation of methadone enantiomers in the presence of (2-hydroxypropyl)-beta-cyclodextrin as a ch iral selector was investigated under conditions of continuous-flow zone ele ctrophoresis and continuous-now isotachophoresis. The enantiomeric composit ion of methadone in the collected fractions was assessed by chiral capillar y electrophoresis and circular-dichroism spectroscopy, In both electrophore tic modes, partial separation of the two enantiomers with an enrichment of about 80% and a throughput of 10-20 mg of racemic methadone per hour was ob tained. Operating the Octopus apparatus with interrupted buffer now during electrophoresis, a process termed interval-now electrophoresis, resulted in complete separation of milligram quantities of the two methadone enantiome rs, Furthermore, commencing with racemic methadone, continuous multistage i sotachophoretic processing is shown to be suitable to purify (R)-(-)-methad one, the enantiomer with higher pharmacological activity, on a mg/h scale a nd at a mM concentration in the collected product stream.