Separation and Purification of Methadone Enantiomers by Continuous- and Interval-Flow Electrophoresis

Abstract

Continuous- or free-flow electrophoresis is based upon a thin film of fluid flowing between two parallel plates. The electrolytes and the sample are continuously admitted at one end of the electrophoresis chamber and are fractionated by an array of outlet tubes at the other. Using the Octopus apparatus in a horizontal position, continuous preparative separation of methadone enantiomers in the presence of (2-hydroxypropyl)-β-cyclodextrin as a chiral selector was investigated under conditions of continuous-flow zone electrophoresis and continuous-flow isotachophoresis. The enantiomeric composition of methadone in the collected fractions was assessed by chiral capillary electrophoresis and circular-dichroism spectroscopy. In both electrophoretic 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 obtained. Operating the Octopus apparatus with interrupted buffer flow during electrophoresis, a process termed interval-flow electrophoresis, resulted in complete separation of milligram quantities of the two methadone enantiomers. Furthermore, commencing with racemic methadone, continuous multistage isotachophoretic processing is shown to be suitable to purify (R)-(-)-methadone, the enantiomer with higher pharmacological activity, on a mg/h scale and at a mM concentration in the collected product stream.

Chiral separation by chromatographic and electromigration techniques. A Review

“…Kaniansky et al [477] and Hoffmann et al [478] described ITP -systems for preparative isolation and purification of enantiomers. Coupled ITP-CZE systems for sample pretreatment and chiral separation were developed by Dankova et al [479], Fanali et al [480] and Tousaint et al [481].…”

Purification of low‐concentration phenazine‐1‐carboxylic acid from fermentation broth of Pseudomonas sp. M18 via free flow electrophoresis with gratis gravity

“…As for scale-up purification, the preparative HPLC would be applied as the primary available technique for PCA preparation [10]. However, as a result of high cost of stationary phase, large consumption and tough recycling of mobile phase, and especially the batch procedure in contrast to a continuous one, it was difficult for the chromatographic method to control a separation process [11].…”

“…Thus, the samples could be isolated laterally according to their mobilities in FFE chamber. To date, there have been a few reports about FFE-based separation of enantiomers' separations [11,13] and multi-charged chemicals [14,15]. FFE had numerous advantages, such as high recovery, mild environment for separation of sample with biological activity, lower cost due to consumption of mobile phase, and controllable continuous process.…”

Advances in synthetic optically active condensation polymers - A review

“…Both naturally occurring and synthetic chiral polymers and supramolecules have found prosperous applications in chiral chromatographic separations and shown potential uses in chiral catalytic systems, liquid crystals in ferroelectric and nonlinear optical (NLO) devices, electrodes for enantioselective recognition for performing bioelectro synthesis, microwave absorbents, membrane separation technology, optical switches, biomedical equipments and optoelectronics application. A direct and efficient approach for synthesizing chiral polymers is to introduce chiral elements into the macromolecule backbone or the side chains [6][7][8][9][10][11][12][13][14]. In the history of synthetic polymer chemistry, it seems that one of the most challenging tasks is to construct functional polymeric systems and optically active synthetic polymers that will be as effective as those in living systems [15][16][17][18].…”