Enantioseparation of racemic aminoglutethimide using asynchronous simulated moving bed chromatography.

The separation of aminoglutethimide enantiomers by the continuous multicolumn chromatographic processes were investigated experimentally and theoretically, where the columns were packed with cellulose tris 3,5-dimethylphenyl-carbamate stationary phase (brand name Chiralcel OD) and mobile phase was a mixture of n-hexane and ethanol with monoethanolamine additive. The continuous enantioseparation processes included a synchronous shifting process (SMB) and an asynchronous shifting process (VARICOL), which allowed reducing the column number (here from six-column SMB to five-column VARICOL process). Transport-dispersive model with the consideration of both intraparticle mass transfer resistance and axial dispersion was adopted to design and optimize the operation conditions for the separation of aminoglutethimide enantiomers by SMB process and VARICOL process. According to the optimized operation conditions, experiments were carried out on VARICOL-Micro unit using five-column VARICOL process with 1/1.5/1.5/1 configuration and six-column SMB process with 1/2/2/1 configuration. Products of R-aminoglutethimide (R-AG) enantiomer and S-aminoglutethimide (S-AG) enantiomer with more than 99.0% purity were obtained continuously from extract stream and raffinate stream, respectively. Furthermore, the experiemntal data obtained from five-column VARICOL process were compared with that from six-column SMB process, the feasibility and efficiency for the separation of guaifenesin enantiomers by VARICOL processes were evaluated.

[Chromatographic separation of aminoglutethimide enantiomers on cellulose tris(3,5-dimethylphenylcarbamate) chiral stationary phase].

Aminoglutethimide (AG) has been used clinically as a drug in the treatment of hormone-dependent metastatic breast cancer. It was reported that S-(-)-AG enantiomer had small activity and sometimes might cause side effects. Therefore, it was of great significance to obtain the high-purity R-(+)-AG by enantioseparation. In this work, aminoglutethimide enantiomers were separated by high performance liquid chromatography (HPLC) using an analytical column which was packed with cellulose tris(3,5-dimethylphenylcarbamate) stationary phase (Chiralcel OD-H). The solubilities of racemic AG in two different solvent compositions, n-hexane/ethanol and n-hexane/isopropanol, were measured, separately. The effects of alcohol content and monoethanolamine additive on the separation performance of racemic AG by HPLC were investigated. According to the experiments, n-hexane-ethanol (30:70, v/v) with 0.1% monoethanolamine additive was selected as the mobile phase. The separation factor, resolution, asymmetry factor, number of theoretical plates and maximum column capacity were measured and analyzed for the chromatographic separation of racemic AG at a flow-rate of 0. 6 mL/min and column temperature of 25-40 °C, with Chiralcel OD-H as stationary phase and n-hexane-ethanol (30:70, v/v) with 0. 1% monoethanolamine as mobile phase. This work provides the basic information of chromatographic separation for the batch and continuous production of aminoglutethimide enantiomers.

Experiment and modeling for the separation of guaifenesin enantiomers using simulated moving bed and Varicol units.

The separation of guaifenesin enantiomers by both simulated moving bed (SMB) process and Varicol process was investigated experimentally and theoretically, where the columns were packed with cellulose tris 3,5-dimethylphenylcarbamate (Chiralcel OD) stationary phase and a mixture of n-hexane and ethanol was used as mobile phase. The operation conditions were designed based on the separation region with the consideration of mass transfer resistance and axial dispersion, and the experiments to separate guaifenesin enantiomers were carried out on VARICOL-Micro unit using SMB process with the column configuration of 1/2/2/1 and Varicol process with the column configuration of 1/1.5/1.5/1, respectively. Single enantiomer with more than 99.0% purity was obtained in both processes with the productivity of 0.42 genantiomer/dcm(3) CSP for SMB process and 054 genantiomer/dcm(3) CSP for Varicol process. These experimental results obtained from SMB and Varicol processes were compared with those reported from literatures. In addition, according to the numerical simulation, the effects of solid-film mass transfer resistance and axial dispersion on the internal profiles were discussed, and the effect of column configuration on the separation performance of SMB and Varicol processes was analyzed for a few columns system. The feasibility and efficiency for the separation of guaifenesin enantiomers by SMB and Varicol processes were evaluated.

Experiment and modeling for the separation of trans-stilbene oxide enantiomers on Chiralcel OD preparative column.

The chromatographic enantioseparation of trans-stilbene oxide (TSO) was studied experimentally and theoretically, where the preparative column was packed with 20 µm Chiralcel OD stationary phase and hexanes/2-propanol were used as mobile phase. The bed porosity, axial dispersion coefficient, mass transfer coefficient and the column efficiency were determined according to the pulse response experiments. The adsorption equilibrium isotherms of single and racemic mixture of trans-stilbene oxide were measured by the frontal analysis, the linear-Langmuir isotherm model was used to fit the experimental data, and the relative parameters were estimated for the competitive adsorption equilibrium of TSO enantiomers. Elution profiles were measured for the separation of TSO enantiomers on Chiralcel OD preparative column, and the experimental data were compared with the simulated results predicted by the mathematical model that accounted for axial dispersion and linear driving force mass transfer model. The adsorption equilibrium and kinetic information obtained in this work are useful for the scale up and optimization of both batch and continuous chromatographic enantioseparation systems.