Enantioseparation of milnacipran enantiomers and the separation mechanism on β-cyclodextrin-based chiral stationary phases by high performance liquid chromatography

doi:10.3724/SP.J.1123.2016.09048

Abstract

Abstract:

A high performance liquid chromatography method was established for the enantiomeric separation of milnacipran enantiomers on β-cyclodextrin-based chiral stationary phases (CSPs). Chiral columns of Astec CYCLOBOND^TM I 2000 series, such as the native β-cyclodextrin (Cyclobond I 2000), acetyl-β-cyclodextrin (AC-β-CD), 2,3-dimethyl-β-cyclodextrin (DM-β-CD) and 3,5-dimethylphenyl carbamate β-cyclodextrin (DMP-β-CD), were examined under the reversed-phase mode. The effects of cyclodextrin stationary phase, mobile phase composition, pH, flow rate and column temperature on the separation of milnacipran enantiomers were investigated. The inclusion process between AC-β-CD and milnacipran enantiomers was investigated and chiral recognition mechanism was studied with molecular docking technique and binding energy calculations. The optimized conditions were as follows: the chiral stationary phase was a column of Astec CYCLOBOND^TM I 2000 AC (25 cm×4.6 mm, 5 μm), the mobile phase was acetonitrile-0.1% (v/v) pH 5.0 triethylamine acetate (TEAA) (5:95, v/v) with a flow rate of 0.4 mL/min and the detection wavelength was 220 nm. The injection volume was 10 μL and the column temperature was 25℃. The value of resolution (R_s) was 1.74 and the theoretical plates were 10125. The results suggested that hydrogen bonding ability played an important role in the chiral recognition process of milnacipran enantiomers. The developed method was rapid, effective and reproducible.

Key words: β-cyclodextrin-based chiral stationary phase, chiral separation, milnacipran, reversed-phase high performance liquid chromatography (RP-HPLC), separation mechanism

CLC Number:

O658

ZHENG Zhen, CHEN Xiujuan, ZHAO Liang, LI Wuhong, HONG Zhanying, CHAI Yifeng. Enantioseparation of milnacipran enantiomers and the separation mechanism on β-cyclodextrin-based chiral stationary phases by high performance liquid chromatography[J]. Chinese Journal of Chromatography, 2017, 35(3): 286-290.

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