Enantioseparation of Cinacalcet, and its Two Related Compounds by HPLC with Self-Made Chiral Stationary Phases and Chiral Mobile Phase Additives

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Author(s): Canyu Yang, Ji Li, Yanyun Yao, Chen Qing, Baochun Shen.

Journal Name: Current Pharmaceutical Analysis


Background: Cinacalcet is one of the second-generation calcimimetics which consists of a chiral center. The pharmacological effect of R-cinacalcet is 1000 times greater than that of the Scinacalcet. As mentioned in many literatures, 1-(1-naphthyl)ethylamine is used as the starting material for the synthesis of cinacalcet. The absolute structure of cinacalcet is influenced by the starting materials. Methods: we present the chiral separation of cinacalcet and its starting material, 1-(1-naphthyl) ethylamine along with one of its intermediates, N-(1-(naphthalen-1-yl) ethyl)-3- (3-(trifluoromethyl) phenyl) propanamide by high-performance liquid chromatography with chiral stationary phase and chiral mobile phase additives. Results: On vancomycin and cellulose tri 3,5-dimethylphenylcarbamate) chiral stationary phase, cinacalcet and 1-(1-naphthyl)ethylamine achieved enantioseparation under normal phase with addition of triethylamine additives, respectively. Meanwhile, 1-(1-naphthyl)ethylamine and N-(1-(naphthalen-1- yl)ethyl)-3-(3-(trifluoromethyl) phenyl) propanamide achieved enantioseparation on 1-napthalene vancomycin chiral stationary phase using D-tartaric acid, diethyl L-tartrate and diethyl D-tartrate as chiral mobile phase additives. Conclusion: The chiral recognition in our experiment was based on the hydrogen-bonding, dipoledipole and π-π interactions among the solutes, chiral stationary phases and chiral mobile phase additives. In addition, the space adaptability of chiral stationary phases also affected the separation efficacy.

Keywords: Chiral mobile phase additive, Chiral stationary phase, Cinacalcet, Enantioseparation, Recognition mechanisms, HPLC

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(E-pub Ahead of Print)
DOI: 10.2174/1573412914666180518105046