Enantioseparation of chiral pharmaceuticals by vancomycin‐bonded stationary phase and analysis of chiral recognition mechanism. Issue 3 (24th January 2019)

• Record Type: Journal Article
• Authors: Li, Jiaxi; Liu, Ruixia; Wang, Liyang; Liu, Xiaoling; Gao, Hongjie
• Is Part Of: Chirality. Volume 31:Issue 3(2019)
• Page Start: 236
• Page End: 247
• Publication Date: 2019-01-24
• Subjects: chiral pharmaceutical -- chiral recognition mechanism -- enantioseparation -- HPLC‐vancomycin CSP -- molecular docking -- thermodynamic analysis; Chirality -- Periodicals; Pharmaceutical chemistry -- Periodicals; 541.22
• DOI: 10.1002/chir.23052
• Languages: English
• ISSNs: 0899-0042

Abstract

Abstract: The drug chirality is attracting increasing attention because of different biological activities, metabolic pathways, and toxicities of chiral enantiomers. The chiral separation has been a great challenge. Optimized high‐performance liquid chromatography (HPLC) methods based on vancomycin chiral stationary phase (CSP) were developed for the enantioseparation of propranolol, atenolol, metoprolol, venlafaxine, fluoxetine, and amlodipine. The retention and enantioseparation properties of these analytes were investigated in the variety of mobile phase additives, flow rate, and column temperature. As a result, the optimal chromatographic condition was achieved using methanol as a main mobile phase with triethylamine (TEA) and glacial acetic acid (HOAc) added as modifiers in a volume ratio of 0.01% at a flow rate of 0.3 mL/minute and at a column temperature of 5°C. The thermodynamic parameters (eg, ΔH, ΔΔH, and ΔΔS ) from linear van 't Hoff plots revealed that the retention of investigated pharmaceuticals on vancomycin CSP was an exothermic process. The nonlinear behavior of ln k′ against 1/ T for propranolol, atenolol, and metoprolol suggested the presence of multiple binding mechanisms for these analytes on CSP with variation of temperature. The simulated interaction processes between vancomycin and pharmaceutical enantiomers using molecular docking technique and binding energy calculations indicated that the calculated magnitudes of steady combination energy ( ΔG ) coincided with experimental elution order for most of these enantiomers. Abstract : Enantioseparation of six pharmaceuticals was performed by HPLC method based on vancomycin CSP. Mobile phase additives, flow rate, and column temperature was optimized. Using binding energy calculations and molecular docking, thermodynamic properties of enantiomer retention onto CSP and chiral recognition mechanisms were explained.