Pre-column Derivatization and Separation of Diastereomeric-Derivatives of Racemic Mexiletine and Confirmation of Elution Order and Molecular Configuration

Abstract

Present study describes the synthesis of cyanuric chloride based four active chiral reagents (ACRs) and their application in the enantiomeric separation of (RS)-mexiletine. Herein, four cyanuric chloride-based ACRs were prepared by introducing L-proline derivatives under nucleophilic substitution reaction. The synthesized ACRs were characterized by different spectroscopic techniques. Racemic mexiletine hydrochloride was used for the enantio-recognition study. All the four ACRs were used to convert (RS)-mexiletine into related diastereomeric derivatives and then separated on the C18-column of RP-HPLC. The different parameters such as sample amount, the concentration of mobile phase, organic modifier and pump pressure were varied to optimize separation conditions. The energy-minimized structures of synthesized diasteromeric derivatives (DDs) were developed using DFT calculations. The validation study was conducted for the developed method and correlation-coefficient, calibration range, LOD and LOQ calculated. The stability and recovery were calculated by inter and intraday assay.

Sensitive Detection and Enantioseparation of β-Blockers with Quinoline Based Active Chiral Reagents using HPLC: Separation Mechanism and DFT Modelling

“…Acetonitrile was a better organic modifier for the eluting phase due to higher polarity, low density and low UV cut-off. Also, in the presence of acetonitrile, the peaks appear in chromatograms were sharper [26,31]. The eluting phase at 3.5 pH gives better separation rather than the lower or higher acidic eluting phase.…”

Synthesis of Quinoline-based New Organic Chemosensors and its Application in Fluorophoric Detection of Metal-ions in Environmental Samples and Confirmation of Results using Molecular Modelling: A Complete Study

“…The DFT calculations were performed to develop the lowest energy structures of the ligands (QL1 and QL2) and the metal complexes of the ligands with Cu 2+ ions (Fig. 3a-b) [37,38]. The difference in the energy-gap between the homo and lumo orbitals was found 4.45 eV and 4.21 eV, respectively, for QL1 and QL2.…”

Synthesis of a Series of Quinoline-Based New Chiral Reagent and its Application in Separation of Racemic Mexiletine followed by Liquid Chromatography and Confirmation of Results Using Molecular Modelling; A Complete Study

“…Still, the results with acetonitrile were better due to its low viscosity and low UV cut-off and thus doesn't interfere in the detection of diastereomers. Acetonitrile provides sharp peaks and lower elution time for diastereomers compared to other organic solvents [28,29]. For the current study, the different flow-rates (0.25 to 1.5 mL/min) of the eluting phase for the RP-HPLC system were investigated.…”