Chondroitin sulfate A was covalently immobilized onto a monolithic silica epoxy column involving a Schiff base formation in the presence of ethylenediamine as a spacer and evaluated in terms of its selectivity in enantioseparation. The obtained column was utilized as a chiral stationary phase in enantioseparation of amlodipine and verapamil using a mobile phase consisting of 50 mM phosphate buffer pH 3.5 and UV detection. Sample dilution by organic solvents (preferably 25% v/v acetonitrile-aqueous solution) was applied to achieve baseline enantioresolution (Rs > 3.0) of the individual drug models within 7 min, an excellent linearity (R2 = 0.999) and an interday repeatability of 1.1% to 1.8% RSD. The performance of the immobilized column for quantification of racemate in commercial tablets showed a recovery of 86-98% from tablet matrices. Computational modeling by molecular docking was employed to investigate the feasible complexes between enantiomers and the chiral selector.

Immobilization of Chondroitin Sulfate A onto Monolithic Epoxy Silica Column as a New Chiral Stationary Phase for High-Performance Liquid Chromatographic Enantioseparation

Enantiomeric separation of six antihistamine agents was first systematically investigated on a cellulose-based chiral stationary phase (CSP), that is, cellulose tris-(3,5-dimethyl phenyl carbamate) (Chiralcel OD-RH), under the reversed-phase mode. Orphenadrine, meclizine, terfenadine, dioxopromethazine, and carbinoxamine enantiomers were completely separated under the optimized mobile phase conditions with resolutions of 5.02, 1.93, 1.68, 1.67, and 1.54, respectively. Mequitazine was partially separated with a resolution of 0.77. The influences of type and concentration of buffer salt, the pH of buffer solution, and the type and ratio of organic modifier on the chiral separation were evaluated and optimized. For a better insight into the enantiorecognition mechanisms, molecular docking was carried out via the Autodock software. The lowest binding energy and the optimal conformations of the analytes/CSP complexes were supplied, and the mechanisms of chiral recognition were determined. According to the results, the key interactions for the chiral recognition of these six analytes on CDMPC were π-π interactions, hydrophobic interactions, hydrogen bond interactions, and some special interactions.

Chiral separation and molecular simulation study of six antihistamine agents on a coated cellulose tri-(3,5-dimethylphenycarbamate) column (Chiralcel OD-RH) and its recognition mechanisms.

Development and application of an enantioselective liquid chromatography – tandem mass spectrometry method for the quantification of enantiomers to evaluate in vivo chiral inversion in beagle dog

Bioanalytical chiral chromatographic technique and docking studies for enantioselective separation of meclizine hydrochloride: Application to pharmacokinetic study in rabbits.



Polysaccharide based chiral stationary phases (CSPs) were used to perform
enantiomeric separation of Orphenadrine Citrate by Ultra-Fast Liquid Chromatography (UFLC)
technique. Trials were conducted using the polar mode, reverse phase mode and normal phase mode.
Amylose and Cellulose-based CSPs were used for the same.



Eight Amylose-based CSPs and four Cellulose-based CSPs were used in
the reverse phase mode. Five Amylose-based CSPs and two Cellulose-based CSPs were used in polar
mode. The only Cellulose-based CSP used in the normal phase mode could effectively separate
Orphenadrine Citrate enantiomers with a good resolution.



Successful enantioseparation was obtained using Chiralcel OD-H containing
Cellulose tris (3, 5-dimethylphenylcarbamate) as a chiral selector and n-hexane: Ethanol: Diethylamine
(95: 05: 0.1, v/v/v) as the mobile phase. The developed method was validated in accordance
with ICH guidelines (Q2R1).



The proposed objectives were successfully accomplished as the developed method
could effectively resolve Orphenadrine Citrate enantiomers.


Sripuram Subramanyam

Papers

Bioanalytical chiral chromatographic technique and docking studies for enantioselective separation of meclizine hydrochloride: Application to pharmacokinetic study in rabbits.

Analysis of Orphenadrine Citrate in Various Chiral Stationary Phases: A Comparative Study