Chiral Monolithic Silica-Based HPLC Columns for Enantiomeric Separation and Determination: Functionalization of Chiral Selector and Recognition of Selector-Selectand Interaction

This review draws attention to the use of chiral monolithic silica HPLC columns for the enantiomeric separation and determination of chiral compounds. Properties and advantages of monolithic silica HPLC columns are also highlighted in comparison to conventional particle-packed, fused-core, and sub-2-µm HPLC columns. Nano-LC capillary monolithic silica columns as well as polymeric-based and hybrid-based monolithic columns are also demonstrated to show good enantioresolution abilities. Methods for introducing the chiral selector into the monolithic silica column in the form of mobile phase additive, by encapsulation and surface coating, or by covalent functionalization are described. The application of molecular modeling methods to elucidate the selector–selectand interaction is discussed. An application for enantiomeric impurity determination is also considered.

Enantioselective Chromatographic Analysis of Formoterol Fumarate using Chiral Mobile Phase Additives and Achiral Core-Shell Column

<p>A simple, robust, cost-effective, and rapid RP-HPLC method was developed for the separation of enantiomers of formoterol. The separation was achieved by the chiral mobile phase additive technique on an achiral column. Formoterol is a bronchodilator that consists of 50:50 S, S-formoterol and R, R-formoterol. The bronchodilator activity is attributed to R, R-formoterol. Hence, it is important to develop a method to separate the enantiomers of formoterol. Various factors affecting enantiomeric resolution were investigated and optimized. The enantiomers of formoterol were successfully separated with a resolution of 2.57 with a run-time of 9 minutes. The method was validated in accordance with ICH guidelines. The validated method was successfully applied to the marketed formulation of arformoterol. </p>

Enantioselective Chromatographic Analysis of Formoterol Fumarate using Chiral Mobile Phase Additives and Achiral Core-Shell Column

<p>A simple, robust, cost-effective, and rapid RP-HPLC method was developed for the separation of enantiomers of formoterol. The separation was achieved by the chiral mobile phase additive technique on an achiral column. Formoterol is a bronchodilator that consists of 50:50 S, S-formoterol and R, R-formoterol. The bronchodilator activity is attributed to R, R-formoterol. Hence, it is important to develop a method to separate the enantiomers of formoterol. Various factors affecting enantiomeric resolution were investigated and optimized. The enantiomers of formoterol were successfully separated with a resolution of 2.57 with a run-time of 9 minutes. The method was validated in accordance with ICH guidelines. The validated method was successfully applied to the marketed formulation of arformoterol. </p>

A Simple and Cost-Effective Synthesis of Sulfated β-Cyclodextrin and Its Application as Chiral Mobile Phase Additive in the Separation of Cloperastine Enantiomers

A new, simple and cost-effective method for the synthesis of sulfated beta-cyclodextrin (S-β-CD), one of the most widely used chiral mobile phase additive, using sulfamic acid as sulfonating agent has been described. The method was optimized and the acquired product was characterized and compared with a marketed Sigma Aldrich sulfated beta-cyclodextrin (S-β-CD1). Beta cyclodextrin (β-CD), hydroxypropyl beta-cyclodextrin (HP-β-CD), S-β-CD1 and S-β-CD2 were evaluated as chiral mobile phase additives (CMPAs) for the enantiomeric separation of cloperastine, an antitussive agent, using reversed-phase HPLC. Under the optimized conditions, a resolution of 3.14 was achieved within 15 minutes on an achiral Kromasil C₈ (150 x 4.6 mm, 5 µ) column with a mobile phase of 5mM monopotassium phosphate containing 10mM S-β-CD3 pH 3 and 45% methanol with a run time of 15 min. The method utilizing S-β-CD3 as CMPA was validated as per ICH guidelines and applied for the quantitative determination of cloperastine enantiomers in active pharmaceutical ingredients and pharmaceutical formulations. The selectivity changes imparted by S-β-CD were proven to be beneficial for chiral separation. The chiral recognition mechanism and elution order of the reported enantiomers were determined by simulation studies. It was observed that inclusion complex formation and hydrogen bonding are the major forces for the chiral resolution.