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 Review on Chiral Columns/Stationary Phases for HPLC

The chiral separation of pharmaceutical molecules and their precursors is one of the important areas of application of HPLC in pharmaceutical analysis for obtaining enantiomerically pure drug. The latter procedures include the use of so-called chiral selectors to enantio-selectively recognise and isolate the enantiomer. The direct approaches, i.e. those which do not derivate the compound of interest before separation, are addressed in detail, since they are now the most common approaches. The role of stereochemistry in medicinal products is being given greater emphasis to medical practice. For physicians to make conscious choice about the use of single-enantiomered medicinal products, basic knowledge is required. For few treatments single-enantiomer formulations can provide more selectivity than a combination of enantiomers in their biological purposes, enhanced therapeutic indexes and/or better pharmacokinetics. This highlights the possible biological and pharmacological variations between the two drug enantiomers and underlines the clinical experience of individual enantiomers. Particular emphases have been put on chiral separation by HPLC on chiral stationary phases (CSPs). Chiral derivatization reagents (CDRs) are optically pure reagent on reaction with drugs forms a pair of diastereoisomers that can be separated on conventional achiral phase. In Chiral mobile phase additive (CMPA) method, the stationary phase is achiral and the chiral selector is dissolved during the mobile phase. Interaction with the analyte’s enantiomer leads to the formation of transient diastereomeric complexes that are separated by their affinity towards mobile/stationary phase. Separation mechanisms and method development for chiral molecules using these phases are discussed in this review.

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.

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.