Chiral Mobile-Phase Additives in HPLC Enantioseparations

2019 ◽  
pp. 81-91
Author(s):  
Lushan Yu ◽  
Shengjia Wang ◽  
Su Zeng
Keyword(s):  
Mobile Phase ◽  
Mobile Phase Additives ◽  
Chiral Mobile Phase Additives

scholarly journals Quality-by-Design Is a Tool for Quality Assurance in the Assessment of Enantioseparation of a Model Active Pharmaceutical Ingredient

2020 ◽  
Vol 13 (11) ◽  
pp. 364
Author(s):  
Dina Aboushady ◽  
Maria Kristina Parr ◽  
Rasha S. Hanafi
Keyword(s):  
Quality Assurance ◽  
Analytical Method ◽  
Mobile Phase ◽  
Method Development ◽  
Quality By Design ◽  
Active Pharmaceutical Ingredient ◽  
Binding Interaction ◽  
Mobile Phase Additives ◽  
Central Composite Designs ◽  
Chiral Mobile Phase Additives

The design of experiments (DoE) is one of the quality-by-design tools valued in analytical method development, not only for cost reduction and time effectiveness, but also for enabling analytical method control and understanding via a systematic workflow, leading to analytical methods with built-in quality. This work aimed at using DoE to enhance method understanding for a developed UHPLC enantioseparation of terbutaline (TER), a model chiral drug, and to define quality assurance parameters associated with using chiral mobile phase additives (CMPA). Within a response surface methodology workflow, the effect of different factors on both chiral resolution and retention was screened and optimized using Plackett-Burman and central composite designs, respectively, followed by multivariate mathematical modeling. This study was able to delimit method robustness and elucidate enantiorecognition mechanisms involved in interactions of TER with the chiral modifiers. Among many CMPAs, successful TER enantioresolution was achieved using hydroxypropyl β-cyclodextrin (HP-β-CD) added to the mobile phase as 5.4 mM HP-β-CD in 52.25 mM ammonium acetate. Yet, limited method robustness was observed upon switching between the different tested CMPA, concluding that quality can only be assured with specific minimal pre-run conditioning time with the CMPA, namely 16-column volume (60 min at 0.1 mL/min). For enantiorecognition understanding, computational molecular modeling revealed hydrogen bonding as the main binding interaction, in addition to dipole-dipole inside the CD cavity for the R enantiomer, while the S enantiomer was less interactive.

Enantioseparation of Cinacalcet, and its Two Related Compounds by HPLC with Self-Made Chiral Stationary Phases and Chiral Mobile Phase Additives

2019 ◽  
Vol 15 (2) ◽  
pp. 200-209
Author(s):  
Canyu Yang ◽  
Ji Li ◽  
Yanyun Yao ◽  
Chen Qing ◽  
Baochun Shen
Keyword(s):  
Stationary Phase ◽  
Mobile Phase ◽  
High Performance ◽  
Chiral Stationary Phase ◽  
Stationary Phases ◽  
Chiral Stationary Phases ◽  
Starting Material ◽  
Mobile Phase Additives ◽  
Chiral Mobile Phase Additives ◽  
Related Compounds

Background: Cinacalcet is one of the second-generation calcimimetics which consists of a chiral center. The pharmacological effect of R-cinacalcet is 1000 times greater than that of the Scinacalcet. As mentioned in many literatures, 1-(1-naphthyl)ethylamine is used as the starting material for the synthesis of cinacalcet. The absolute structure of cinacalcet is influenced by the starting materials. Methods: We present the chiral separation of cinacalcet and its starting material, 1-(1-naphthyl) ethylamine along with one of its intermediates, N-(1-(naphthalen-1-yl) ethyl)-3- (3-(trifluoromethyl) phenyl) propanamide by high-performance liquid chromatography with chiral stationary phase and chiral mobile phase additives. Results: On vancomycin and cellulose tri 3,5-dimethylphenylcarbamate) chiral stationary phase, cinacalcet and 1-(1-naphthyl)ethylamine achieved enantioseparation under normal phase with addition of triethylamine additives, respectively. Meanwhile, 1-(1-naphthyl)ethylamine and N-(1-(naphthalen-1- yl)ethyl)-3-(3-(trifluoromethyl) phenyl) propanamide achieved enantioseparation on 1-napthalene vancomycin chiral stationary phase using D-tartaric acid, diethyl L-tartrate and diethyl D-tartrate as chiral mobile phase additives. Conclusion: The chiral recognition in our experiment was based on the hydrogen-bonding, dipoledipole and π-π interactions among the solutes, chiral stationary phases and chiral mobile phase additives. In addition, the space adaptability of chiral stationary phases also affected the separation efficacy.

A simple and rapid method for chiral separation of amlodipine using dual chiral mobile phase additives

2014 ◽  
Vol 6 (12) ◽  
pp. 4408 ◽  
Author(s):  
Jiaqi Xie ◽  
Qi Tan ◽  
Lin Yang ◽  
Shenzhi Lai ◽  
Shaotan Tang ◽  
...  
Keyword(s):  
Rapid Method ◽  
Chiral Separation ◽  
Mobile Phase ◽  
Mobile Phase Additives ◽  
Chiral Mobile Phase Additives

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

2020 ◽  
Author(s):  
Pranav Pathak ◽  
Krishnapriya Mohanraj
Keyword(s):  
Mobile Phase ◽  
Cost Effective ◽  
Hplc Method ◽  
Enantiomeric Resolution ◽  
Factors Affecting ◽  
Mobile Phase Additives ◽  
Ich Guidelines ◽  
Chiral Mobile Phase Additive ◽  
Mobile Phase Additive ◽  
Chiral Mobile Phase Additives

<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>

Chiral stationary phases in concert with homologous chiral mobile phase additives: Push/pull model

Chirality ◽  
1993 ◽  
Vol 5 (4) ◽  
pp. 201-206 ◽  
Author(s):  
Keith J. Duff ◽  
Hannah L. Gray ◽  
Rachael J. Gray ◽  
Caroline C. Bahler
Keyword(s):  
Mobile Phase ◽  
Stationary Phases ◽  
Chiral Stationary Phases ◽  
Mobile Phase Additives ◽  
Chiral Mobile Phase Additives
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