#chiral_chromatography

Part 7: Analytical Techniques for Stereochemistry

“Measuring handedness – tools and techniques that bring chirality into focus” Introduction Ensuring the correct stereochemistry and measuring stereochemical purity is a crucial aspect of pharmaceutical quality control and research. This part covers the major analytical techniques used to distinguish and quantify enantiomers and diastereomers in drug substances and products. Key techniques include: We’ll discuss …

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Harnessing JMP’s Prediction Profiler for Multi-Response Optimization of HPLC Method in Chiral Drug Separation

Synopsis The development of chromatographic methods for the separation of chiral drugs presents a significant challenge, necessitating a comprehensive understanding of the compounds’ chemical properties and the factors influencing their separation. This task is further complicated by the presence of process-related impurities that can disrupt the separation process and compromise the quality of the results. …

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Protein-based CSPs

Lead Proteins are complex, high-MW biopolymers composed of L-amino acids and possess ordered 3D-structure. They are known to bind /interact  stereoselectively with small molecules  reversibly, making them extremely versatile CSPs for chiral separation of drug molecules.   Number of CSPs has been developed by immobilizing proteins. These type of CSPs operate under RP-mode; (phosphate buffer …

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Donor-Acceptor (Pirkle)-type CSPs

Lead William H Pirkle developed these CSPs and are  based on the ionic or covalent attachment of one enantiomer of an amino acid derivative to aminopropyl silica. Pirkle phases contain π-electron donor or acceptor rings substituted with H-bonding moieties. Donor–acceptor-type CSPs capitalize on synthetic or semi-synthetic chiral low-molecular-weight chiral selectors capable of recognizing chiral analytes …

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Cyclodextrin-based CSPs

Lead Cyclodextrin-based CSP belongs to the cavity type. Armstrong is considered the father of cyclodextrin-based CSPs. CDs are employed in various fields of analytical chemistry, due to their tendency to form reversible inclusion complexes and recognize chiral analytes. CDs are a type of macrocyclic D-(+)-glucopyranose oligomers linked by α-1,4-glycosidic linkages, as seen in Figure, under chemistry . …

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Polysaccharide-based CSPs

  Lead Surprisingly, chiral chromatography could not be performed in 1980 because there was no single chiral stationary phase on the market. But as the 1980s came to a close, chiral chromatography began to get more and more attention, thanks in large part to the efforts of Okamoto’s institute in Japan, Pirkle and Armstrong’s teams …

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Chiral selectors

Lead A wide range of chiral compounds have been examined as chiral selectors with regard to their ability to separate enantiomers using chromatography as part of the development of CSPs. From low-molecular-weight chemicals to polymers with both synthetic and biological origins, the chiral molecules investigated as potential CSs span almost the full spectrum of chemical …

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Direct chiral HPLC separation on CSPs

Chiral stationary phases (CSPs) The most convenient and most popular analytical methodology to assess chiral purity is the direct separation of enantiomers on so-called chiral stationary phases (CSPs). CSPs consists of an (ideally) inert chromatographic support ( usually silica micro-particles) on to which the chiral selector (CS; single enantiomer of a chiral molecule) is physically …

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Chiral HPLC separation: strategy and approaches

Strategy The basic aspect is to provide the right chiral environment where by the enantiomeric pair become distinguishable. In HPLC how do we construct the chiral environment? To understand this let us look at the variables available, in the HPLC system, that can be exploited for this purpose. The following is a schematic diagram of …

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Chiral chromatography

What is chiral chromatography? Chiral chromatography is now widely understood and applied in daily life. The correct phrase, however, is “enantioselective chromatography”. Chiral chromatography has developed into the most popular method for enantiomeric purity assessment and pure enantiomer separation, both on an analytical and preparative scale. The initial step in any investigation into enantioselective synthesis …

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