#chiral_chromatography

Episode 4: From Peak to Standard: Preparative Isolation of Chiral Impurities

“Turning an analytical separation into an isolated, characterised, defensible impurity standard” Why isolate a chiral impurity at all Analytical scientists ask for isolated chiral impurities when a chromatogram is no longer enough. The reasons are concrete: structural elucidation of an unknown peak, preparation of a reference standard, response-factor determination, qualification under ICH impurity expectations, forced-degradation …

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Episode 3: State of the Art: Selectors, SFC, Speed, and Sensible Automation

What modern chiral separation science can do now, and where the honest limits still lie The present technology landscape The most useful framing of the current landscape is that it is no longer sensible to ask, in the abstract, whether chiral HPLC or chiral SFC is “the best” approach. Modern laboratories operate with both, or …

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Episode 2: Developing a Chiral HPLC Method: A Structure-Led Workflow

From a structural diagnosis of the analyte to a defendable, robust, lifecycle-ready method Start with the molecule, not the column catalogue A credible chiral method does not begin with random column screening. It begins with a short structural diagnosis of the analyte and the likely impurity set. The pKa values indicate whether the analyte is …

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Episode 1: Why Chirality Still Matters: Stereochemistry as a Critical Quality Attribute

The pharmaceutical meaning of chirality, the real impurity space, and where chiral HPLC fits The pharmaceutical meaning of chirality Chirality matters in drug development for a simple reason. Biological systems are chiral, so the body does not experience two stereoisomers as the same molecule. FDA stated this explicitly in its landmark 1992 stereoisomer guidance, noting …

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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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