Role of Chromatograph-based Analytical Techniques in Quantification of Chiral Compounds: An Update

Abstract

Background: Chiral purity is a critical quality attribute of pharmaceutical materials as chiral compounds may have different pharmacological and toxicological properties with their enantiomer (or diastereomers for molecules with multiple chiral centers). Getting high quality drugs to the market quickly is essential for the survival of pharmaceutical companies and in drug research and development. It is important note that about 40% of all man-made synthetic drugs are chiral, 60% of all pharmaceuticals are chiral and 45% chiral drugs are sold as racemate. So, the objective of the current review is to discuss various chromatographic techniques used for the separation of chiral compounds. Methods: Various bibliographic databases of previously published peer-reviewed research papers were explored and systematic data has been culminated in terms of various chromatographic techniques used for chiral compounds’ separation. A comparison of different techniques as well as their advantages are also discussed. Results: A comprehensive review of 130 papers including both, research and review articles, was carried out to make the article readily understandable. The analytical techniques have been discussed in detail. Apart from chromatographic techniques, other techniques such as circular dichroism, nuclear magnetic resonance, UV-visible spectroscopy using cyclodextrin derivatives have also been highlighted with proper citation of references. Conclusion: The pharmaceutical industries need analytical methods to conclude enantiomeric concentration and obtain a drug with single stereo configuration. The sensitive techniques such as HPLC, GCMS and LCMS etc. are used for identification and quantification of limited quantities of single enantiomers, specifically in drug discovery and development.

Silylated-Acetylated Cyclodextrins as Chiral Sensors for the Enantiodiscrimination of Fluorinated Anesthetics

“…Thanks to their chirality, derivatized and native cyclodextrins can give rise to stereoselective recognition phenomena, which can be exploited in asymmetric syntheses [ 4 , 5 ] in order to design chromatographic separation systems [ 6 , 7 , 8 , 9 , 10 ] or as chiral solvating agents (CSAs) for nuclear magnetic resonance (NMR) spectroscopy [ 4 , 6 , 7 , 8 , 9 , 10 , 11 , 12 , 13 ].…”

Enantiomeric separation of ketoprofen using Frovatriptan as a chiral derivatizing reagent

“…A comprehensive understanding of the unique pharmacological profiles exhibited by enantiomers is essential for the development of safe and efficacious drugs [1]. In many instances, a drug compound can exist in multiple enantiomeric forms, each with distinct pharmacological properties encompassing variances in potency, effectiveness, toxicity, and metabolism [2,3]. The increasing focus on producing single enantiomers reflects the recognition of the potential advantages stemming from comprehending and harnessing the unique characteristics of enantiomers Article Related Abbreviations: CDR, chiral derivatizing reagent; DCC, dicyclohexyl carbodiimide; DCM, dichloromethane; FRV, Frovatriptan; KET, ketoprofen.…”

Quinine as a highly responsive chiral sensor for the 1H and 19F NMR enantiodiscrimination of N-trifluoroacetyl amino acids with free carboxyl functions

“…Chirality pervades pharmaceutical and biomedical areas [1][2][3][4] to such an extent that the detection and quantification of enantiomeric compounds constitute the focus of dedicated research areas, leading to the development of efficient, reliable and reproducible methods for enantiomer differentiation, among which chiral chromatography [5][6][7][8][9][10][11] and nuclear magnetic resonance (NMR) spectroscopy [12][13][14][15][16][17][18][19] emerge in terms of popularity. Both of them are grounded in the use of suitable chiral selectors able to make enantiomers distinguishable by transferring them into a diastereomeric environment.…”