Recent Chiral Stationary Phase Advancements in HPLC Analysis

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This review of pharmaceutical analysis in the last three years includes three categories of chiral liquid chromatography stationary phases: saccharides, macrocyclic substances, and porous organic materials.

A new article in the Journal of Chromatography A offers a review of recent developments in chiral stationary phases (CSPs) for pharmaceutical analysis using high performance liquid chromatography (HPLC) (1). Various CSPs, the research team said, are being developed because chiral pharmaceutical separation and analysis rely on them, and so they must be tailored to fit this purpose.

The researchers, from the Chinese Academy of Sciences in Lanzhou, China and Northeastern University in Shenyang, China, reviewed three types of CSPs. One was saccharides, which include amylose, cellulose, chitosan, and cyclodextrin; another, macrocycles, including macrocyclic glycopeptides, pillararenes, and polyamides; and the third being porous organic materials which include covalent organic frameworks (COFs), metal-organic frameworks (MOFs), and porous organic cages (1).

Chirality in drugs is a challenge when the pharmaceutical industry is perpetually seeking more optically pure medications (1). Chiral medications differ in pharmacodynamics, pharmacokinetics, and toxicity, but these authors say that often only one of the two mirror-image enantiomers has a therapeutic effect; the other may even cause side effects. In general, the researchers said, CSPs used in conjunction with HPLC can separate more than 90% of compounds that would be considered optically active.

The research team looked mainly at direct, rather than indirect, methods of HPLC separation of chiral substances. These included the macrocyclic compounds and porous organic frameworks. The direct method is viewed by the authors to be preferred because of its simplicity and convenience, although while commercial CSPs are widely available, they can be expensive (1). What’s more, even with their advantages these CSPs are considered to have limited separation ability, so more efficient, accurate, and economical choices are always being sought.


One objective the researchers had in publishing this study was to draw attention to the lack of reports, up to now, of real samples in previous studies. They said this reflects the current state of poor selectivity of CSPs, with both high selectivity and column capacity of stationary phases (SPs) in general being important in their estimation (1).

In summarizing the three CSP categories they evaluated, the authors began with saccharide-based CSPs, which they said were the first kind of material to be developed, and as a result there are many chiral columns derivative of saccharides in the commercial market (1). Similar to the saccharide cyclodextrin, macrocycles have a cavity structure and many active and easily modifiable sites on their surface. While porous organic frameworks are gaining traction, comparatively few instances currently exist of the likes of COFs and MOFs being used in actual chiral drug separation applications.

Suggestions for further research from the authors included more investigation into the chiral separation process itself, namely interactions between analytes and CSPs. And because pharmacological molecule structures are so typically complicated, they said, more or better calculations or measurements are needed to produce a thorough evaluation.


(1) Liu, H.; Wu, Z.; Chen, J.; Wang, J.; Qiu, H. Recent Advances in Chiral Liquid Chromatography Stationary Phases for Pharmaceutical Analysis. J. Chromatogr. A 2023, 1708, 464367. DOI: 10.1016/j.chroma.2023.464367