Advances in Chiral Separation Techniques for Calcium Channel Blockers: Analytical Strategies and Future Perspectives in Antihypertensive Drug Development (2015–2025)

ABSTRACT

Chirality plays a crucial role in pharmaceutical development, as enantiomers often display distinct therapeutic, pharmacokinetic, and safety profiles. Calcium channel blockers (CCBs), a cornerstone in antihypertensive therapy, frequently possess one or more chiral centers, making enantioselective analysis essential for pharmacological and regulatory accuracy. Despite growing evidence of stereoselective differences, most marketed CCBs remain available as racemates, underscoring the need for refined analytical approaches. This review aims to bridge that gap by critically synthesizing advances in analytical, bioanalytical, and regulatory strategies for chiral CCBs. Key separation platforms—including high‐performance liquid chromatography (HPLC), capillary electrophoresis (

), gas chromatography (GC), and supercritical fluid chromatography (SFC)—are evaluated with emphasis on chiral stationary phases such as polysaccharides, cyclodextrins, macrocyclic antibiotics, and crown ethers. Recent innovations in hyphenated mass spectrometry, spectroscopic techniques, and eco‐friendly miniaturized systems are highlighted for their ability to enhance enantioselectivity, reduce solvent consumption, and improve sensitivity in complex matrices. Case studies illustrate the pharmacokinetic and pharmacodynamic relevance of individual enantiomers, reinforcing the clinical impact of chirality in CCB therapy. The review concludes by identifying current limitations and exploring future directions, including AI‐assisted selector design, green chemistry integration, and lab‐on‐chip platforms to advance personalized antihypertensive treatment.