Advances and challenges in the pharmacokinetics and bioanalysis of chiral drugs

Abstract Enantioselective analytical approaches are essential for monitoring pharmacokinetics and acquiring accurate data to better understand the role of stereochemistry in pharmacokinetics. Enantioselectivity significantly impacts the pharmacokinetics of chiral drugs, especially in metabolic profile, leading to toxicity of enantiomer. Consequently, there is a need to study the pharmacokinetics of enantiomerically pure drugs and racemates as they differ in affinity with enzymes and proteins. Combining the best enantioseparation conditions with the specified biological matrix and the intended purpose of the analysis is a challenging task. This review discusses the importance of chirality in stereoselective pharmacokinetics with more relevant examples, various enantioselective analytical techniques, and stationary phases employed. Challenges such as lack of universal chiral columns, biological inversion of the isomers, and others have been discussed. Further presented the recent advances in the screening of chiral drugs and innovative improvements in the analytical approaches for chiral molecule analysis such as supercritical fluid chromatography, simulated moving bed chromatography, and other techniques are discussed.