LC enantioseparation of active pharmaceutical ingredients using rationally synthesized CDRs and chiral molecules with high molar absorptivity

The synthesis of optically active compounds requires determination of ee, er, and enantiomeric purity. The aim of the present paper is to review the synthesis of several chiral derivatizing reagents (CDRs) in a rational manner, which were successful for the separation and isolation of enantiomers of a variety of active pharmaceutical ingredients and other important and useful racemates. Besides, the application of (i) certain enantiomerically pure amines, either directly or by incorporating each of them as chiral auxiliary in difluorodinitrobenzene or cyanuric chloride moieties to construct the CDR, (ii) (S)-ketoprofen and (S)-levofloxacin as chiral platforms, and (iii) a few isothiocyanates, have been suitably included. Attention is drawn to the use of water micellar mobile phase as the "green" RP-HPLC method and the use of simple achiral derivatization with ninhydrin, particularly. Synthesis of CDRs and their application for enantioseparation of racemates and detagging of certain chromophoric reagent components for obtaining native enantiomers are other interesting features included herein. The methods can be easily used to determine and control enantiomeric purity with advantages over a variety of commercial chiral phases. This comprehensive review not only highlights innovative methodologies for enantioseparation but also underscores their practical applications in controlling and ensuring the enantiomeric purity of pharmaceutical compounds.