From Chiral Drugs to Chiral Metabolites: The NMR Approach
Pp. 182-215 (34)
Gloria Uccello-Barretta, Federica Balzano, Federica Aiello and Roberta Settambolo
Quantification and identification of chiral drugs and their metabolites
constitutes a significant issue for both the pharmaceutical industry and the regulatory
authorities, which led to a continuous growth of research areas devoted to the
development of direct methods of discrimination of enantiomers. Stereoisomers
frequently differ in terms of their biological activity and pharmacokinetic profiles as
well as their metabolites can be toxic or pharmacologically active, just like drug
candidates. NMR spectroscopy provides several tools in the field of the identification
and quantification of chiral compounds, based on the use of suitable chiral auxiliaries
which have the role of converting enantiomeric mixtures into their diastereoisomeric
derivatives or solvates, the NMR resonances of which are distinguishable in principle.
The survey will be addressed on the NMR determinations of the enantiomeric purity of
chiral compounds, with an outline of the three classes of chiral auxiliaries for NMR,
without any intent of giving an exhaustive analysis of literature data. Particular attention
will be focused on the literature regarding the use of NMR spectroscopy for the
identification and quantification of chiral drugs and metabolites.
Chiral, drugs, metabolites, NMR.
Dipartimento di Chimica e Chimica Industriale, Università di Pisa, via Risorgimento 35, 56126 Pisa, Italy.