Abstract
The interaction between proteins and drugs or other bioactive compounds has been widely explored over the past years. Several methods for analysis of this phenomenon have been developed and improved. Nowadays, increasing attention is paid to innovative methods, such as high performance affinity liquid chromatography (HPALC) and affinity capillary electrophoresis (ACE), taking into account various advantages. Moreover, the development of separation methods for the analysis and resolution of chiral drugs has been an area of ongoing interest in analytical and medicinal chemistry research. In addition to bioaffinity binding studies, both HPALC and ACE al-low one to perform other type of analyses, namely, displacement studies and enantioseparation of racemic or enantiomeric mixtures. Actually, proteins used as chiral selectors in chromatographic and electrophoretic methods have unique enantioselective properties demonstrating suitability for the enantioseparation of a large variety of chiral drugs or other bioactive compounds. This review is mainly focused in chromatographic and electrophoretic methods using human serum albumin (HSA), the most abundant plasma protein, as chiral selector for binding affinity analysis and enantioresolution of drugs. For both analytical purposes, updated examples are presented to highlight recent applications and current trends.
Highlights
Plasma proteins are capable of interacting with about 43% of the 1500 drugs most commonly used in clinical practice [1,2]
The results showed that the binding of imazalil to human serum albumin (HSA) was enantioselective which provided the first evidence of enantioselective toxicokinetic data for this compound [153]
The importance of plasma protein binding in drug discovery and development is unquestionable and several studies have been described over the years
Summary
Plasma proteins are capable of interacting with about 43% of the 1500 drugs most commonly used in clinical practice [1,2]. Studies of the interaction of chiral drugs with plasma proteins can provide valuable information for understanding the differences that are observed between a pair of enantiomers They can help to predict the behavior of a chiral compound in the human body, to understand whether there are interactions between drugs and between the enantiomers of a compound and, above all, to help in determining the appropriate therapeutic doses [1,2,50]. These are some of the reasons that justify why a drug is only approved for marketing after various studies have been carried out, which include plasma protein binding affinity. The current trends and perspectives in the field of HSA binding affinity are evidenced by considering updated examples of both chromatographic and electrophoretic methods
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