Theoretical models in LC based bioanalytical method development.

Bioanalytical method development largely depends on the experience and the preference of the developer. Mathematical models could help in selecting the proper conditions to develop a selective and robust method, using liquid chromatography, liquid-liquid extraction, solid phase extraction and protein precipitation. This paper reviews the literature providing relevant equations and algorithms to model LC based bioanalytical methods for the quantification of small molecules. By using the cited references, it will be possible to build models to describe the analytical methods either as an approximate impression or in a detailed way, incorporating many experimental variables. Special attention has been paid to matrix effects, the most important issues in bioanalysis and possible solutions to handle these issues are discussed. By proper use of the proposed models a more structured method development is accomplished, resulting in a description of the method that could be used for future use to control the complete bioanalytical method.