Application and Challenges of LC-MS for Bioanalysis

High performance liquid chromatography coupled with mass spectrometry has become a pervasive analytical technique in the pharmaceutical industry, especially for bioanalysis because the combination of LC with MS adds an orthogonal detection dimension, which provides extraordinary sensitivity, selectivity, and high throughput. However, the technique often suffers from matrix effects, especially when using ESI for analyzing extracts of complicated biological matrices. Matrix effects can be observed either as a loss in response (ion suppression) or as an increase in response (ion enhancement). Both the ion suppression and enhancement dramatically affect performance of bioanalytical methods. That is why FDA’s guidance requires that matrix effects be evaluated to fully validate a bioanalytical method for clinical and pre-clinical studies. The symposium focuses on the advancement of the LC-MS technique for bioanalysis, the causes of matrix effects, and the methods to evaluate and minimize them. A novel concept, Matrix Effect Factor (MEF) using stable isotopically labeled internal standards will be introduced and its application will be discussed.