Strategies for improving the quantitative bioanalytical performance of LC-MS in pharmacokinetic studies

Quantitative bioanalysis is urgently required for the evaluation of pharmacokinetic properties of a drug and to demonstrate the body exposure to the parent drug and/or metabolite for interpretation of the efficacy and toxicity. New trends in drug discovery and development will be always posing challenges on LC-MS-based quantitative bioanalysis. The focus of this minireview is to highlight the commonly used strategies for improving the quantitative bioanalytical performance including overcoming matrix effects and improving MS detectability. "LC-electrolyte effects" and "pulse gradient chromatography" proposed by our group are new approaches that have also showed potential efficiencies on improving overall bioassay performance, including lowering lower limit of quantification (LLOQ), enlarging upper limit of quantification (ULOQ), decreasing matrix effects, and overcoming elutropic effects, etc.. They should also work well in metabolic profiling studies and other important analytical fields, such as food pesticide residue analysis, environmental analysis, clinical and forensic toxicology, doping control, and so on.