Leveraging Advances inHPLCand Sample Preparation to MaximizeDMPKData Quality

Abstract

High throughput bioanalytical methods are essential to support the rapid discovery and development of drugs in the pharmaceutical industry. Liquid chromatography coupled with tandem mass spectrometric detection (LC‐MS/MS) is considered the benchmark analytical methodology to be employed for the quantification of new chemical entities in biological fluids. Because of the high sensitivity and selectivity of LC‐MS/MS, the time required for method development and subsequent sample analysis is dramatically reduced. Rigorous chromatographic resolutions of analytes and/or tedious sample extraction protocols are typically not required even when complex biological matrices are used. Nevertheless, effective sample preparation and appropriate chromatographic separation of endogenous matrix components is required to ensure the quality of the data. The importance of sample preparation stems from three major concerns: removing interferences from the biological sample matrices, concentrating analyte(s) of interest, and improving analytical system performance. The choice of sample preparation method should be dependent on the quality of the data required.