Roles of LC‐MS Bioanalysis in Drug Discovery, Development, and Therapeutic Drug Monitoring

In liquid chromatography—mass spectrometry (LC-MS) bioanalysis, assay selectivity can be readily achieved by three stages of separation of the analyte(s) of interest from unwanted components in the biological matrix: (i) sample extraction (protein precipitation, liquid—liquid extraction, solid-phase extraction, etc.), (ii) column chromatography, and (iii) tandem mass spectrometric detection in selected reaction monitoring (SRM) or multiple reaction monitoring (MRM) mode. The focus of LC-MS bioanalysis in the pharmaceutical industry is to provide quantitative measurement of the active drug and/or its metabolite(s) for the accurate assessment of pharmacokinetics (PK), toxicokinetics (TK), bioavailability (BA), bioequivalence (BE), and exposure-response (pharmacokinetics/ pharmacodynamics) relationships. LC-MS bioanalysis has become a primary tool in every stage of drug discovery, preclinical and clinical drug development, and post-approval therapeutic drug monitoring (TDM). In additional to its traditional roles in various studies for small molecule drugs and their metabolites, LC-MS is increasingly being used to assay biomarkers in proof-of-concept studies and biopharmaceuticals such as proteins.