This article is the first of four on the bioanalysis of small-molecule drugs and metabolites by liquid chromatography–mass spectrometry (LC–MS). In this article, we provide an overview of the fundamentals, workflow, regulations, and modern trends on these quantitative assays.

Bioanalysis is the term used to describe the quantitative assessment of drugs and their metabolites in biological fluids (such as blood, plasma, and urine) and tissue homogenates. Bioanalysis plays a pivotal role in the research, discovery, development, and commercialization of new drug therapeutics, and also offers many career opportunities for analytical chemists. Initially, bioanalysis was first used to detect illicit drugs in biological fluids to investigate overdosing in forensic cases. The field then grew from there with the development of pharmacokinetic science (1).