In recent years, biotechnologically-derived drugs have been a major focus of research and development in the pharmaceutical industry. Their pharmacokinetics and pharmacokinetic/pharmacodynamic relationships impact every stage of the development process and require their assessment in the circulation in preclinical species and in humans. To this end, immunoassays are a reference, but standardisation remains an issue owing to the restricted pattern of antibody specificity and interference with endogenous components. As an alternative, we report here analytical strategies involving liquid chromatography coupled to mass spectrometry (LC-MS) for the accurate quantification of therapeutic proteins and antibodies in biological fluids.