Abstract
Drug-drug interactions (DDI) are a critical concern in drug development and clinical practice. A new molecular entity often requires numerous clinical DDI studies to assess potential risks in humans, which involves significant time, cost, and risk to healthy study participants. Consequently, there is growing interest in innovative techniques to improve the prediction of transporter-mediated DDI. Researchers in this field have focused on identifying endogenous molecules as biomarkers of transporter function. The development of biomarkers is notably more complex than that of exogenous drugs. Owing to their inherent selectivity, sensitivity, and ability to provide absolute quantification, liquid chromatography-mass spectrometry (LC-MS) and liquid chromatography-tandem mass spectrometry (LC-MS/MS) are increasingly being employed for the quantitative investigation of new biomarkers. This review article presents recently developed bioanalytical approaches using LC-MS/MS for putative transporter biomarkers identified to date. Additionally, we summarize the published baseline endogenous levels of these potential biomarkers in a biological matrix to suggest a set of reference values for future research, thereby minimizing errors in biomarker-related data analyses or calculations.