<p> The development and comparison of two distinct analytical approaches is presented for quantifying clarithromycin in human plasma: a method based on ultra-performance liquid chromatography coupled with tandem mass spectrometry and a novel electrochemical immunosensor. The use of both techniques is justified by their ability to meet distinct operational requirements, ranging from high-throughput centralized analysis to rapid, point-of-care monitoring, which is essential for therapeutic drug monitoring and pharmacokinetic studies. The developed chromatographic method, which combines protein precipitation with subsequent liquid-liquid extraction using tert-butyl methyl ether, demonstrated robust and reproducible performance. Demonstrating excellent linearity and precision within the validated concentration range (0.1 to 4.0&#xa0;µg per milliliter), the method achieved a limit of detection as low as 0.03&#xa0;µg ml^-1. In parallel, an electrochemical immunosensor was developed using functionalized magnetic beads and screen-printed carbon electrodes. The biosensor demonstrated the same detection limit as the chromatographic method, a rapid analysis time of under 30&#xa0;min, and high selectivity even in complex biological matrices. By comparing these two platforms, the study highlights their complementary strengths: the robustness and regulatory alignment of liquid chromatography-mass spectrometry versus the portability, speed, and operational simplicity of the immunosensor. This dual approach offers a more flexible and context-specific strategy for clarithromycin monitoring, from centralized laboratory workflows to decentralized or point-of-care applications.</p> Graphical Abstract <p></p>