The present work focuses on the development of a label-free and ultrasensitive immunoassay for the detection of the drug amitriptyline in human serum. Reflectometric interference spectroscopy is used as the detection method, providing a simple, but highly sensitive optical setup. Amitriptyline is a common antidepressant; however, it has a small therapeutic window and can cause severe side effects in case of wrong dosage. Therefore, it is highly recommended for therapeutic drug monitoring to control the drug level. The limit of detection for this optical immunosensor was determined in buffer (0.3 μg/L) and in human serum (0.5 μg/L). It has become evident that this assay can compete with HPLC measurements. For drug concentrations at a normal level or above, the sample can be diluted up to 1:100. Especially for limited sample volumes, this is a great advantage. The sensor surface shows very high stability, and together with the regeneration solution 80 measurement cycles can be performed on each transducer chip. Cross-reactivity experiments indicate that a sum determination of several tricyclic antidepressants is possible.

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