Electrochemical sensor for tricyclic antidepressants with low nanomolar detection limit: Quantitative Determination of Amitriptyline and Nortriptyline in blood.

Amitriptyline and its metabolite, Nortriptyline are commonly used tricyclic antidepressant (TCA) drugs that are electrochemically active. In this work, the performance characteristics of a plasticized PVC membrane-coated glassy carbon (GC) electrode are described for the voltammetric quantification of Amitriptyline and Nortriptyline in whole blood. The highly lipophilic Amitriptyline and Nortriptyline preferentially partition into the plasticized PVC membrane where the free drug is oxidized on the GC electrode. The concentrations of the drugs in the membrane are orders of magnitude larger than in the sample solution, resulting in superb limit of detection (LOD) of the membrane-coated voltammetric sensor: 3 nmol/L for Amitriptyline and 20 nmol/L for Nortriptyline. Conversely, hydrophilic components of the sample solution, e.g., proteins, the protein-bound fraction of the drugs, and electrochemically active small molecules are blocked from entering the membrane, which provides exceptional selectivity for the membrane-coated sensor and feasibility for the measurements of Amitriptyline in whole blood. In this work, the concentrations of Amitriptyline and Nortriptyline were determined in whole blood using the sensor and the results of our analysis were compared to the results of the standard HPLC-MS method. Based on our experience, the one-step voltammetric methods with the membrane-coated sensor may become a real alternative to the significantly more complex HPLC-MS analysis.