Simultaneous in-situ extraction and electrochemical detection of antidepressant drug imipramine and its active metabolite in human biofluid samples

The rapidly advancing modern healthcare system necessitates the development of cutting-edge technologies for therapeutic drug monitoring. Protein-bound drugs challenge the rapid quantification of analytical methods that require additional separation and cleanup processes, which delay the development of point-of-care testing platform. Here, a human serum albumin (HSA)/iron molybdate (FeM;Fe2(MoO4)3)/reduced graphene oxide (rGO) is reported for the in-situ extraction and determination of imipramine (IMP) drug and its active metabolite desipramine (DMP) in human serum and plasma samples. HSA was used for the extraction of drugs from the complex plasma proteins, and the extracted drugs were directly detected by FeM/rGO without additional sample cleanup. The developed sensor, which was optimized for the drug therapeutic window under normal conditions, exhibited a linear range of 10–756 ng/mL as well as a remarkable limit of detection and sensitivity of approximately 4 ± 2 ng/mL and 0.0124 ± 0.0003 µA cm−2 ng−1 mL, respectively, for IMP-DMP. The spike-and-recovery method was used to validate the developed sensor in real sample analysis. Based on the results, the sensing mechanism was elucidated: protein-protein interaction facilitates drug transportation from the plasma protein to electrode surface. Thereby, the HSA-FeM/rGO modified electrode recovered more drugs in biofluids compared with HSA unmodified electrode.