Molecular Imprinted Polymer Based Impedimetric Sensor for Trace Level Determination of Digoxin in Biological and Pharmaceutical Samples

Background: Molecularly Imprinted Polymers (MIPs) are used as artificial receptors in biosensors for the detection of a wide range of analytes from small drug molecules to large molecular weight biomolecules. Quantification of Digoxin (DIG) in human serum and pharmaceutical samples has very high importance due to its low margin of safety. In this report, a highly sensitive molecularly imprinted polymer for DIG is prepared and the detection of analyte was conducted using electrochemical impedance spectroscopy. Methods: Bulk polymerization method was chosen for the preparation of MIP because of its better preservation of the pockets formed during the polymerization. DIG imprinted polymer was prepared by thermal polymerization of Methacrylic Acid (MAA) cross-linked with Ethyleneglycol Dimethacrylate (EGDMA) in the presence of DIG. The molecular interactions via hydrogen bonding between template and monomer in MIP and Non-Imprinted Polymer (NIP) were confirmed using Fourier Transform Infrared (FTIR) spectroscopy. Morphological studies were performed before and after extraction of the template using Scanning Electron Microscopy (SEM). MIP modified carbon paste electrode (MIPCPE) was fabricated by mixing optimized quantities of graphite, the polymer, and eicosane. The change in charge transfer Resistance (Rct) at the electrode-electrolyte (MIPCPE-electrolyte) interface before and after addition of DIG solution was studied using electrochemical impedimetric sensing of DIG. Results: The surface morphology of the MIPCPE shows better porosity in comparison to non-imprinted polymer CPE (NIPCPE) and MIPCPE before extraction of the template. In contrast to NIPCE, the fabricated MIPCPE shows a significant increase in Rct after addition of DIG. The MIPCPE based impedimetric sensor is able to detect DIG over a wide range of concentration from 1.0 × 10-9 M to 0.5 × 10-7 M with a detection limit 6.95 × 10-11 M. The selectivity coefficients obtained for the MIPCPE and NIPCPE reveal specific recognition MIPCPE sensor towards DIG. The recovery rates of DIG from the spiked blood serum and pharmaceutical samples are in the range of sensor 89-101%. Conclusion: In the present work, the capability of MIPs as molecular recognition elements is proved by reporting a selective and sensitive impedimetric sensor for DIG. The selectivity coefficients (K) of MIPCPE and NIPCPE obtained for the DIG and interferents show better selectivity of the sensor towards DIG in the presence of interferents. The proposed sensor also shows satisfactory stability, reproducibility, and repeatability for DIG. The proposed sensor was successfully applied for the quantitative estimation of DIG in serum and pharmaceutical samples with appreciable recoveries. Keywords: Digoxin, molecularly imprinted polymer, free-radical polymerization, scanning electron microscope, electrochemical impedance spectroscopy, Carbon paste electrode.