The present study propounds an innovative diagnostic hybrid dual recognition strategy to detect trace amounts of pregabalin (PGB) using the combination of two powerful metal-organic framework (MOF) structures and the molecularly imprinted polymer (MIP) technique. To improve the analytical property of the electrode surface, copper-benzene-1,3,5-tricarboxylic acid frameworks (Cu-BTC MOFs) were directly synthesized on the glassy carbon electrode (GCE). Afterwards, MIP film was synthesized via the in situ dopamine (DA) electropolymerization method. To explore the effect of independent variables on the MIP construction, the Box-Behnken design was considered to determine the response surface methodology. In this sense, the predicted optimum combination variables were DA= 3 mM, pH = 7.4, cycle number = 16, KOH 4 mM, KOH: Et-OH ratio of 5:1 and 18 min elution time. Incubation time was obtained at 12 min. Electrochemical impedance spectroscopy (EIS) was used to determine the PGB analyte. The linear dynamic concentration range and limit of detection (LOD) were 0.05–800 pM and 2.9 fM, respectively. The imprinting calculated factor was 24.60, showing high interaction between the PGB and DA monomer. Inter-day and intra-day reproducibility measurements showed 2.08% and 1.58% and, 98% of the initial current response was maintained. Coefficients of selectivity against the PGB, for tapentadol, gabapentin, levetiracetam, L-Carnitine, and L-Histidine were 1, 5.52, 8.75, 2.8, 6.56 and 6.56 respectively. Cyclic voltammetry (CV) at various scan rates verified that adsorption kinetics follows a diffusion control mechanism. Finally, the efficiency of the GCE/Cu-BTC/ePDA-MIP sensor in real samples was evaluated and satisfactory results were achieved.
