Novel sensors for detection of anti-asthma drugs in pharmaceutical formulations

Abstract

The development of an effective technique for detecting anti-asthma drugs with adverse effects in the human body at high dosages remains a serious challenge. For this purpose, herein, we report a novel electrochemical detection method based on nanocomposite modified glassy carbon electrode (GCE) nano-sensors. Cobalt ferrite (CoFe2O4), titanium oxide (TiO2) and zinc oxide (ZnO) nanoparticles (ZnONPs) were synthesized as well as their respective nanocomposites (CoFe2O4-MWCNTs-Lipase, TiO2-MWCNTs-IL, ZnONPs-MWCNTsCytochrome c and MWCNTs-Ionic liquid-L-lysine) were successfully prepared. Subsequently, their surface morphology, crystal structure, functional groups, thermal stability, surface area as well as pore size distribution of the synthesized nanoparticles and the nanocomposites aspects were analysed. The characterization analyses were undertaken using scanning electron microscopy (SEM), transmission electron microscopy (TEM), X-ray diffraction (XRD), Brunauer-Emmett Teller (BET) adsorption analyses, thermal gravimetric analysis (TGA) and Fourier-transform infrared spectroscopy (FTIR). In addition, electrochemical characterization of the fabricated electrodes were examined using electrochemical impedance spectroscopy (EIS) in order to ensure the material’s suitability in electro-catalytic sensing by investigating the electron transfer kinetics of the redox probe at the modified electrode-solution interface. The fabricated nanocomposite based sensors; ZnONPs-MWCNTs-Cyt c-GCE, CoFe2O4- MWCNTs-Lipase-GCE, MWCNTs-IL-L-lysine-GCE and TiO2-MWCNTs-IL-GCE were tested for electrochemical determination of theophylline, salbutamol, prednisolone and terbutaline, respectively, using cyclic voltammetry (CV) and differential pulse voltammetry (DPV). The effect of varying scan rates, pH of the supporting electrolyte and accumulation time on the peak potential position and peak-currents, were studied with each electrode, and the optimum working parameters were selected. The ZnONPs-MWCNTs-Cyt c-GCE, CoFe2O4-MWCNTs-Lipase-GCE, MWCNTs-IL-L-lysine-GCE and TiO2-MWCNTs-IL-GCE sensors were found to exhibit excellent electro-catalytic activity towards theophylline, salbutamol, prednisolone and terbutaline. The synergy between these nanocomposite materials increased the electrochemical activity, the electron transfer rate and the electrode surface area, leading to high peak-current response for the determination of each drug. ZnONPs-MWCNTs-Cyt c-GCE sensor presented acceptable long-term stability, good reproducibility and repeatability. The limit of detection (LOD = 0.0012 µM) obtained was much lower than most of the given literature studies. Similarly, the CoFe2O4-MWCNTs-Lipase nanocomposite modified GCE for salbutamol (SAL) exhibited excellent stability, reproducibility and sensitivity with lowest detection limit (0.0240 µM) and limit of quantification (LOQ) of 0.0120 µM, over the concentration range of 0.05- 3.9 µM. In addition, the MWCNTs-IL-L-lysine-GCE exhibited outstanding electro-catalytic activity including excellent reproducibility, with LOD and LOQ of 0.0214 μM and 0.3016 μM, respectively, for prednisolone (PDN) detection. Moreover, at optimized electrochemical experimental conditions, the electrochemical performance of the constructed TiO2-MWCNTs-IL-GCE sensor for determination of terbutaline (TBS) was also evaluated. Stability, reproducibility as well as the detection limits were determined. A wide linear range of 0.5 µM to 3.0 µM as well as LOD and LOQ of 0.0162 µM and 0.2140 µM, respectively, were obtained and the results were compared with similarly reported electrodes for terbutaline detection. The selectivity of each sensor was also evaluated in presence of common interferences. There was no significant interference on the electrochemical peak-current response and peak position of each target analyte. The practical applicability of each fabricated sensor was investigated by the DPV method with respect to the detection of the four drugs under study in commercial pharmaceutical samples. In all cases, the sensors showed good percentage recovery performance in real dosage samples. From the experimental results, it is evident that the fabricated nanocomposite based sensors are ultra-sensitive for selective detection of the investigated four drugs in pharmaceutical formulations and other sample matrices.