Paper-based potentiometric sensing devices modified with chemically reduced graphene oxide (CRGO) for trace level determination of pholcodine (opiate derivative drug)

Abstract

Robust, reliable and cost-effective paper-based analytical device for potentiometric pholcodine (opiate derivative drug) ion sensing has been prepared and characterized. A printed pholcodinium (PHL)²⁺/5-nitrobarbiturate (NB)^- ion-association complex as a sensory material-based all-solid-state ion-selective electrode (ISE) on a chemically reduced graphene oxide (CRGO) solid-contact, and a printed all-solid-state Ag/AgCl reference electrode, has been combined on a hydrophobic paper substrate coated with fluorinated alkyl silane (CF₃(CF₂)₇CH₂CH₂SiCl₃, C^F ₁₀). The sensors revealed a potentiometric slope of 28.7 ± 0.3 mV dec^-1 (R ² = 0.9998) over a linear range starting from 2.0 × 10^-7 M to 1.0 × 10^-2 M and a detection limit of 0.04 μg mL^-1. The repeatability and stability of the pholcodine paper-based sensor was found to be 2.32%. The RSD% (n = 6) was found to be 2.67% when using five different paper-based sensors. The sensor revealed an excellent selectivity towards PHL over dextromethorphan, codeine, ephedrine, carbinoxamine, caffeine, ketamine, and K⁺, Na⁺ and Ca²⁺ ions. It showed a good recovery (94-104%) for the determination of PHL in different artificial serum samples. The presented paper-based analytical device was successfully introduced for PHL determination in different pharmaceutical formulations (i.e. syrups and suspensions) containing pholcodine. The current work can be considered as a promising possible analytical tool to obtain cost-effective and disposable paper-based potentiometric sensing devices. These devices can be potentially manufacturable at large scales in pharmaceutical, clinical and forensic applications for opiate drug assessment.

Fig. 1. A schematic representation of the fabrication of paper-based ISE.

Fig. 2. (a) The relationship between the conductivity and the number of print cycles of CRGO; effect of cycles of bending at different bending angles on (b) resistance and (c) EMF.

Fig. 3. Calibration plots of the presented PHL sensors: (a) paper/CRGO/PHL-ISE and (b) GC/PHL-ISE.

Fig. 4. Impedance spectra of (a) GC/PHL-ISE and (b) paper/CRGO/PHL-ISE.

Fig. 5. Current reversal chronopotentiometry for (a) GC/PHL-ISE and (b) paper/CRGO/PHL-ISE.

Fig. 6. Water-layer test for (a) GC/PHL-ISE and (b) paper/CRGO/PHL-ISE.