Electrochemical Discrimination of Salbutamol from Its Excipients in Ventolin(TM) at Nanoporous Gold Microdisc Arrays

The emergence of specific drug–device combination products in the inhalable pharmaceutical industry demands more sophistication of device functionality in the form of an embedded sensing platform to increase patient safety and extend patent coverage. Controlling the nebuliser function at a miniaturised, integrated electrochemical sensing platform with rapid response time and supporting novel algorithms could deliver such a technology offering. Development of a nanoporous gold (NPG) electrochemical sensor capable of creating a unique fingerprint signal generated by inhalable pharmaceuticals provided the impetus for our study of the electrooxidation of salbutamol, which is the active bronchodilatory ingredient in Ventolin(TM) formulations. It was demonstrated that, at NPG-modified microdisc electrode arrays, salbutamol is distinguishable from the chloride excipient present at 0.0154 M using linear sweep voltammetry and can be detected amperometrically. In contrast, bare gold microdisc electrode arrays cannot afford such discrimination, as the potential for salbutamol oxidation and chloride adsorption reactions overlap. The discriminative power of NPG originates from the nanoconfinement effect for chloride in the internal pores of NPG, which selectively enhances the electron transfer kinetics of this more sluggish reaction relative to that of the faster, diffusion-controlled salbutamol oxidation. Sensing was performed at a fully integrated three-electrode cell-on-chip using Pt as a quasi-reference electrode.