Psychoactive Substances and How to Find Them: Electrochemiluminescence As a Strategy for Identification and Differentiation of Drug Species
Authors: Brown Kelly , Allan Pamela , Francis Paul , Dennany Lynn 
Published: December 2020

Rapid and continuous appearance of novel psychoactive substances (NPS) onto the global drug market has highlighted the significant requirement for new and alternative screening methodologies. Current screening protocols, primarily consisting of the colorimetric NIK® tests, are not only inadequate for NPS but they are not compatible with any matrix other than the pure drug product.
Here we discuss the potential power of electrochemiluminescence (ECL) as a simple tool for drug screening. The intrinsic advantages of ECL make it an ideal candidate as an alternative analytical technique for the rapid identification of drug species, within a range of complex matrices. NPS, often contain a mixture of substances, while analysis of complex matrices can be challenging due to a number of potential interfering species present. Traditional ECL systems typically employ a single ruthenium based luminophore. This single complex approach often prevents the successful differentiation of structurally similar compounds, which typically interact with the complex via analogous mechanisms producing emission within the same potential regions. Multiplexed sensors utilising several different metal luminophores as well as pH controlled emission offer viable mechanisms to tackle the limited specificity associated with ECL techniques.
Utilising tropane alkaloids, atropine and scopolamine as model compounds, a straightforward ECL sensor based upon a portable screen printed electrode set up, offering rapid results at minimal cost in a variety of complex matrices has been developed. The sensors portability matches that of current screening protocols but utilises less hazardous materials and removed subjectivity. Two alternative methodologies to improve the specificity offered by ECL were investigated within this study.
By exploiting the relationship between pH and ECL emission the ability to differentiate between the two structurally similar species, upon a simple ruthenium based sensor, such as shown in Figure 1, is possible. The use of pH controlled ECL, allows for emission from one species to be “switched off” within a mixed sample. With knowledge of the target species pKa this methodology can be used to tailor the sensor toward a variety of species, offering improved specificity without having to alter sensor fabrication.
The employment of different metal luminophores, such as iridium and osmium, can offer the possibility to increase specificity, with different selectivity offered by each luminophore. By using a combination of different metal luminophores the ability to differentiate between structurally similar species becomes possible, something currently not attainable when utilising a single luminophore system. Furthermore, the opportunity to negate previously encountered interference effects due to matrix composition becomes viable. By utilising a combination of different metal complexes we have successfully demonstrated the ability to effectively negate the interference effect from naturally occurring amino acids present in biological matrices such as human serum, a previously noted limitation for the use of ECL within biological matrices.
Here we provide a strong proof-of-concept for the development of multiplexed ECL sensors, utilising several luminophores to tackle the limited specificity currently offered by ECL. By tackling this limitation, the potential applications of current ECL based sensors could be expanded significantly. Whats more our sensor design offers the ability to analyse a variety of complex biological matrices without the requirement of sample preparation. The potential to utilise one portable technique for drug screening across a variety of matrices, with the ability to tailor emission toward a specific drug species, without the requirement of a full lab facility will not only benefit the wider sensing community but such sensors offer the potential to reduce cost, increase throughput and simplify drug screening procedures in a variety of fields. Finally, a key challenge of electroanalytical sensors is multiplexed detection and this study will facilitate understanding of ECL based sensors to overcome this hurdle.

Figure 1