Voltammetric Electronic Tongue for the Simultaneous Determination of Three Benzodiazepines.

Anna Herrera-Chacón,Manel Del Valle,Andreu González-Calabuig,Farnoush Faridbod,Farzad Torabi,Jahan B Ghasemi

doi:10.3390/s19225002

Anna Herrera-Chacón, Manel Del Valle + Show 4 more

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https://doi.org/10.3390/s19225002

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Abstract

The presented manuscript reports the simultaneous detection of a ternary mixture of the benzodiazepines diazepam, lorazepam, and flunitrazepam using an array of voltammetric sensors and the electronic tongue principle. The electrodes used in the array were selected from a set of differently modified graphite epoxy composite electrodes; specifically, six electrodes were used incorporating metallic nanoparticles of Cu and Pt, oxide nanoparticles of CuO and WO3, plus pristine electrodes of epoxy-graphite and metallic Pt disk. Cyclic voltammetry was the technique used to obtain the voltammetric responses. Multivariate examination using Principal Component Analysis (PCA) justified the choice of sensors in order to get the proper discrimination of the benzodiazepines. Next, a quantitative model to predict the concentrations of mixtures of the three benzodiazepines was built employing the set of voltammograms, and was first processed with the Discrete Wavelet Transform, which fed an artificial neural network response model. The developed model successfully predicted the concentration of the three compounds with a normalized root mean square error (NRMSE) of 0.034 and 0.106 for the training and test subsets, respectively, and coefficient of correlation R ≥ 0.938 in the predicted vs. expected concentrations comparison graph.

Highlights

Benzodiazepines (BZs) are a family of drugs massively used worldwide since the 1960s, when they were first introduced
The electrochemical behavior has been explained by the 2e−, 2H+ reduction of the 4,5-azomethine group at the ring to give the corresponding dihydro species, plus extra reduction of present active moieties, e.g., the nitro group in the case of flunitrazepam
The proposed approach reports the use of a voltammetric sensor array that has been developed and validated as a rapid, reliable, and accurate method for simultaneous determination of ternary mixtures of BZs products diazepam, flunitrazepam, and lorazepam

Summary

Introduction

Benzodiazepines (BZs) are a family of drugs massively used worldwide since the 1960s, when they were first introduced. BZs are frequently prescribed as anxiolytics, anticonvulsants, muscle relaxants, and as treatment for alcohol and drug abuse [1]. They are used in clinical anesthesia due to their sedative and relaxant properties in a variety of procedures. BZs enhance GABAA receptor affinity producing sedative, tranquilizing, and sleep-inducing effects. BZs supposedly present low toxicity when administered at clinical doses but may be potentially dangerous when used at high doses. Even though they are well-known drugs, they are difficult to identify in the body after their use. The identification of BZs in blood [3], urine [4], hair samples [5], or in post-mortem studies may be interesting in terms of criminology and forensic studies [6]

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