Electrochemical Detection of Benzodiazepines, Following Liquid Chromatography, for Applications in Pharmaceutical, Biomedical and Forensic Investigations

Kevin C Honeychurch,John P Hart

doi:10.5640/insc.040101

Abstract

Benzodiazepines are an important class of drugs commonly administered with a potential for abuse and environmental pollution. This review focuses on the liquid chromatographic electrochemical detection of the benzodiazepine class of drugs. These are characterised by a readily electrochemically reducible azomethine group, with a number also substituted by other electrochemically active groups. Liquid chromatography employing both single and dual electrode detection has been reported for a variety of benzodiazepines and their metabolites in biological, pharmaceutical, biomedical and forensic investigations. Recently, electrochemistry has been utilised to mimic biological oxidation processes and has been combined with liquid chromatography/mass spectroscopy for their identification and quantification of the products generated. The present review focuses on recent developments in liquid chromatographic- electrochemical determination of benzodiazepines reported since 2006, with earlier reports given in summary.

Highlights

Since the discovery in 1955 of the first benzodiazepine drug, chlordiazepoxide hydrochloride (Librium®) [1], a number of structurally similar benzodiazepines have been synthesised, with about thirty presently in medical use [2]
The diazepine ring system B is required for optimum receptor binding; the amide or N-alkyl groups contribute to receptor binding, with biological activity increased by the addition of a methyl group at the 1-position, larger groups, such as tert-butyl result in decrease activity [6]
This review focuses on liquid chromatography coupled with electrochemically based techniques for the determination of the benzodiazepine class of drugs

Summary

Introduction

Since the discovery in 1955 of the first benzodiazepine drug, chlordiazepoxide hydrochloride (Librium®) [1], a number of structurally similar benzodiazepines have been synthesised, with about thirty presently in medical use [2] These are utilised widely as tranquillisers, hypnotics, sedatives, antidepressants, for both humans [2,3,4] and animals [5], which act by increasing the efficiency of the neurotransmitter γ-aminobutyric acid (GABA) to decrease the communication between neurons, so calming many of the functions of the brain [2,3]. Reviews [9,10] have highlighted other issues, especially with the elderly, with increased reports of falls and a resulting increased incidence of hip fractures and risk of cerebrovascular events and deaths Due to their wide pharmaceutical applications, and subsequent disposal, concern has arisen regarding other areas effecting the wider population.

The Electrochemical Behaviour of Benzodiazepines

Liquid Chromatography Electrochemical Detection of Benzodiazepines

Applications

Findings

Conclusion