Detection and semi-quantitative determination of designer benzodiazepines in serum using LC-MSn

Benzodiazepines play an important role in forensic toxicology as they are widely prescribed in the treatment of psychiatric disorders and also used as drugs of abuse. In 2012 the group of New Psychoactive Substances (NPS) including numerous synthetic cannabinoids and designer stimulants (“bath salts”) was extended by the inclusion of benzodiazepine-type compounds.

Introduction

Benzodiazepines such as phenazepam and etizolam - which are still prescribed in some countries - were initially available on the Internet providing an attractive and alternative source to prescription- only benzodiazepines. In the last years, the group of so-called designer benzodiazepines has been enlarged by compounds that are either precursors (e.g. diclazepam) or active metabolites (e.g. norfludiazepam) of known benzodiazepines or that combine structural properties of different classical benzodiazepines (e.g. flubromazolam). Since patents and scientific literature describe the synthesis, and detail results of animal model studies, for more than a hundred different benzodiazepines, it can be assumed that this sub-group of NPS will extend quickly in the future. In this study we describe the workflow to augment the Toxtyper™ library with new compounds of interest such as synthetic drugs. In addition, we show how semi-quantitative results may be obtained within the Toxtyper screening workflow.