The Evolution Toward Designer Benzodiazepines in Drug-Facilitated Sexual Assault Cases

Abstract

Drug-facilitated sexual assault (DFSA) is a crime where the victim is unable to provide sexual consent due to incapacitation resulting from alcohol or drug consumption. Due to the large number of substances possibly used in DFSA, including illicit, prescription and over-the-counter drugs, DFSA faces many toxicological challenges. Benzodiazepines (BZDs) are ideal candidates for DFSA, as they are active at low doses, have a fast onset of action and can be easily administered orally. The last decade has seen the emergence of designer benzodiazepines (DBZDs), which show slight modifications compared with BZDs and similar pharmacological effects but are not controlled under the international drug control system. DBZDs represent an additional challenge due to the number of new entities regularly appearing in the market, their possibly higher potency and the limited knowledge available on their pharmacokinetic and pharmacodynamics properties. Many BZDs and DBZDs have a short half-life, leading to rapid metabolism and excretion. The low concentrations and short time windows for the detection of BZD in body fluids require the use of highly sensitive analysis methods to enable the detection of drugs and their respective metabolites. This review discusses the current state of the toxicological analysis of BZDs and DBZDs in forensic casework and their pharmacokinetic properties (i.e., absorption, distribution, metabolism, and elimination), as well as their analysis in biosamples typically encountered in DFSA (i.e., blood, urine and hair).

Figure 1.

General chemical structure of a 1,4-benzodiazepine (core formed by the combination of a benzene ring and a diazepine ring) with a 5-aryl substituent.

Figure 2.

Illustration of the Phase I metabolism of BZDs. A. Primary metabolic transformation pathways of the 1,4-benzodiazepine diazepam and chemical structures of its major metabolites. B. Primary metabolic transformation pathways of the 7-nitro-1,4-benzodiazepine clonazepam and chemical structures of its major metabolites.