A computationally supported designer benzodiazepine strategy for public toxicology laboratories.

This article focuses on a comprehensive strategy developed by the Cuyahoga County Regional Forensic Science Laboratory (CCRFSL) to detect and interpret designer benzodiazepines (DBZDs) in forensic casework. The approach integrates cross-reactivity studies using the Immunalysis™ benzodiazepine (BZD) direct enzyme-linked immunosorbent assay (ELISA) kit, an expanded liquid chromatography–tandem mass spectrometry (LC–MS-MS) confirmation panel covering 40 BZD and Z-drug analytes, optimization of the method of standard addition (MSA) for quantitative analysis, and computational modeling to predict γ-aminobutyric acid type-A (GABAA) receptor binding affinity. This integrated method addresses challenges posed by the evolving DBZD market, limited potency data, and resource constraints in public laboratories, and is adaptable to other designer drug classes such as opioids, cannabinoids, and stimulants.