Bella Coenen | 2026 I.S. Symposium
Name: Bella Coenen
Title: Detection of Designer Benzodiazepines via Mass Spectrometry-Based Molecular Networking
²Ñ²¹Âá´Ç°ù:ÌýBiochemistry & Molecular Biology
´¡»å±¹¾±²õ´Ç°ù:ÌýPaul Edminston
Drug-facilitated sexual assault poses a forensic and public health concern, due in part to the widespread use of sedative drugs like benzodiazepines (BZDs). Detection of BZDs in forensic samples is difficult as chemically modified versions can be used to evade traditional targeted methods. Molecular networking offers a spectral similarity-based technique capable of organizing MS/MS spectra into molecular ‘families’, enabling detection and subsequent clustering of unknown, but chemically related compounds into molecular networks. Since all BZDs share a core ring structure, there are similarities in MS/MS spectra across the BZD family. Thus, it is hypothesized that the MS/MS spectra of an assortment of chemically diverse BZDs and designer analogues can be detected by a spectral similarity algorithm called molecular networking. Reference MS/MS spectra for a panel of BZDs were generated using LC-QToF tandem mass spectrometry. These spectra were then used to construct a molecular network of all purchased BZDs via a cosine-similarity score-based tool called Global Natural Products Social Molecular Networking (GNPS). After successful network generation of BZD spectra, this network was compared to a second network that was generated containing data-dependent acquired MS/MS spectra from a human serum sample absent of BZDs. No false connections between BZDs and endogenous metabolites were created, even with a low modified cosine score of 0.2 being imposed. Finally, spectra from a designer BZD not included in the initial BZD network was spiked into an additional human serum sample, and the BZD-only network successfully recognized this novel compound as a BZD with connections to the BZD network ranging from modified cosine scores of 0.52-0.9. These findings demonstrate that MS/MS-based molecular networking can identify and group benzodiazepines, even in highly complex biological matrices, supporting its utility for rapid screening and forensic toxicology applications.
Posted in Symposium 2026 on May 1, 2026.
