MS-Based Molecular Networking of Designer Drugs as an Approach for the Detection of Unknown Derivatives for Forensic and Doping Applications: A Case of NBOMe Derivatives

Abstract

The NBOMe family is a group of new psychoactive substances (NPSs). In this study, the fragmentation patterns of NBOMe derivatives were analyzed using liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF/MS). The MS/MS spectral data was used to establish a molecular networking map for NBOMe derivatives. The fragmentation patterns of nine NBOMe derivatives were interpreted on the basis of their product ion spectral data. NBOMe derivatives generally showed similar product ion spectral patterns; among them, the halogen-substituted methoxybenzyl ethanamine type derivatives showed a characteristic product ion of a radical cation. Molecular network analysis of the MS/MS data revealed that all NBOMe derivatives formed one integrated networking cluster that discriminated them from other types of NPSs. NBOMe derivatives were spiked into human urine and identified by connection to the NBOMe database network. Furthermore, the NBOMe compounds that were not registered in the database were also recognized as an NBOMe-related substance by molecular networking. These results demonstrate the potential of using molecular networking-based screening methods for designer drugs, and the proposed method would be useful in forensic or doping analysis.

Diagnostic fragmentation‐assisted mass spectral networking coupled with in silico dereplication for deep annotation of steroidal alkaloids in medicinal Fritillariae Bulbus

“…12 It compares all MS/MS spectra in a given sample and groups them according to their similarity via the establishment of a modified cosine score; that is, structurally related compounds can be grouped into the same network, showing a substantial advantage in the discovery of structural analogs. 13 The use of characteristic fragmentation patterns from evidencebased learning of typical structures is a classic approach for compound identification. 15 Diagnostic fragment ions can be used to expertly annotate the substructures of unknown compounds that belong to the homologs of reported chemicals.…”

NBOMes–Highly Potent and Toxic Alternatives of LSD

“…25C-NBOMe and 25I-NBOMe, and their metabolites, were detected and identified by LC-QTOF-MS in DDA mode (Wohlfarth et al, 2017). Yu et al (2019) proposed a new method of NBOMes identification. The fragmentation patterns of nine NBOMe derivatives (25H-NBOMe, 25B-NBOMe, 25E-NBOMe, 25N-NBOMe, 25C-NBOH, 25I-NBOH, 25B-NBF, 25C-NBF, and 25I-NBF) were analyzed using LC-QTOF-MS and an approach known as molecular networking, one that organizes MS-MS data by mining the MS-MS fragmentation similarity.…”

In Vitro Metabolism of Donepezil in Liver Microsomes Using Non-Targeted Metabolomics

“…This new technique has been applied to determine the metabolic profile of amiodarone [ 13 ], isoniazid [ 14 ], itraconazole [ 15 ], ritonavir [ 16 ], and tolcapone [ 17 ] and has enabled the discovery of several new metabolites. In addition, molecular networking, which is currently used in various fields, such as natural product analysis, drug discovery, and drug metabolism, has been used as a tool for metabolite identification [ 18 , 19 ]. Molecular networking creates a network of compounds with structural similarities based on tandem MS data [ 18 , 19 ].…”

“…In addition, molecular networking, which is currently used in various fields, such as natural product analysis, drug discovery, and drug metabolism, has been used as a tool for metabolite identification [ 18 , 19 ]. Molecular networking creates a network of compounds with structural similarities based on tandem MS data [ 18 , 19 ]. In general, drug metabolites contain the primary backbone of the parent drug and exhibit a similar fragmentation pattern in the MS/MS spectrum [ 18 ].…”