Characterization of hallucinogenic phenethylamines using high‐resolution mass spectrometry for non‐targeted screening purposes

Abstract

Hallucinogenic phenethylamines such as 2,5-dimethoxyphenethylamines (2C-X) and their N-(2-methoxybenzyl) derivatives (25X-NBOMe) have seen an increase in novel analogues in recent years. These rapidly changing analogues make it difficult for laboratories to rely on traditional targeted screening methods to detect unknown new psychoactive substances (NPS). In this study, twelve 2C-X, six 2,5-dimethoxyamphetamines (DOX), and fourteen 25X-NBOMe derivatives, including two deuterated derivatives (2C-B-d and 25I-NBOMe-d ), were analyzed using ultra-performance liquid chromatography coupled with quadrupole time-of-flight mass spectrometry (UPLC-QTOF-MS). Collision-induced dissociation (CID) experiments were performed using collision energies set at 10, 20, and 40 eV. For 2C-X and DOX derivatives, common losses were observed including neutral and radical losses such as NH (17.0265 Da), •CH N (32.0500 Da), C H N (45.0578 Da) and C H N (47.0735 Da). 2C-X derivatives displayed common product ions at m/z 164.0837 ([C H O ] ), 149.0603 ([C H O ] ), and 134.0732 ([C H O] ) while DOX derivatives had common product ions at m/z 178.0994 ([C H O ] ), 163.0754 ([C H O ] ), 147.0804 ([C H O] ), and 135.0810 ([C H O] ). 25X-NBOMe had characteristic product ions at m/z 121.0654 ([C H O] ) and 91.0548 ([C H ] ) with minor common losses corresponding to 2-methylanisole (C H O, 122.0732 Da), 2-methoxybenzylamine (C H NO, 137.0847 Da), and •C H NO (152.1074 Da). Novel analogues of the selected classes can be detected by applying neutral loss filters (NLFs) and extracting the common product ions. Copyright © 2017 John Wiley & Sons, Ltd.

In vitro phase I metabolism of three phenethylamines 25D‐NBOMe, 25E‐NBOMe and 25N‐NBOMe using microsomal and microbial models

“…For the 25X‐NBOMe parent compounds, the respective precursor ions and the product ions with m/z 121.0653 and m/z 91.5048 (representing the NBOMe part) were present. The product ions resulted due to amine cleavage of the NBOMe moiety forming [C 8 H 9 O] + ( m/z 121.0653) and further demethoxylation via neutral loss of formaldehyde forming the tropylium ion [C 7 H 7 ] + ( m/z 91.0548) . These product ions were consistent with previously published data on 25B‐NBOMe, 25C‐NBOMe, and 25I‐NBOMe, because the alterations between the 25X‐NBOMe are on the 2C part at the 4‐position .…”

Collision-Induced Dissociation Studies of Synthetic Opioids for Non-targeted Analysis

“…From this perspective, methods that take a more holistic approach to the detection of compounds structurally related to known classes of NPS have the distinct advantages over traditional targeted methods. These non-targeted approaches are required for the detection and tentative identification of novel analogs that have not been recorded previously (Pasin et al, 2017a). Samples where these kinds of detections arise can then be flagged for further confirmatory analysis when appropriate CRMs are available.…”

“…If an MS technique with a high enough mass resolution was used, however, the accurate masses for those fragments of 17.0265 and 17.0027 Da respectively could be determined and therefore the losses differentiated. The effectiveness of collision-induced dissociation (CID) data for the development of non-targeted detection strategies has been previously demonstrated for different drug classes (Pasin et al, 2017a).…”

Current applications of high-resolution mass spectrometry for the analysis of new psychoactive substances: a critical review

“…Grabenaurer et al [78] introduced the concept of precursor ion searching, explaining that structurally related compounds can have the same product ions and that novel analogues could be detected by searching for the precursor ions of common product ions. Recently, Pasin et al [86] reported the characterization of hallucinogenic phenethylamines using HRMS for non-targeted screening, identifying that common product ions and neutral losses could be monitored using basic data processing techniques such as product ion searching and neutral loss filtering (NLF). Figure 5 illustrates the use of NLF with precursor neutral loss chromatograms (pNLC).…”

“…As mentioned previously, the efficacy of bottom-up approaches largely relies on the acquisition of MS/MS and it has been suggested that DIA techniques should be used rather than DDA [86]. The major limitation of this approach is that it requires data processing software capable of generating numerous EICs for characteristic product ions, if monitoring all potential NPS classes.…”