Separation and Characterization
of Synthetic Cannabinoid
Metabolite Isomers Using SLIM High-Resolution Ion Mobility-Tandem
Mass Spectrometry (HRIM-MS/MS)
posted on 2024-02-16, 07:44authored byRalph Aderorho, Shadrack Wilson Lucas, Christopher D. Chouinard
Synthetic cannabinoids, a subclass of new psychoactive
substances
(NPS), are laboratory-made substances that are chemically similar
to those found naturally in the cannabis plant. Many of these substances
are illicitly manufactured and have been associated with severe health
problems, prompting a need to develop analytical methods capable of
characterizing both known and previously undetected compounds. This
work focuses on a novel Structures for Lossless Ion Manipulations
(SLIM) IM-MS approach to the differentiation and structural characterization
of synthetic cannabinoid metabolites, specifically MDA-19/BUTINACA,
JWH-018, and JWH-250 isomer groups. These different compound classes
are structurally very similar, differing only in the position of one
or a few functional groups; this yielded similarity in measured collision
cross section (CCS) values. However, the high resolution of SLIM IM
provided adequate separation of many of these isomers, such as sodiated
JWH-250 metabolites N-4-OH, N-5-OH, and 5-OH, which displayed CCS
of 187.5, 182.5, and 202.3 Å2, respectively. In challenging
cases where baseline separation was precluded due to nearly identical
CCS, such as for JWH-018 isomers, simple derivatization by dansyl
chloride selectively reacted with the 6-OH compound to provide differentiation
of all isomers using a combination of CCS and m/z. Finally, the opportunity to use this method for structural
elucidation of unknowns was demonstrated by using SLIM IM mobility-aligned
MS/MS fragmentation. Different MDA-19/BUTINACA isomers were first
mobility separated and could then be individually activated, yielding
unique fragments for both targeted identification and structural determination.
Overall, the described SLIM IM-MS/MS workflow provides significant
potential as a rapid screening tool for the characterization of emerging
NPS such as synthetic cannabinoids and their metabolites.