Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: Implications for nontargeted screening of designer drugs

Detection of new designer drugs remains an analytical challenge because of the ability of manufacturers to rapidly substitute closely related analogs for banned substances. Traditional targeted mass spectrometry methods rely on library searches, known masses, or multiple reaction monitoring (MRM) transitions and are therefore often unable to detect or identify recently discovered or yet unreported designer drug analogs. Here, high-resolution mass spectrometry in conjunction with mass defect filtering is presented as a method for nontargeted analysis to detect both known and novel analogs of designer drugs. The technique is applied in depth to a family of designer drugs composed of indole-derived synthetic cannabinoids closely related to JWH-018, a substance recently controlled in the United States. A single mass defect filter with a 50 mDa window encompasses over 80% of all currently published structures in this family. Searching for precursor ions of common fragment ions enables detection of compounds with mass defects that fall outside the range of mass defect filter parameters. Application of a mass defect filter to fragment ions prior to precursor ion searching increases the breadth of analogs that can be detected. The combined approach defines a broad-spectrum search for related molecules.

Grabenauer, M., Krol, W., Wiley, J., & Thomas, B. (2012). Analysis of synthetic cannabinoids using high-resolution mass spectrometry and mass defect filtering: Implications for nontargeted screening of designer drugs. Analytical Chemistry, 84(13), 5574-5581. DOI: 10.1021/ac300509h