The influx of new psychoactive substances is a problem that is challenging the analytical capabilities of enforcement agencies. Cathinone designer drugs are less likely to be included in routine drug screens, and typical drug formulations are commonly mixtures with continually shifting components. Ambient ionization mass spectrometry employs relatively mild conditions to desorb and ionize solid samples, imparting much less energy than that associated with conventional mass spectrometry methods. In the current study, accurate mass determinations provided preliminary identification of the various components of drug mixtures. The data generated in forensic mass spectrometry can be used for both elemental composition formulations and isotope abundance calculations for determination of unknown psychoactive substances; and the study demonstrated how this data could be applied to the presence of new drugs as the active components shift in response to regulations. Isotope abundance calculations were used to develop a candidate pool of possible molecular formulas associated with cathinones as a specific class of designer drugs. Together, the combination of a time-of-flight (TOF) mass analyzer along with in-source collision-induced dissociation (CID) spectra were used to drastically narrow the pool of candidates to a single molecular formula. The [M + H]+ and product ion peaks provided data for presumptive analysis of various substituted synthetic cathinones in a manner that is complementary to conventional GC-MS analysis of new psychoactive substances. (Publisher abstract modified)