Abstract: Forensic drug laboratories are inundated with cases requiring time-consuming GC- or LC-based chromatographic separations of submitted samples. High-throughput analytical methods would be of great practical utility within forensic drug analysis. Recently developed ion-mobility-based separation methods combined with mass spectrometry can often be used without chromatography, suppress chemical interferents of similar mass, and operate in seconds. We have evaluated differential mobility spectrometry–mass spectrometry (DMS-MS) for performance on adulterated cocaine mixtures. The DMS interface is only a few centimeters in length, operates in seconds, and can be adapted to any MS system using atmospheric pressure ionization. Drug cutting agents, typical targets such as cocaine, and drug metabolites are rapidly separated by the DMS ion prefilter. Tests demonstrated characterization of complex mixtures, such as isolation of levamisole, an adulterant with alarming side effects, from a 13-component mixture. DMS-MS holds great potential for the analysis of drug samples submitted for forensic analysis.