Sonic spray (SS) ionization is a relatively novel atmospheric pressure ionization technique for LC/MS, based on the principle of "spray ionization", which only recently became commercially available. In this paper, we evaluate the performance of this ion source as an interface for LC/MS in comparison with the more traditional and better studied pneumatically assisted electrospray or ion spray (IS). The effect of organic modifiers, volatile acids, and buffer systems in the LC eluent on the ionization efficiency of both interfaces is described and some possible explanations for the observed phenomena are highlighted. We could conclude that the presence of organic solvents gradually increased the ionization efficiency for IS and SS, while volatile acids or buffers gave a significant signal suppression. Furthermore, we present the application of the sonic spray interface to a fast LC/MS analysis, for the simultaneous determination of the seven prime opium alkaloids in heroin impurity profiling. Chromatographic separation is performed in 5 min on a monolithic silica column (Chromolith Performance) with a gradient elution system and an optimized flow of 5 mL/min. By means of a postcolumn split of approximately 1/20, a coupling between the fast LC system and the mass spectrometer is made. The method is validated and successfully applied to the analysis of real-time seized heroin street samples.