Abstract: A device, system, and methods are disclosed for detecting the presence or determining a quantitative amount of at least one drug substance from exhaled breath of a subject in-situ. A collecting surface has a Surface Enhanced Raman Spectroscopy (SERS)-active layer that comprises at least one SERS-active material. The collecting surface is arranged as an outer surface of a waveguide for contact with exhaled breath, such that at least traces of said at least one drug substance in said exhaled breath can contact said SERS-active layer for read-out of a Raman shift spectrum that is detected in-situ for said detecting the presence or determining the quantitative amount of said at least one drug substance from said exhaled breath.