Exhaled breath carries aerosol micro-particles containing nonvolatile organic substances. Recently, the analysis of drugs of abuse (DOA) have become of interest in exhaled breath particles (EBP). In this study, a liquid chromatography – tandem mass spectrometry (LC–MS/MS) method was developed and validated to analyze 28 DOA in 30 L of EBP collected on a permeable polymer filter. After extraction, the chromatographic separation was achieved on a UPLC BEH phenyl column using a mobile phase consisting of methanol and water both containing 4 mmol/L ammonium formate and 0.05% ammonia. The column temperature was set at 50 °C and mobile phase flow rate 0.5 mL/min in gradient mode with a total run time of 5 min. The mass spectrometer was operated in positive electrospray ionization and selected reaction monitoring mode. Acquired limits of quantification were in the range of 1–66 pg/filter for all substances except DM-tramadol. Excellent linearity over the concentration range from LLOQs – 15 ng/filter with r2 values >0.99 and satisfactory recoveries (70–116% at 100 pg/filter) were achieved. During method application a total 26 samples were analyzed of which 24 were found to be positive for 13 analytes. The highest amount was found for methadone (56 ng/filter) and the lowest amount was found for the methadone metabolite EDDP (2 pg/filter) in two different samples.