This work describes the first analytical method specifically developed for the multianalyte determination of several drugs of abuse and their metabolites in air. The methodology is based on pressurized liquid extraction (PLE) of atmospheric particles collected by means of high volume sampler equipped with quartz microfiber filters and subsequent analysis of the extracts by liquid chromatography-tandem mass spectrometry (LC-MS/MS). Up to 17 different compounds belonging to five different chemical classes (cocainics, amphetamine-like compounds, opioids, cannabinoids, and lysergic compounds) are determined by means of this methodology. Acquisition is performed in the selected reaction monitoring (SRM) mode recording two transitions per compound (except for amphetamine). Quantitation by the internal standard method is based on the use of surrogated deuterated standards. The method has been validated in terms of linearity, accuracy, repeatability and sensitivity with satisfactory results. Absolute recoveries were above 50% for most investigated compounds. Method precision showed relative standard deviations (RSD) below 13% for all compounds, except for cannabinoids. The method limits of determination ranged from 0.35 pg/m(3) (for 2-oxo-3-hydroxy-LSD) to 22.55 pg/m(3) (for 11-nor-9 carboxy THC). Finally, as a part of the method validation, the optimized procedure was applied to the analysis of ambient air samples (fine grain-size particulates, PM(2.5)) collected at two urban background sites in Barcelona and Madrid (Spain). Results evidenced the presence of cocaine, benzoilecgonine, tetrahydrocannabinol, ecstasy, amphetamine, methamphetamine, and heroin in some or all of the samples investigated. The highest mean daily levels corresponded to cocaine (850 pg/m(3)) followed by heroin (143 pg/m(3)).