Fast and accurate screening of biological samples is an important step in forensic toxicology for further decisions regarding possible quantification of the detected compounds in body fluids or tissues, investigations and prosecution. Based on Quadrupole Time-of-Flight (QqTOF) mass spectrometers – which are capable of acquiring complete MS and MS/MS spectra at a rate of 20 Hz or more and high mass accuracy – a new screening methodology was developed, validated and implemented in the forensic toxicological workflow. Urine samples were diluted with a mixture of water / acetonitrile / formic acid / ammonium formate (97.5 / 2.5 / 0.1% / 2.5 mM) and three internal standards were added (EME-D3, Tramadol-D3C13, THC-D3). Blood or plasma samples were prepared by protein precipitation. The samples were injected onto a core shell column (Phenomenex Kinetex C8, 50 x 2.1 mm, 2.6 μm) and analyzed on a QqTOF instrument (5600 TripleTOF, AB Sciex, Concord, Canada) with typical run times of 15 minutes from injection to injection. The methodology is based on sequential window acquisition of all theoretical fragment ions spectra (SWATH) and high resolution/high accuracy reference spectra which are used for data processing. Several forensic cases and applications are presented and the impact of this mass spectrometry based technique in the field of forensic toxicology is discussed.