The isomers 4-methylethcathinone and N-ethylbuphedrone are substitutes for the recently banned drug mephedrone. We find that with conventional proton transfer reaction mass spectrometry (PTR-MS), it is not possible to distinguish between these two isomers, because essentially for both substances, only the protonated molecules are observed at a mass-to-charge ratio of 192 (C12 H18 NO(+) ). However, when utilising an advanced PTR-MS instrument that allows us to switch the reagent ions (selective reagent ionisation) from H3 O(+) (which is commonly used in PTR-MS) to NO(+) , O2 (+) and Kr(+) , characteristic product (fragment) ions are detected: C4 H10 N(+) (72 Da) for 4-methylethcathinone and C5 H12 N(+) (86 Da) for N-ethylbuphedrone; thus, selective reagent ionisation MS proves to be a powerful tool for fast detection and identification of these compounds.