This invention relates to a method and apparatus for separation of rare stable or radioactive isotopes from their atomic or molecular isobars in mass spectrometry (MS). In the present invention, the approach taken to removing atomic isobars utilizes a high transmission device for decelerating ions in combination with low energy reactions, such as ion-molecule reactions or near resonant electron transfer, in RF ion guides. The isobar is selectively depleted by electron transfer or other reactions between negative ions and gaseous targets in pressurized RF ion guides at low energies. The energy is controlled in such a way as to prevent reaction of the ion of interest while inducing reactions with the undesired isobar interference. The technique is of particular relevance to accelerator mass spectrometry (AMS) for which it allows substantial reductions in the necessary terminal voltage. The effect is to allow reductions in the size and cost of AMS installations.