Deuterium-labeled analogues are available for a variety of drugs, but the amphetamines (amphetamine and methamphetamine) have more options available than any other drug. The analytical method and circumstances of its use can have a significant impact on the decision of what is the best internal standard to use. More than one method can give acceptable results; however, some circumstances can make a given internal standard a poor choice for a particular analysis. Increased choices of available candidates make the evaluation of an internal standard even more difficult. Thorough evaluation of the available options is a major undertaking and is presented here to assist laboratories in selection of the most appropriate internal standard for their individual needs. All commercially available deuterated analogues to amphetamine and methamphetamine were evaluated as part of this study. in addition, nonisotopically labeled propylamphetamine was also evaluated for comparison purposes. The compounds were analyzed underivatized and derivatized with trifluoroacetic anhydride, pentafluoropropionic anhydride, heptafluorobutyric anhydride, and 4-carbethoxyhexafluorobutyryl chloride on HP-1, HP-5, and DB-I 7 capillary columns. Mass spectral analysis revealed that several of the internal standards were not viable for monitoring ions typically associated with selected ion monitoring analysis of amphetamine and methamphetamine. These included amphetamine-d3 (1-phenyl-2-aminopropane-3,3,3-d3) and amphetamine-d5 (phenyl-d5), neither of which exhibits three unique ions. The d3 standard shares the common ion at m/z 91, acid d5 (phenyl) shares the base peak ion with derivatized amphetamine. Although methamphetamine-d6 and methamphetamine-d10 show three unique ions, they do not allow monitoring of the ion fragments typically used for methamphetamine. Evaluation of the limit of detection, linear range, and within-run and between-run variability was accomplished for each viable internal standard.