In this paper, we tried to better understand the challenge of unambiguous identification of fentanyl analogs by exploring the measurement diversity of these substances in NIST mass spectral libraries. We defined measurement diversity through the results of agglomerative hierarchical clustering and were able to identify that these analytes were most diverse when measured with DART-MS. Measurement diversity improved by combining multiple measurements, but still five pairs of compounds (mostly positional isomers) were indistinguishable with the standard measurements in NIST libraries. Designing custom/targeted methods or new mathematical approaches to characterize pairwise dissimilarity-including leveraging replicate measurementsare potentially fruitful approaches that will improve our ability to identify fentanyl analogs.