Here we present an in silico IR spectral library of molecular ions, compatible with IRIS and hence LC-MS workflows. This library was compiled by coupling a standardized workflow for calculating vibrational spectra at the DFT-level to the human metabolome database (HMDB) . This workflow requires only a simple chemical identifier as input to automatically generate relevant IR spectra. This workflow is applied to entries in the HMDB with molecular weights <210 Da. We present benchmark tests of this in silico library using a new, extensive set of 189 experimental IRIS spectra, derived from 87 unique metabolites. We demonstrate that the specificity of the IR fingerprint not only allows for the identification of known unknowns, but also enables de novo structural elucidation of unknown unknowns.