A method for generating a searchable small-molecule tandem mass spectrometry library comprising: (a) generating, by theoretical calculation and for each of a plurality of small-molecule compounds, a list of ion species, including fragment-ion species that are predicted, by the theoretical calculations, to be generated by tandem mass spectrometry (MS n) analyses of the small molecule compounds, where n ≥ 2, wherein the predicted ion species that correspond to each small molecule compound are grouped into nodes (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27) of a respective fragmentation tree (10, 71), each node (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27) of each fragmentation tree (10, 71) corresponding to predicted production of one or more predicted fragment ion species by fragmentation of another of the predicted ion species, and wherein each predicted ion species of each node (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27) is linked, by means of a predicted fragmentation pathway, to at least one other predicted ion species of another node (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27); (b) comparing at least a subset of the predicted ion species to entries in a database that includes a list of experimentally observed ion species; (c) matching a predicted mass-to-charge ratio ( m / z) value of each of one or more of the predicted fragment-ion species to a respective experimentally measured m / z value of an experimentally observed fragment-ion species for which information is tabulated in the database; and (d) updating one or more of the fragmentation trees (10, 71) based on information derived from the matched predicted and experimentally measured m / z values, wherein the updating comprises: - deleting experimentally-non-observed predicted ion species from a fragmentation tree (10, 71), or marking or annotating them as non-viable; and/or - deleting, or marking as non-viable all or a portion of a predicted fragmentation pathway that connects to an experimentally-non-observed predicted ion species from a fragmentation tree (10, 71), wherein the searchable small-molecule tandem mass spectrometry library comprises the updated fragmentation tree. (a) generating, by theoretical calculation and for each of a plurality of small-molecule compounds, a list of ion species, including fragment-ion species that are predicted, by the theoretical calculations, to be generated by tandem mass spectrometry (MS n) analyses of the small molecule compounds, where n ≥ 2, wherein the predicted ion species that correspond to each small molecule compound are grouped into nodes (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27) of a respective fragmentation tree (10, 71), each node (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27) of each fragmentation tree (10, 71) corresponding to predicted production of one or more predicted fragment ion species by fragmentation of another of the predicted ion species, and wherein each predicted ion species of each node (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27) is linked, by means of a predicted fragmentation pathway, to at least one other predicted ion species of another node (1, 2.1 - 2.3, 3.1 - 3.9, 4.1 - 4.27); (b) comparing at least a subset of the predicted ion species to entries in a database that includes a list of experimentally observed ion species; (c) matching a predicted mass-to-charge ratio ( m / z) value of each of one or more of the predicted fragment-ion species to a respective experimentally measured m / z value of an experimentally observed fragment-ion species for which information is tabulated in the database; and (d) updating one or more of the fragmentation trees (10, 71) based on information derived from the matched predicted and experimentally measured m / z values, wherein the updating comprises: - deleting experimentally-non-observed predicted ion species from a fragmentation tree (10, 71), or marking or annotating them as non-viable; and/or - deleting, or marking as non-viable all or a portion of a predicted fragmentation pathway that connects to an experimentally-non-observed predicted ion species from a fragmentation tree (10, 71), - deleting experimentally-non-observed predicted ion species from a fragmentation tree (10, 71), or marking or annotating them as non-viable; and/or - deleting, or marking as non-viable all or a portion of a predicted fragmentation pathway that connects to an experimentally-non-observed predicted ion species from a fragmentation tree (10, 71),