Dr. Cooper recently published an article in Analytical Chemistry:
Tandem mass spectrometry (MS/MS) can be used to identify metabolites in biological samples by searching against a library of spectra obtained from known compounds. But the best match from a library search is guaranteed to be incorrect if the unknown is not (yet) in any library. This paper presents a novel "hybrid" search method that returns a list of structurally similar compounds if the library contains "cognates" of the unknown: compounds with a structural difference confined to a single region of the molecule, that does not substantially alter its fragmentation behavior. Interpreting the resulting hit list can determine the chemical class and often the likely structure of the unknown.
The full article may be read here.
More information on Dr. Cooper's work may be found here.