The main challenge in untargeted approaches is compound annotation and identification. One limitation with this is the size and quality of spectral libraries, especially as different types of mass spectrometers or collision energies yield different MS 2 spectra. Other techniques can be used for structural annotation of more features, such as in silico fragmentation, as seen here with more features annotated at Levels 3b and 3c than Levels 2 and 3a. However, in silico fragmentation has its own pitfalls as it is a computational prediction of MS 2 spectra. Moreover, in silico fragmentation techniques require reference structures as an input and thus would not be suitable for analytes which no structure has been previously described. Being able to elucidate structures from features of completely unknown analytes is extremely difficult, but combining various approaches, such as those described here, can yield valuable insight into the nature of these unknown features. Moreover, the use of complementary approaches can increase the confidence in their results.