*3.1.5 Mass defect-dependent acquisition*

This approach is useful for the detection of both common and uncommon drug metabolites by using a mass defect filter (MDF). Interference ions from matrices are easily filtered out by MDF, because their mass defects are outside the mass defect range of common drug metabolites [88]. MDF is commonly used as a post-acquisition data processing technique and major instrument vendors are incorporating this in the metabolite identification software packages. In the TripleTOF® (Sciex) instrument, MDF is used as a selection factor to trigger MS/MS acquisition. Fullscan HRMS data are analyzed by applying real time MDF and identifies precursor ions whose mass defects fall within a specific window of a MDF. These ions are automatically followed by MS/MS acquisition. A different class of metabolites is detected by using multiple MDFs. Multiple mass defects are calculated by the software based on the elemental compositions of the parent, phase II conjugates, dealkylation, and hydrolysis metabolites and simultaneously perform the multiple mass filtering. This approach is useful for the rapid identification of drug metabolites in complex biological samples [89].
