Metabolite identification detection strategies

This chapter discussed the common strategies used for characterization of metabolites of small-molecule compounds. In low-resolution MS such as triple quadrupole (QqQ) the detection of metaboUte often starts with CNL or PI as survey scans. The general approach for metabolite identification using triple quad MS involves the following steps ... 

The generation of Phase-I metabolites can be considered as a preparation for the Phase-II metabolism. The detection and identification of Phase-I metabolites is important, because possibly toxic metabolites are formed. Some metabolites are even more active than the dmg itself, either in the action the dmg was administered for or in toxic side effects. Administration of a prodrag with more favourable properties is sometimes performed. The prodrag is rapidly transformed in the actual active substance. Moreover, in quite a number of cases the analytical strategy is directed at identification of the Phase-I metabohtes, even after chemical or enzymatic deconjugation of the Phase-II metabolites. 

Other strategies would be highly useful to apply a wide-scope screening for other compounds of interest. LC-QTOF in MS acquisition mode is much more appropriate for this goal as most of drags of abuse and their metabolites are LC-amenable, and QTOF offers useful relevant information for a reliable identification of compoimds detected in samples. By means of specialized software and appropriate compoimd database, accurate mass information can be processed after MS fuU acquisition using mass error and retention times, when available. This approach allows a safe identification of the compound detected, because of accurate mass data and fragmentation. 

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