identified in the ion chromatogram (Fig. 11.5b). In addition, mass spectra of
the metabolite peaks were greatly simplified after MDF processing. The
protonated molecule of M3 was embedded amongst many other predominant
endogenous ions in the unprocessed spectrum (Fig. 11.6a). After applying
MDF, the majority of the interference ions were removed and the protonated
molecule of M3 became predominant in the mass spectrum (Fig. 11.6b).
Mass defect filter is solely dependent on the availability of accurate mass
data. Therefore, it can detect unusual metabolites resulting from novel
biotransformation pathways and is especially useful in metabolite profiling
studies when radiolabeled drug is not available.
11.6 ADDITIONAL MS-RELATED TECHNIQUES FOR METABOLITE
IDENTIFICATION
11.6.1 LC/NMR/MS
Although mass spectrometry (LC/MS and LC/MS/MS) is by far the most
widely used technique for metabolite profiling and identification, it does not
always provide sufficient information for unequivocal structural elucidation of
metabolites. NMR spectroscopy is an excellent complementary tool for
FIGURE 11.6 Mass spectra of omeprazole metabolite M3 in plasma obtained by
Q-TOF LC/MS without (a) and with (b) MDF processing (chromatograms shown in
Fig. 11.5). Reprinted from Zhu et al. (2006) with permission of the American Society for
Pharmacology and Experimental Therapeutics.
348 APPLICATION OF LIQUID CHROMATOGRAPHY/MASS SPECTROMETRY