Filters/filtering mass defect

One of the more powerful techniques is a new software tool called mass defect filtering.176 185-188 A mass defect can be defined as the difference between the exact mass and nominal mass of a compound.189 Typically, drug-like molecules (and their metabolites) will have mass defects that differ from those of endogenous matrix materials. While a mass spectrometer that has unit mass resolution cannot differentiate a test compound from an isobaric matrix compound, a high mass resolution MS may be able to differentiate many isobaric matrix compounds from test compounds. 

Figure 7.13 illustrates the utility of mass defect filtering (also known as exact mass filtering) and UPLC. It shows results of UPLC/MS assay of a bile sample containing buspirone and its metabolites.184 The top trace shows the (unfiltered) TIC for the sample the middle trace is the result of an exact mass filter the bottom trace is an extracted ion chromatogram for the M+16 or hydroxylated metabolites based on their exact masses. It is readily apparent that this new software tool may be very helpful for metabolite identification studies. 

FIGURE 7.12 Metabolite profile of bile sample obtained from a dog dosed with 20 mg/kg of a 14C-labeled test compound (A) total mass chromatogram of unprocessed LC/MS data (B) total mass chromatogram after mass defect filter processing (C) radioactivity chromatogram. (Source Adapted from Zhang, H.D. and Ray, K J. Mass Spectrom., 2003, 38, 1110. With permission of John Wiley Sons.)... 

Fig. 1.42 LC-MS profile of omeprazole metabolites spiked in plasma (A) without mass defect filter, (B) with mass defect filter. Peaks Ml mono-oxidation metabolite [-H6 u, Mass defect (MD) - -5 milliunits], M2 reduction and demethylation (—30 u, MD -HO milliunits), M3 mono-oxidation metabolite (-H6 u, MD —5 milliunits), M4 reduction (—16 u, - -5 milliunits), MS mono-oxidation metabolite (-H6 u, 4-5 milliunits). Adapted with permission from reference [85].

Detection and characterization of metabolites in biological matrices using mass defect filtering of liquid chromatography/high resolution mass spectrometry data. Drug Metab. Dispos. 2006, 34, 1722. 

Bateman, K. P., Castro-Perez, J., Wrona, M., Shockcor, J. P., Yu, K., Oballa, R., and Nicoll-Griffith, D. A. (2007). MSE with mass defect filtering for in vitro and in vivo metabolite identification. Rapid Commun. Mass Spectrom. 21 1485-1496. 

Mortishire-Smith, R. J., Hill, A., and Castro-Perez, J. M. (2007). Generic dealkylation A tool for increasing the hit-rate of metabolite identification, and customizing mass defect filters. In Proceedings of the 55th ASMS Conference on Mass Spectrometry and Allied Topics, Indianapolis, IN. 

Zhu, M., Ma, L., Zhang, H., and Humphreys, W. G. (2007). Detection and structural characterization of glutathione-trapped reactive metabolites using hquid chromatography-high-resolution mass spectrometry and mass defect filtering. Anal. Chem. 79 8333-8341. 

Zhang, H., Ray, K., Ma, L., Zhang, D., Drexler, D., and Sanders, M. (2005a). Applicability of mass defect filters (MDF) to drug metabolite detection in biological matrices. In Proceedings of the 53rd ASMS Conference on Mass Spectrometry and Allied Topics, San Antonio, TX. 

High-Resolution LC-MS-Based Mass Defect Filter Approach Basic Concept and Application in Metabolite... 

HIGH-RESOLUTION LC-MS-BASED MASS DEFECT FILTER APPROACH... 

To reflect the underlining principle of the approach, it is referred to as a mass defect filter, although in practice it works on residual masses of ions. For the simplicity of this chapter, the term mass defect is used to refer to the characteristic residue mass of a molecular species. 

In addition, as previously illustrated in Fig. 6.1, multiple filters may be established for a single data set, each corresponding to a different mass range, to provide for the examination of a wide range of mass defects resulting from diverse components. (The use of multiple filters may be necessary for such samples because of the metabolic transformations of the molecular species to be investigated.) The parameters for the MDF can be defined prior to examination of the acquired data, based solely on the mass defect of the chug and the expected variation in the mass defects of its related modifications. The MDF parameters can also be defined after examination of the acquired data based on observed trends in the actual acquired data (e.g., the likelihood that interferences will have mass defects similar to that of the metabolites of interest). 

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