PT  - JOURNAL ARTICLE
AU  - Mingshe Zhu
AU  - Li Ma
AU  - Donglu Zhang
AU  - Kenneth Ray
AU  - Weiping Zhao
AU  - W. Griffith Humphreys
AU  - Gary Skiles
AU  - Mark Sanders
AU  - Haiying Zhang
TI  - Detection and Characterization of Metabolites in Biological Matrices Using Mass Defect Filtering of Liquid Chromatography/High Resolution Mass Spectrometry Data
AID  - 10.1124/dmd.106.009241
DP  - 2006 Oct 01
TA  - Drug Metabolism and Disposition
PG  - 1722--1733
VI  - 34
IP  - 10
4099  - http://dmd.aspetjournals.org/content/34/10/1722.short
4100  - http://dmd.aspetjournals.org/content/34/10/1722.full
SO  - Drug Metab Dispos2006 Oct 01; 34
AB  - An improved mass defect filter (MDF) method employing both drug and core structure filter templates was applied to the processing of high resolution liquid chromatography/mass spectrometry (LC/MS) data for the detection and structural characterization of oxidative metabolites with mass defects similar to or significantly different from those of the parent drugs. The effectiveness of this approach was investigated using nefazodone as a model compound, which is known to undergo multiple common and uncommon oxidative reactions. Through the selective removal of all ions that fall outside of the preset filter windows, the MDF process facilitated the detection of all 14 nefazodone metabolites presented in human liver microsomes in the MDF-filtered chromatograms. The capability of the MDF approach to remove endogenous interferences from more complex biological matrices was examined by analyzing omeprazole metabolites in human plasma. The unprocessed mass chromatogram showed no distinct indication of metabolite peaks; however, after MDF processing, the metabolite peaks were easily identified in the chromatogram. Compared with precursor ion scan and neutral loss scan techniques, the MDF approach was shown to be more effective for the detection of metabolites in a complex matrix. The comprehensive metabolite detection capability of the MDF approach, together with accurate mass determination, makes high resolution LC/MS a useful tool for the screening and identification of both common and uncommon drug metabolites. The American Society for Pharmacology and Experimental Therapeutics