Strategies for characterization of drug metabolites using liquid chromatography-tandem mass spectrometry in conjunction with chemical derivatization and on-line H/D exchange approaches.
Strategies using high performance liquid chromatography-tandem mass spectrometry (LC-MS/MS) in conjunction with techniques such as chemical derivatization and on-line hydrogen/deuterium (H/D) exchange for structural elucidation of drug metabolites in crude samples are reviewed. Useful mass spectrometric scan techniques discussed include product ion scan, constant neutral-loss scan, precursor ion scan, multistage MS(n), and accurate mass measurements. In biological systems, xenobiotics are transformed into metabolites, which usually involves introduction of one or more polar functional groups or removal or blockage of such structural moieties. Therefore, chemical derivatization strategies for determination of functional groups and on-line H/D exchange approaches for probing number of exchangeable hydrogens are powerful tools for structural elucidation of drug metabolites in drug metabolism studies. More importantly, these experiments can be carried out on crude samples in microscale, providing sufficient material for LC-MS/MS analysis. Therefore, labor intensive and technically challenging purification of low levels of drug metabolites from complex biological matrices can be avoided. It is the authors' conclusion that strategies such as chemical derivatization and on-line H/D exchange should be used more routinely in drug metabolism studies in order to facilitate metabolite identification.
Liu
David Q
DQ
Analytical Sciences, GlaxoSmithKline, UW2940, P.O. Box 1539, 709 Swedeland Road, King of Prussia, PA 19406, USA. david.q.liu@gsk.com
Hop
Cornelis E C A
CE
D002853:Chromatography, Liquid / Q000379:methods; D041961:Deuterium Exchange Measurement / Q000379:methods*; D013058:Mass Spectrometry / Q000379:methods; D004364:Pharmaceutical Preparations / Q000032:analysis* / Q000737:chemistry / Q000378:metabolism*
D004364:Pharmaceutical Preparations