Hybrid Mass Analyzers in Drug Metabolism Applications

Among the analytical techniques used in the biopharmaceutical industry, liquid chromatography mass spectrometry (LC-MS) assays are highly sought out by the drug metabolism and pharmacokinetic (DMPK) scientists due to their sensitivity, selectivity, specificity, and speed. Some of the desired qualities of the individual mass analyzers (quadrupole mass filters, ion traps and time-of-flights) and ion manipulation techniques are combined into one instrument to configure hybrid mass spectrometers. Such hybrid mass spectrometers become even more selective and specific when either time-of-flight or Fourier transform based high resolution mass spectrometers (HRMS) are combined with either ion traps or quadrupole mass filters. HRMS-based hybrid mass analyzers, including quadrupole- time-of-flights, linear ion trap-orbitrap, and quadrupole-orbitrap, have begun to become front line mass spectrometers across the biopharmaceutical industry, especially in the DMPK laboratories. The focus of this book chapter is hybrid mass spectrometers based strategies and procedures available for detection and characterization of xenobiotics at various stages of drug discovery and development. Keywords: high resolution mass spectrometry (HRMS); drug metabolism; pharmacokinetics; qual/quant; mass defect filter; isotope pattern filter; background subtraction