Stereospecific Drug Metabolite Analysis Using 2D LC/MS Q-TOF

Agilent logoDrug metabolite identification and quantitation is critical to drug discovery and development. Additionally, new regulatory guidance re-emphasizes the role of drug metabolite identification and a stereospecific understanding of the pharmacokinetic properties of the drug candidates and their major human metabolites.

Many drug lead compounds have one or multiple chiral centers and their oxidative metabolism could introduce further chirality in the molecule. These stereoisomers could be formed in different abundances and hence quantifying each individual stereoisomeric metabolite would be important. Isomeric metabolites can be of similar physicochemical properties and consequently may coelute. Also, these isomeric metabolites often have the same molecular weight, presenting an additional analytical challenge for bioanalysts. One extremely powerful approach to resolving stereoisomeric metabolites of close physicochemical properties, is to resolve them using powerful chromatography ahead of mass spectrometric analysis.

In this webinar we will present a simple, easy to use 2D LC/MS Q-TOF setup for achieving achiral followed by chiral resolution of stereoisomeric oxidative metabolites. We will illustrate this approach with real world examples from microsomal and hepatocyte incubations.

What will you learn:

  1. The importance of stereospecific analytical methods in drug metabolite analysis
  2. A brief overview of 2D chromatography: heart cutting (LC-LC) versus comprehensive 2D (LC × LC) methods
  3. An overview of the Agilent 1290 Infinity 2D LC system
  4. Multi heart cutting made easy
  5. Stereospecific analysis of Phase I metabolism of racemic drugs using 2D LC/MS Q-TOF

Who attended:

  • ADME/PK researchers
  • Laboratory managers and scientists focused on ADME/PK research, specifically, drug metabolite quantitation and identification in Biotech, Pharmaceutical companies and CRO’s
  • Project leaders, medicinal chemists and biologists interested in obtaining critical structure and quantitation data on their drug candidates to drive their drug discovery programs forward
  • Academicians and students interested in drug metabolite quantitation and identification

Speaker biographies:

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Murali Subramanian
Senior Principal Investigator
Biocon Bristol-Myers Squibb Research Centre (Syngene International)

Murali Subramanian, PhD, received his bachelor’s degree in Chemical Engineering from National Institute of Technology (Karnataka) and his PhD in Chemical and Biological Engineering from Iowa State University in the field of metabolic engineering and phytoremediation. He completed a postdoc with Prof Rory Remmel and Prof Timothy Tracy at the University of Minnesota in the field of drug metabolism and bioanalysis. He is currently working in Biocon Bristol Myers Squibb Research Center (Bangalore) in the pharmaceutical candidate optimization department with specialization in the biotransformation division. He has published over 15 articles and book chapters in international peer reviewed books and journals.

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Smriti Khera
Global Pharmaceutical Segment Manager
Agilent Technologies, Inc.

Smriti Khera, Ph.D received her bachelor’s degree in chemistry from Ferguson College, Pune in 2000. Thereafter, she received a Ph.D. degree in Medicinal and Natural Products Chemistry at the University of Arizona under the direction of Dr. Barbara Timmermann in 2005. She then spent seven years at Amgen as a Senior Scientist in the Molecular Structure group managing an analytical laboratory in support of small molecule drug discovery. Smriti joined Agilent in January 2012. At Agilent, she is responsible for championing Agilent’s product portfolio for Pharmaceutical applications and workflows through application centric technology integration across product platforms to provide turnkey workflow solutions.

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Syed Salman Lateef
Lead Application Scientist
Agilent Technologies, Inc.

Syed Salman Lateef, PhD received his bachelor’ degree in Biochemistry from University of Illinois at Chicago and his PhD in Analytical Chemistry from the same university in the field of surface chemistry and analysis.  He then spent three and half years at University of Illinois Protein Core Facility as Senior Scientist involved in peptide synthesis, purification and characterization by LC/MS methods.  In 2006 he joined Morton Grove Pharmaceutical, Illinois as a scientist involved in method development and quality control of generics.  Salman joined Agilent in 2007 and is currently working as a Lead Application Scientist.  His primary focus is to develop applications and workflow solutions across platforms.  He has published several applications note in the area of small molecule Pharma and Metabolomics.

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Jens Trafkowski
Product Manager Analytical HPLC
Agilent Technologies, Inc.

Jens received his PhD at the Institute of Forensic Medicine, focusing on LC-MS/MS applications in forensic and clinical toxicology. He also studied food chemistry at the University of Bonn, Germany.  He was an LC-MS application specialist at Waters and AB SCIEX in the Almere (The Netherlands) and Darmstadt (Germany), and has been with Agilent Technologies since October 2011, working as product Manager for Analytical HPLC  in Waldbronn (Germany), responsible for analytical flow pumps, degassers and the 1290 Infinity 2D-LC Solution.