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Oxidative metabolism

ROXY

ROXY EC/MS for mimicing natures redox reactions.

ROXY EC/LC System upfront MS
mimicing natures redox reactions

 

 

The on-line coupling of Electrochemistry (EC) with LC/MS has shown great potential for the investigation of drug metabolism. It offers fast electrochemical synthesis of drug metabolites for reliable quantification by mass spectrometry (MS) to be operated as a high throughput screening system. The system is suitable to mimic (synthesize) phase I metabolites within minutes, that otherwise are obtained by time consuming in vivo (laboratory animals) or in vitro experiments (isolated liver cells, microsomes).

A pre-injection on-line electrochemical cell has been used to mimic liver metabolism. Metabolites are instantaneously generated and analysed. Briefly, a syringe pump is used to flush xenobiotics through an electrochemical cell to fill an injection loop. The oxidation products are injected and analysed using HPLC-MS.

Comparing Fig. 1 and 2 clearly indicates that the electrochemical simulation leads to all metabolites also found in conventional method making it a perfect tool for Metabolism.

Electrochemical simulation

 

Mass traces of Tetrazepam metabolites formed in the electrochemical reaction cell of the ROXY™ EC/LC system.

Microsomal approach


Mass traces of Tetrazepam metabolites formed by the microsomal approach. Experiments were performed using pooled rat liver microsomes from male Sprague Dawley rats. Courtesy: A. Baumann, B. Schubert, H. Oberacher and U. Karst, University Münster, Münster, Germany.


Application Notes

  • 210_000_00 - Oxidation of FAME (Biodiesel)
  • 210_001A_07 - ROXY Event programming and Settings
  • 210_001_10 - Fast Mimicking Phase 1 and 2 Acetaminophen
  • 210_002A_04 - Userdefined programs for AS 110
  • 210_002_04 - Automated Screening on REDOX Reactions
  • 210_003_00 - Superior Characterization of Protein Therapeutics
  • 210_004_07 - Oxidative Metabolism Amodiaquine
  • 210_005_04 - Synthesis of mg Quantities
  • 210_006_04 - Reduction of Disulfide Bonds in Proteins
  • 210_007_03 - Generation of Oxysterols
  • 210_008_03 - Reduction and Engineering of mAbs
  • 210_009_04 - Electrochemical Reduction of Biopharmaceuticals in HDXMS
  • 210_010_03 - Monitoring Electrochemical Reduction
  • 210_011_01 - EC Synthesis in flow & batch reactors
  • 210_012_01 - Triclosan Metabolism,Transformation
  • 210_013_01 - Superior Reduction of Disulfide Bonds in HDXMS
  • 210_014_01 - Metabolism of 3 New Cardiovascular Drugs
  • 210_015_01 - Electrochemical Reduction of Biopharmaceuticals

Sysem configuration

For the simulation of oxidative metabolism Antec provides a number of electrode materials that are useful for the synthesis of metabolites. A platinum, and the new Magic Diamond™ electrodes are supplied. The system further comprises of the following parts:

  • AS 110 autosampler, cool, micro
  • P6.1L HPLC pump, 2 x
  • Clarity data acquisition software ROXY
  • ROXY potentiostat DCC
  • Reactor cell with Pt, GC, Au, MD WE, and HyREF 

 

Part no Description
210.0080W ROXY EC/LC system