PharmPK Discussion - Reactive Metabolite

• On 24 Oct 2009 at 20:29:53, rahul vats (rahulvats1983.-a-.gmail.com) sent the message
  

  
  Dear all,
  
  I would like to know about reactive metabolite/parent compound per say
  conformation assays with GSH for high through put screening. These
  kind of reactive metabolite-GSH formation are Phase-ii conjugation or
  different?
  
  Thanks in advance
  Regards,
  Rahul Vats
  
  

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• On 26 Oct 2009 at 20:28:00, Wanli Li (wanlisci.at.yahoo.com) sent the message
  

  
  Hi Rahul,
  
  GSH is considered ph II conjugation. But due to its nucleophilic
  property that will usually bind to reactive metabolites only, the
  study of GSH-conjugation is then used more to understand ph I
  oxidation mechanism.
  
  Hope this help.
  Li
  
  

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• On 27 Oct 2009 at 10:15:31, Sagnik Chatterjee (sagnik.chatterjee.at.gmail.com) sent the message
  

  
  Hi all,
  Just to add to Li, GSH conjugation can also be used to check reactive
  acyl glucuronides, like diclofenac glucuronide. If you incubate the
  acyl glucuronide in microsomes with GSH and if the acyl glucuronide is
  reactive it will also show glutathione conjugates.
  Diclofenac hydroxylated metabolites show glutathion conjugated peak at
  m/z 617; while the S Glutathione, coming from the acyl glucuronide
  show peak at m/z 585.
  Hope this helps
  With regards
  Sagnik
  --
  Correcting myself,
  The reactive acyl glucuronide may not always show GSH conjugation,
  specially in in vitro condition, its not 100% predictive of tox due to
  reactive metabolites.
  With regards
  Sagnik
  
  

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