PharmPK Discussion - LC-MS-MS instrument differences

• On 23 Oct 2007 at 09:34:53, Tai Ly (twly911.at.yahoo.ca) sent the message
  

  
  Dear All,
  
  We are in the process of deciding on purchase of a lc/ms or lc/ms/ms
  instrument for metabolite screening/profiling.  Can anyone please
  elaborate on the advantages of a TOF vs. triple quad instrument?  I
  remember reading somewhere that tof is more sensitive?
  
  thanks in advance,
  
  Tai Wei
  
  

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• On 23 Oct 2007 at 22:03:39, "Stefan Soback" (stefan.soback.-at-.gmail.com) sent the message
  

  
  I'm not a TOF person, but I hope the following will help. TOF gives
  you a very accurate mass of your analyte (about 5 decimal places).
  Usually there are very few combinations of atoms that can produce
  that molecular weight. You did not describe what kind of TOF you are
  looking at. You a also buy a MS/MS TOF.
  
  I doubt that TOF would be more sensitive than a [good] triple quad.
  Today you can buy also a triple quad with linear ion trap in the end
  enabling MS/MS/MS operation. In a 3D [conventional] ion trap you can
  do as many MS steps as you like (but loosing sensitivity on every step).
  
  Stefan
  
  

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• On 23 Oct 2007 at 17:39:19, Stuart Coleman (stuart.coleman.-a-.matrixbioanalytical.com) sent the message
  

  
  The following message was posted to: PharmPK
  
  Tai,
  
  A quadrupole-TOF configuration is often used for metabolite ID. The
  front part of the quadrupole-TOF instrument has an electrospray or
  APCI type source, just like a triple quad. The TOF section of a
  quadrupole-TOF instrument provides accurate mass mesurement, so
  they're good for "picking apart" a molecule, and getting a pretty
  good molecular formula for the pieces.
  
  There's another instrument on the market now that's great for
  metabolite ID and profiling - the LTQ-Orbitrap from Thermo.  It seems
  to be taking over the Metabolite ID/Profiling market.  It provides
  high sensitivity, high speed analysis, MSn capability, all combined
  with an LC front end.  Mark Sanders' group at BMS has several good
  publications out covering methods using this technology.  It's pretty
  expensive though.
  
  At the end of the day, you'll want to stay away from any kind of TOF
  instrument for quantitation, (in my opinion).  Triple Quad
  instruments are still the gold standard for quantitation.  Richard
  King at Merck has published some excellent work using a TOF source
  for rapid, early discovery quantitative analysis.  But TOF is still
  not there yet for reliable quantitation - regardless of sensitivity,
  (again my opinion - others might differ).
  
  The 4000 Q-Trap from Sciex might be a good compromise.  It's good for
  metabolite ID and profiling (sans accurate mass), and may also be
  used, with the Trap turned off as an API-4000, (one of the best
  triple quads for quantitation).
  
  Best regards,
  
  --
  Stuart Coleman, Manager
  Matrix BioAnalytical Laboratories
  25 Science Park at Yale
  New Haven, CT  06511
  Phone:  203.789.1800
  FAX:       203.789.6123
  Cell:  203.606.2218
  Web:  www.matrixbioanalytical.com
  Email:  stuart.coleman.-a-.matrixbioanalytical.com
  
  

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