Reducing matrix effects [Bioanalytics]

posted by Ohlbe – France, 2018-10-01 17:20 (721 d 23:21 ago) – Posting: # 19356
Views: 1,932

Dear ElMaestro,

» is there any method published anywhere which can be realistically thought to have no matrix effect?
» Not just absence of mentioned effect, but truly verified absence of one and how would one go about proving it?

Define "no matrix effect". Same as concentration = 0: truly 0, or BLQ ? No matrix effect, or negligible ? Considering the analytical variability, I would consider it strictly impossible to demonstrate 0.000 matrix effect.

» If you had a gun pointed to your head and someone asks you to develop an LC-MS/MS method without matrix effect for, say, Duloxetine or Simvastatin where would you start?

Our Father who art in heaven...

I would start with:

  1. using matrix obtained the same way as subject samples (vacutainers, not commercial plasma collected in blood collection bags full of plasticisers)
  2. a real, proper sample cleaning (SPE or LLE, with a real development to really clean up, without too much loss in recovery. For instance, MTBE usually gives you a very good recovery of your drug... but also of quite a lot of things you'd like to get rid of)
  3. a real chromatography (not a 90 seconds run on a 30 mm column)
  4. comparing APCI and ESI. APCI is supposed to be less sensitive to matrix effects. Unfortunately, it is also less sensitive, full stop. May be problematic if a very low LLOQ is required (would not work for a number of the molecules you're working on).

And that's if I limit the definition of matrix effects to differences in detector response. You could expand the definition to include differences in recovery.

Regards
Ohlbe

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