Reducing matrix effects [Bioanalytics]
Dear ElMaestro,
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.
Our Father who art in heaven...
I would start with:
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.
❝ 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:
- using matrix obtained the same way as subject samples (vacutainers, not commercial plasma collected in blood collection bags full of plasticisers)
- 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)
- a real chromatography (not a 90 seconds run on a 30 mm column)
- 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
Regards
Ohlbe
Complete thread:
- FDA Recommendation on Matrix Effect Determination in CC Assay Obinoscopy 2018-10-01 14:38 [Bioanalytics]
- FDA Recommendation on Matrix Effect Determination in CC Assay Ohlbe 2018-10-01 15:30
- FDA Recommendation on Matrix Effect Determination in CC Assay ElMaestro 2018-10-01 16:30
- Reducing matrix effectsOhlbe 2018-10-01 17:20
- FDA Recommendation on Matrix Effect Determination in CC Assay ElMaestro 2018-10-01 16:30
- FDA Recommendation on Matrix Effect Determination in CC Assay Ohlbe 2018-10-01 15:30