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- Posts: 22
- Joined: Tue Oct 18, 2011 12:01 pm
I have a question pertaining to the demonstration of the linearity of a method when you don't actually have a reference material for the analyte in question. I have an decent idea of what I'm going to do (which will inevitably involve a few trips to the QA department!) but always useful to ask for advice.
Some background. The method development is needed to monitor a reaction that proceeds from one compound to another (stage 1 to stage 2) via 2 intermediates. In order for successful production there must be negligible intermediate 2 in the stage 2 compound (<= 0.5%). The reference method used at the moment to monitor this is a TLC method that can be quite hit and miss and therefore we need a more accurate means of monitoring intermediate 2 to ensure that the next stage of the reaction does not proceed until we are confident int. 2 has been reduced to acceptable limits.
The challenge comes in that we don't actually have any reference material for the 2nd intermediate. Therefore my proposal is simply to obtain a sample from the reaction vessel at the point when intermediate 2 is going to be at its highest (the nature of the reaction means that there is a point in the scheme where this can be assumed) and assign this a nominal concentration of 100%. A series of dilutions can then be prepared in order to demonstrate linearity.
QA may well have some additional concerns but I thought I'd run this general idea past people on here to see if anyone has encountered this issue before and if so what they did. If not is there anything else that might improve matters.