Acetaminophen/paracetamol quantification

[annaand]

Hi,
I am working with acetaminophen, or paracetamol as you wish.
I know you think - trivial analysis. I thought so as well. But it makes me crazy.
I have to quantify the amount of it in tablets. I started with reproducing a method that I found in literature with use of pure acetaminophen (no excipients). I cannot exactly reproduce the conditions, usually my column is different from what they used. But not radically different (always RP, C8 vs C18). I have tried many different methods and I came across the same problem (what I think is a problem but please correct me if I'm wrong here). The retention time of the acetaminophen is always very small, practically equal to dead time. Now there is my question:
Is it ok to use such a method for quantification of analyte when it is almost not retained? Is it reasonable? I have seen papers published with method development for acetaminophen + other compounds (e.g. caffeine) where peak of acataminophen is very close to injection peak or even on it.
Of course I have played with mobile phase composition going down with organic phase to have it retained longer. But then the peak starts to have crazy shapes.
Any advice?
Thanks,
Anna

[tom jupille]

To answer your first question, no, it is not a good idea to try quantitating a very weakly retained compound. The FDA's Guidance for Reviewers suggests that k' values should be > 2.

I'll throw out the suggestion that it may be more cost-effective to simply get the original column rather than spend a lot of time trying to "reinvent the wheel".

[Uwe Neue]

Here is an application for you that contains the compounds that you mentioned with very good retention:
http://www.waters.com/webassets/cms/lib ... a60217.pdf

[annaand]

Thanks guys for help! I'll try your suggestions.