Chromatography Forum

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

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".

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

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