USP Copovidone Limit of Monomers Reproducibility Issues

[dfh60min]

Has anyone performed the USP Method for determining N-vinylpyrrolidone, 2-pyrrolidone and vinyl acetate in Copovidone?

A colleague of mine is having reproducibility issues and is convinced that his analytes are either selectively evaporating from sealed HPLC vials, or are reacting with the vials themselves. The first theory seems suspect to me given the vapor pressures of the analytes. Only vinyl acetate could show this behavior, but it is dissolved in diluent (water/ACN I believe), and the vials are kept in a sample chiller at 4 C.

So far, his solution to this problem is to vial the standard prior to each injection. This makes absolutely no sense to me, he takes his standard flask out of a fridge at 4C, vials it, and then places it in a sample chiller which is also at 4 C.

If anyone worked with these analytes or this specific method, please enlighten me. Is there an inherent problem with the USP Copovidone method or is this a case of operator error?

[sisay]

Same problem here, it seems that vinyl acetate is very unstable. We used vinyl acetate stablized with hydroquinone.

In my case, the peak area in diluted solution is even higher than that in its stock solution. I was wondering if any one has figured how to resolve this issue or special handling for vinyl acetate? Thank you very much.

[devilrejects]

What column do you use for the test? with the one indicated in the USP, I get very bad spikes. I work better a Waters Symetry 250 x 4.6 x 5 with a proportion of 91.5:3.5:5 (Water:ACN;Methanol) until the 14th minute.