Could this situation be an interaction between stationary phase and excipient?

Hi MagicPill

More questions than answers...

Is your method isocratic or gradient?  What is the magnitude and direction is the retention time shifted?  Do the retention times return to their original values after flushing or cleaning the column?

Kind regards

Andy

Andy 

I'm running a 15 min gradient, the retention times are shifting later ~1.5 min.  The relative retention times of related impurity peaks are similar when active peak has shifted retention time.  Do flush and store column with 50% acetonitrile in water at end of analysis.  Retention Times do look to return to original values after flushing column

Hi MagicPill

Thanks for the information.

It could be that the excipients are causing the shift in retention time, with your NCE being retained by one or both of these materials (I don't know the chemical nature of these two compounds) that is being retained by the column.  I would try to increase the percentage organic at the end of the gradient, and maybe use an extended hold at this high organic percentage, to see if this makes a difference.

Does the NCE peak move a small amount after each injection?  Do they reach a steady state when they no longer move?  I assume that the NCE, in the absence of the excipients doesn't change retention time with repeated injection.

Kind regards

Andy

Hi MagicPill

Thanks for the information.

It could be that the excipients are causing the shift in retention time, with your NCE being retained by one or both of these materials (I don't know the chemical nature of these two compounds) that is being retained by the column.  I would try to increase the percentage organic at the end of the gradient, and maybe use an extended hold at this high organic percentage, to see if this makes a difference.

Does the NCE peak move a small amount after each injection?  Do they reach a steady state when they no longer move?  I assume that the NCE, in the absence of the excipients doesn't change retention time with repeated injection.

Kind regards

Andy

Andy - Pertaining to your 2nd paragraph, last sentence, yes NCE in absence of the excipients does not change RT with repeated injections.  Will try a high organic hold at end of gradient, and add a guard column.  Thank you for all of your input.