Help with Ramipril Assay by Normal Phase

[Wormwood]

Hi,

After working on a reverse phase method for ramipril successfully for several months now, I now find myself needing to do the same but by normal phase due to a change in sample matrix.

I've initially tried this on various ratio's of hexane:IPA but found that the peak shape was appalling, ramipril tailing massively.

Therefore I switched to Hexane:THF this gave what I took to be a ramipril peak for sample preparations but gave either a much reduced or no peak for the equivalent standard.

Any pointers on likely conditions etc would be greatly appreciated

[Uwe Neue]

I don't know if the slow rearrangement of the ramipril is also happening in normal-phase solvents, but this could be the cause of the ugly peak shape. The simplest way to improve this is to increase the temperature.

[Wormwood]

I suspect the peak shape is probably more to do with interaction with ramipril on the silica, i.e hydrogen bonding issue, which is why I tried THF.

Thanks for the suggestion though I'll give it a try