Recently, I began work on a USP related compounds HPLC method which uses a mobile phase of 4000:1 n-hexane:ethanol. I attempted the method on a new Agilent 1100 LC. My problem is that the pump seems to be losing prime - and then sometimes re-priming itself(?). I've tried to eliminate air bubbles trapped in the system (which has an on-line degasser). It's been a long time since I've had to conduct normal phase chromatography, but I don't seem to remember running into this problem. Any help would be appreciated.

do you observe pressure drops? if so, a reason may be the valve. hexane and heptane may lead to electrostatic charge of the globes inside the valves. some manufacturers hint this in the handbook

Remember to purge all four channels 5ml/min for 5 minutes each, even if you're only using one channel in your assay.

Haven't used the Agilent system but we also had problems switching between RP and NP modes on a Shimadzu system. One of the problems was the pump seals would tend to leak when the solvents were changed. Since the NP solvents are very volatile, this was not always readily apparent. The Shimadzu system also has a solvent compressability function that needed to be changed for NP solvents.

You’ve probably already done this but I have found placing the solvent bottles well above the pump tends to reduce the losing of a prime. Most pumps perform better through a gravitational feed, i.e. the solvents can drop down to the pump head.