Hi,
I need to know the effect of a solution of PEG300(30-40%)in 5%dextrose (used to dissolve the drug of interest) on the general chromatography (elution and detection). The column used is a C-18 (mobile phase: Methanol and Water) and the detector is set at 240nm. The volume of injection is suppose to be 20 or 50uL. If someone can share some experience with me...
Thanks

Why should it have an effect?

My experience using PEG overtime is that it will coat the silanol groups and cause the chromatography to go to hell. I know of several pharma-type companies which use PEG in enzyme reactions that only get 20-40 injections on their columns before they get totally coated and become useless.

I don't know about that. PEG at this molecular weight can be washed off a column fairly easily, if it adsorbs at all. In addition, most people don't like the silanols anyway....
I would appreciate a more detailed description of the situation that you interpreted as being a problem caused by PEG.

My idea is, that use PEG solution as sample solvent is to avoid peak doubling. That can occur when sample solvent is too strong (methanol % higher than at start of analysis) or injection volume too high (50ul is enough high for 4,6mm column diameter).
For example: to determine impurities at ppm level I dissolve 10% of Bisphenol A in ethylene glycol instead of methanol.
(If your drug sample can be diluted by pure water, all over is no matter).

First thing to try to prevent column failure might be:

1. Use a guard column and replace as needed.
2. This is conjecture so take it for what it is worth.

A waxy substance like PEG will not migrate well on a Reverse Phase support due to low solubility. The waxy buildup will then act like a normal phase surface to a degree, and could certainly cause broad and unfocused sample plugs at the head of the column when samples are injected, thus destroying the separation of analytes desired.
If a solvent system could be used to remove this 'waxy buildup', preferably "backflushing" the column, then column perfermance might be restored.
The obvious thing to try would be to test a short guard column alone (two simple and widely separated analytes) and see how many injections will cause the separation to fail. Then try to remove the PEG buildup and restore the separation.