Wondering if anybody has ideas about a carryover problem I have here :)
I'm injecting a mixture of moderately polar (log P -1 to -4) and weakly basic (pKa 7-9) compounds (Mwt. ~300) onto a polymeric TFC column in diluted plasma samples. Column carryover seems to be a consistent problem in the range 1-2 % but reduces slowly when I make repeated blank injections. The loading mobile phase i'm using is 10mM Ammonium Carbonate (pH 9).
After trying several washing steps such as acetic acid, trifluroacetic acid, ammonium formate, acetonitrile/acetone, 1% ammonia soln I am still having the same problems. Replacing the column eliminates carryover temporarily and performing blank injections through the autosampler but without a column removes the carryover.

Appreciate if anybody has any ideas? Due to the compound polarity I'm presuming ionic interactions are more the problem. How can these be eliminated?

Thanks

Paul