Using methanol/water/1% acetic acid, and YMC Basic or ODS-A columns (3 x 250 mm with guard columns), I have great peaks for 10-20 runs, and then late retention times and broad peaks for all glucuronide metabolites.
Curiously, other peaks remain sharp and elute at the correct retention times. Cleaning the column with THF and MeCl2 restores the column temporarily. The sample (from urine) is cleaned-up on C18 (Bakerbond) XAD-2, and SCX resin before injection. Any ideas what is happening and improving the longevity of my system?