Hi,

Some discussions and answers are available on RG (13 links) below:

Should be helpful,

Best regards

Tomasz

Sample pKa 16 ? Rather unusual.

You are using a methanol mobile phase, on C18 column. For basic or acidic components you get a better result, with less tailing using an appropiate buffer.

Try a water / buffer mobile phase at slightly basic pH, depending on the pKa of your sample component of interest.

If using 100 percent methanol as the mobile phase for a C18 column causes peak issues, use some water or a buffer in the mobile phase.