Currently have an issue with lack of sensitivity in a particularly steep RP gradient HPLC method. What are the options for resolving this? Is the use of masking agents recommended? Would acetophenone be acceptable for this application?

Thank you.

Need more information here (assuming reversed-phase LC with UV detection):
- what wavelength are you using for detection?
- what is your organic solvent?
- is your problem caused by baseline drift during the gradient?

If you're using low-wavelength UV and the problem is UV mismatch on the solvents then, yes, the addition of a UV-absorbing agent to the A solvent can help. Ideally, you want something that doesn't stick to the column, so something like nitrate ion would be a good choice.