Depends on what that protocol is!
The general approach will be the same (get retention first, then focus on selectivity, finally tweak efficiency as necessary). Specific differences will include:
- - the resolution requirements for LC-MS are generally less stringent than for LC-UV
- mobile phase buffers/additives, etc. must be volatile and compatible with the ionization technique used
- mobile phase flow is typically restricted by the need to vaporize the solvent (hence smaller columns and lower flow rates)
- smaller columns mean smaller injection volumes and the need to be more careful about extra-column volume generally.