Absolutely. This was an early requirement for Skyline, because the funding organization, CPTAC, wanted to do this in their experiments as well. You can find Skyline documents with their examples here:
The 9.2 experiments used both 15N12C-Arg/Lys and all-15N labeled peptides.
Just quickly, when you drop the "Isotope label type" list, you can see an "<Edit list...>" option. You use that option to add label types to the default "heavy".
There is also a webinar on working with modifications in Skyline:
This case and the CPTAC data are presented around 51 minutes.
Hope this helps. Thanks for posting this question to the Skyline support board.