The issue with a 21 is that the slide is still a lil too light weight. If it had the mass of a 20 then 45super wouldn't beat it up.
Factory 45super will not kaboom in a glock barrel, the barrel will handle it. I fired plenty of 45super from a stock G30S with a 20lbs RSA.
I think a 19lbs RSA will be enough balance to feed 45super reliably with stock mags, adding weight to the slide will be your best bet without using a comp.
With an aftermarket barrel having a tighter chamber entrance, a 19lbs recoil or higher spring might cause ftf with some rounds and a mag spring upgrade will be needed.
460Rowland springs seem to work but I never tried one.
I tried AGP Arms springs and they are not much better
I currently have an ETS spring in my G21 mag with the same amount of coils as the original and works amazing.
With that being said, I believe the best option for a G21 with an aftermarket barrel is a threaded barrel and a small comp, so you can still fire 45acp. One port on top, i think a 2 port comp will leave 45acp too low a power factor. Also, a 14lbs recoil spring for reliability of all ammo.
I have a G30S with a KKM, 2 port comp, CDS 14lbs RSA, I haven't found any ammo from 45acp to 45super that it doesnt eat well. 230gr 45super eject to 5ft only.
The same setup on a G21 that has quite a bit heavier slide might not run 45acp well, but +p should be g2g