While the interaction makes sense currently as far as wording goes, it doesn't as far as balance/gameplay goes.
How does it work:
If you Whoopaz a zotted enemy, you take him down to half his total health. This means that you can take any boss down to 3/8 health with any character with just a click or two.
What does it translate to:
It translates to having a bit over 2 stacking whoopazes which you can apply on a single hit.
What does that mean:
It means that the restriction on being able to prep only one whoopaz loses meaning. It also means that the Orb of Zot drastically changes it's wording in regards to whether you have a whoopaz handy or not - from "take a boss down to half health permanently by regen fighting him easily" to "take a boss down to half health permanently in 2 clicks"
Why does this not make sense:
1) Zot is powerful on it's own, but this use is strictly better - zot allows you to take away half the health on a boss with less effort than usual, this allows someone to take away half the bossess health with no effort at all.
2) Whoopaz is restricted, in most cases, to one per run. It's powerful, and completely universal, meaning that anyone at all can prep it and the dodge potion and have a brutal first hit on a boss. This allows you to have an even more brutal first hit which translates to having 2 permanent whoopases.
3) It makes Zot a much better prep than find. If you don't have whoopaz it's merely powerful. If you do have whoopaz, which can only be prepped, it's the most ridiculous thing there's ever been in the game (including "let's leave it in, lol" stuff like Titan Guitar). Seeing that Zot costs 50 gold to buy, purchasing it is actually a very significant choice to make in a dungeon run, while prepping it only affects your kingdom gold.
4) The paradox under 3. leads to having a really easy time developing a habit of prepping Zot. It's good for leveling, it's regular effect is good AND it makes killing the most dangerous boss half as easy.
Suggesstion:
So I'd repeat Sidesteppers (or someones) good suggestion of having whoopaz work on current health rather than total health. I'm not sure if it would mess something else up, but I'm sure it would also help with the problem of whoopaz being useless unless you use it on the first hit, and even vets forget and have it sit in their inventory for no reason.
EDIT:
Just to make sure noone thinks I'm being a self-righteous killjoy of some sort, it's not that I don't see potential arguments for "leave it in":
Q: It's fun, there's other powerful stuff, why this?
A: Because it's fun in a "look ma, no gameplay!" way. It's too good to kick it out of a locker slot, and it's too strong not to have you considering it every time you play. It's also a class-race-deity-strat unrelated bosskiller gimmick, in a game where killing the boss is how you know you won. Both elements are really strong on their own, and Zot is actually a fine, if overpriced, leveling prep even if you neve "pop" it. This way you don't have to pop it untill the boss fight, when the fine leveling tool translates into a half-dead boss in a jiffy.
Q: But how do we get out monster classess now?
A: By using races, classess, glyhs, blackspace, strategy, gods, items... items including even the Orb of Zot, which starts you off with some health and mana and lets you regen fight a boss for unlimited poison strike untill he's at half health. Just saying.
EDIT 2:
A fun suggestion I just had a thought that considering the pricyness of the Orb of Zot, that maybe it could apply it's effect at the time of purchase as well as being able to self sacrifice for reinforcing it? A-la Titans Guitar. Might be a good idea, since the big "meaninful choice" moment is when you decide to dish out the big pile of gold for it or prep it - destroying it jusg gives you what you payed for and opens up a large inventory slot. Might be worth a thought.