Everyone knows you can't just kill Svetka Ignatyeva.

If you try to shoot her, she'll shoot the gun out of your hand first.  If you try to take her in single combat, even if you're the second best in the world, you may succeed in fighting her for a minute or two, but it will end with you going down, or escaping, or at best her getting distracted and going off to do something more urgent.  If you try to gang up on her it'll go even worse.  This is the way of things: being the best in the world at something is vastly, vastly better than being the second best.

But, if you really wanted her dead, and were an organization with a lot of resources and human capital, you might... nuke the city she's in?  No, she'll turn out not have been there, and then you'll also be trying to nuke a city and people basically never succeed at that.  No, what you do is you separate out the steps.  People have sometimes managed to nick her, not with a real poison and not if they were going to shoot her directly in the head once she was incapacitated, but with gentler drugs or with naked blades that let a line of blood drip dramatically down her face.

Somebody develops a drug that makes you - not quickly, but over weeks and months - somewhat more inclined to depression, or something like it.  A little more hopeless, a little harder to motivate, a little more reckless when it comes to personal risk.  Ultimately, with work as dangerous as this, that's all it takes.  You can't kill the best spy in the world, but you can make them not the best spy in the world anymore.