I killed that behemoth of a water buffalo with a .450 Marlin after extensive bullet and load testing. It was 2500 lbs worth. Got charged twice and narrowly escaped having to shoot the two that charged. There was a doctor there when I killed it that had killed 5 cape buffalo and 3 water buffalo. He took quite and interest in the autopsy. He said he had never seen a cape buffalo close to the size of this critter. The load basically duplicated the power of a .500 S&W or right at 3000 ft lbs. I chased the devils for 4 hours before I ever got a good shot opportunity. They were wilder than deer. When I finally got a shot it was trotting at 50 yards. The bullet broke the onside front leg bone and penetrated through the lungs into the offside shoulder breaking it and stopping the beast. They said they had never seen anyone take one shot and dump one. I put a safety shot in it but it wasn't needed. I left a .416 Rigby that was my back up gun behind that with its +p loads was making 7000ftlbs. Would it have done anything that the .450 didn't do? Fact is if you can put a bullet through the stuff that makes it live its going to die.
To put this in perspective the horns are 27" wide. We measured it with the leg extended as if standing. This thing was 6' tall at the shoulder.