First Ever Recorded Firearm Assassination Was A DUPLEX Load in 1570:

I'm a fan of duplex loads (and 'triplex' - MULTIPLEX in fact). - I find the novelty amusing ... Hand the revolver to a shooting mate and say "Try this 327 Federal Magnum at that clean target" - and watch their face as they fire say three shots and they get SIX holes in the black.

- Very effective in bowling pin matches too with a medium power load.

10 mm Auto duplex round.

However - long before self contained cartridges - folk loaded double charges into muzzle loaders - both deliberately and accidentally..

"James Hamilton was called "of Woodhouslee" and "of Woodhouslee alias Bothwellhaugh" in the record.
 He was said to have shot Regent Moray twice in the belly and navel on 23 January 1570, with a gun loaded with two lead balls. - By his flight to France he had taken responsibility for the treason and murder."

In Scotland, 1570 - James Hamilton used his uncle's brass matchlock carbine, of 3 feet 5 inches (104 cm) overall length having a hexagonal bore barrel of 2 feet 5 inches (74 cm) length.

 The stock was inlaid with a deer feeding and at the butt had the usual covered container for storing bullets. - This is the first recorded use of a firearm to assassinate a "public figure".

The gun used - "The Bothwellhaugh Carbine" is variously described as a CARABINE , a hacquebut, and a 'caliver' - call it what you choose but the shooting was effective - fatally wounding The Earl Of Moray - "The Good Regent"  - the shot also killing a nearby horse.

23 January 1570 LINLITHGOW, Scotland.

"The Earl of Moray, the Good Regent, was slain in Linlithgow by James Hamilton of Bothwell-haugh, who shot the said Regent with a gun out at ane window, and presently thereafter fled out at the back, and leapt on a very good horse, which the Hamiltons had ready waiting for him; and, being followed speedily, after that spur and wand had failed him, he drew forth his dagger, and struck his horse behind; whitk causit the horse to leap a very broad *stank; by whitk means he escaped."  .. From a contemporary report (1570).
* A 'stank' is a pool or a pond.

There is a very detailed Wikipedia page on this historic shooting that is a good read:

https://en.wikipedia.org/wiki/James_Hamilton_(assassin)

Marty K.