'MURDER" or "MURTHER" ? -- Question on when distinct (archaic) spellings for words were used and when not

Salutations, I am currently writing a play that is being regulated to the very distinct notions of authentically replicating the English language and its archaic spellings during its usage in London, early 1600s. For this, I have primarily focused myself by perhaps the most illustrious of poets from the time period: being Milton with the original text of Paradise Lost and of course Shakespeare’s first and second folio. I have noticed a few peculiar spelling distinctions and differences printed in Shakespeare’s first folio. For example in page 67 of the first folio (Romeo and Juliett) the word "murder" and again a few words later as "murdered" in Romeo’s line of,
"As if that name shot from the dead levell of a Gun,
Did murder he, as that names cursed hand
Murdered her kinsman (….)" is printed with the modern-day spelling of the word (Murder).
and yet in multiples instances, an example being found on page 337 of the same first folio (Othello)
the word "murder" is spelled "murther" in the following line: "Helpe, helpe, hoa, helpe:
The Moore hath kill’d my Mistris. Murther, murther."

Just for another example, and there are quite a few of these spelling differences, of the peculiar and to what I could reconcile rather "Mindless" changes in spelling is the word "Tragedy."
Take to account how the word "tragedy" is spelled in its modern-day spelling in the first folio as "The Tragedy of Cymbeline" or even "The Tragedy of Richard the Third." And yet in the same folio, the word is altred to the archaic spelling of "tragedie" for example in the "Tragedie of Julius Cæsar" or "The Tragedie of Macbeth."

I am interested in authentcially replicating the language of the period for my play to the most fine consideration which is plausible, and so if anyone has any insight on the distinct and rather exceptionally evident changes to the same word within a single text I would profoundly appreciate it.
I know quite thoroughly the minimal distinctions in text from 1600s like the change of "spoke" to "spake" and the added -e to enunciate stress onto a word, but I am interested in knowing the more distinct changes: especially the one on the spelling of "murder" which I need for the play I am completing.
Anyways,