This problem is not directly related to RadSplitter but is an issue with the MS AJAX Framework and how an <iframe> is disposed. You can observe the same behavior using standard <iframe> with initially loaded a page containing scriptmanager, and then change the its SRC to load a PDF file. For your convenience I have attached a sample page demonstrating this issue.
I have logged this into our database for further investigation, and we will try to handle it (if possible) for one of the upcoming releases.
the Telerik team
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