My opener is usually something cute, funny and references her profile which ultimately qualifies(shows her why I messaged her). However I find around 1/5 of responses are "Are you joking/being sarcastic?". I've experimented with various ways of trying to turn the interaction around from there.. but messages tend to die shortly after.

I'm interested to hear some ways you guys would suggest in order to turn things around when a girl seems to assume the comment is disingenuous or sarcastic?

I'll use the ideas and split test them to see which method is most effective.

your opener sucks, they are responding so u are doing something right on your profile

give me examples of your openers?

You're getting first responses so that's a good thing. But to get second and third responses and ultimately the phone number, you have to move it along. Think of the stacks that you use in a bar or in day game, then refine those stacks for online. For instance, in a bar you might use a good neg, but it works because your body language shows the girl that you're teasing. If you use that same neg online, without a way to show her what you mean, you will probably lose her.
When I started online game ten years ago, there were vey few books or blogs that told me anything about how to get women online. I had to learn myself. I finally came up with a good stack that I use and get a lot of dates off of, and I'm not a good-looking guy at all. Most of these dates are HB8's, but occasionally I will get a 9, and once in awhile a 10.
Use trial and error. Remember, there are thousands of women online to practice with.