Hi Magic Kitty,
Welcome back. Are you able to let us know what the compound and matrix is? Can I also ask if this the only compound of interest and if any of your matrix compounds are structurally similar to your analyte?
For the time being I'm going to ignore inlet parameters because I assume that your Triplus 500 plumbs straight into the column...
With a problem like this one, I would begin thinking about the key points of what I'm trying to achieve and see where this gets me. Boiling what you've said down (with a few assumption thrown in for good measure), you're attempting targeted analysis of a single compound which may be present at at trace level and you (probably) aren't remotely interested in anything else in there. This would to me at least strongly suggest (if your other compounds are dissimilar) the use of SIM based analysis which would allow you to cut some corners when it comes to method development. Because separation (in this instance) is not terribly important, your method development could focus primarily on getting your compound off the column to the MSD nice and quickly, reliably, with a decent peak shape and minimum of peak area variability.
If you are happy to use SIM (I think you mentioned it in your last post), then the first thing I would do would be to do a bit of research (using NIST) and try to ascertain what M/S fragments to expect from my compound and which are likely to be the most prevalent, most specific and give the necessary confidence that what I'm detecting is what I think it is!
I would begin by basic compound testing. I tend to make up 10PPM solutions for liquid based analysis, but as this is headspace, Motoball's suggested 100 PPM stock might be a good starting point. I would run the sample initially as TIC (possibly at a range of oven temperatures) and see what you get - method development is often a fair bit of trial and a lot of error! These initial runs should help you to confirm that your analyte is not degrading on-column under the kinds of conditions that you might be using and whether peak shape is acceptable (or not). If you get broad peaks then it may be necessary to re-focus your compound by setting a low initial oven temperature and ramping. These initial stages are where you get to know your compound and what it likes or dislikes - something a lot more important for methods where you are interested in separation and detection of multiple analytes.
I would also run some real life samples as TICs just so that I know what else is in the sample. Whilst SIM effectively masks any signal from additional compounds, I still prefer to know what comes out and when and would ideally like to create a method where my analyte is chromatographically separated from everything else. At this stage, I would check out the effectiveness of my choices of SIM ions by creating an EIC from a TIC run. This way I can get an idea as to how effective my choices are and can select different SIM ions if there are any problems.
Once you're sure all is good then you can switch to SIM selecting 3 ions that are characteristic of your compound that are hopefully abundant. Bingo, a method that works...
What about internal standards I hear you ask... Here you have a problem, especially with headspace. Ideally you want an internal standard with properties nigh on identical to that of your analyte (but which do not co-elute), which is why most people (where possible) choose deuterated target compounds. Given that no method exists for your compound, it's highly unlikely that a deuterated analog exists and I would imagine that having one synthesized would be cost prohibitive. On that basis, you might have no option other than to go down the route of standard addition if accurate quant values are important to you.