I am not sure I understand your question.
You might be asking about "surrogate standards" where you want Skyline to use a different molecule as the denominator when calculating ratios to standards.
Here is our help page about surrogate standards:
https://skyline.ms/wiki/home/software/Skyline/page.view?name=Surrogate%20Standards
(That's a pretty short help page. Let us know if it is difficult to understand-- it might be that we should update that page with some screenshots).
-- Nick

Hello Nick and Nay Min,

I came across this question because I have the same need for relative response factor based quantitation in skyline. I will give a short description of what I mean by this.

Relative Response Factor (RRF) is the ratio between the Response Factor of a compound and the
Response Factor of a chosen reference standard. The reference standard is often a matched isotope labelled internal standard.

RRF = RF_analyte/RF_IS

Response Factor (RF) is the ratio between the concentration of a compound and its corresponding analytical response

RF = Signal/Concentration

We determine the RF for the analyte and the internal standards in a calibration experiment to establish the RRF. We add a known concentration of internal standard to our extraction so that we can solve the RRF equation for the concentration of the analyte using the measured signal for IS and analyte.

RRF = (Signal_analyte * Concentration_IS)/Concentration_analyte * Signal_IS)

Concentration_analyte = (Signal_analyte * Concentration_IS)/(RRF * Signal_IS)

I hope this explains this approach to quantitation. I would really like to be able to do this using Skyline and would be happy to clarify further.

Thanks and regards,
Matthew